key: cord-0007004-29epobv1
authors: nan
title: Second Meeting of West European Societies of Biological Psychiatry Psychiatric Challenges throughout the Life Span 13–15 December 2007 – Strasbourg, France
date: 2007-11-21
journal: Eur Arch Psychiatry Clin Neurosci
DOI: 10.1007/s00406-007-2000-z
sha: baf08696248af9c9de66c6c20d854245f896dff0
doc_id: 7004
cord_uid: 29epobv1

nan

It is our distinct pleasure to welcome you to the Second Meeting of West European Societies of Biological Psychiatry, taking place on December 13-15 in Strasbourg, France. The Second Meeting of West European Societies of Biological Psychiatry is organised by the three founding countries, Belgium, France and Germany. Other West European countries will join us to support the Meeting: we are really happy to welcome our colleagues from Switzerland and Austria to Strasbourg. We are also pleased to announce that the World Federation of Societies of Biological Psychiatry again supports our Meeting. Like in human history, mutations and transitions are commonly seen by each of us on the path of our lives. Today we have a better knowledge of how much psychiatric disorders have their origin in continuous or repeated phenomena and how much continuous psychological modifications could influence and impact on the general course of psychiatric disorders.

Adult disorders are often preceded by a prodromal state in childhood or adolescence. Childhood disorders display distinct features when the patient becomes an adult.

Disorders in the elderly could result from preceding diseases or display mild signs a long time before the diagnosis is established.

Many of the best European clinicians and searchers will give us their most recent data and comments, the new advances and the future perspectives of the various processes which influence the human being and their psychiatric diseases through their life span.

Apart from the magnificence of the city of Strasbourg and the magic Christmas period, 3 main lectures, 17 symposia, 3 industry satellite symposia, 4 free communication sessions and a large poster session are offered to the participants. Cognitive deficits are now considered to be core symptoms of patients suffering from schizophrenia to such a general extent that virtually all cognitive functions are regarded as defective. However, cognitive functions are not equally disturbed. Recent meta-analyses and reviews of cognitive impairments in schizophrenia have consistently shown that, along with attention and executive functions, episodic memory is particularly impaired. Episodic memory is itself a complex cognitive function, however, and it is necessary to differentiate between its intact and impaired aspects. A better understanding of the functional mechanisms underlying the episodic memory dysfunction in schizophrenia is a prerequisite for unraveling its neural correlates in neuroimaging studies and, more generally, for developing an integrated approach to the pathophysiology of schizophrenia. It is also crucial for developing cognitive remediation. Empirical evidence of episodic memory dysfunction in schizophrenia will be reviewed, with reference to various theoretical models of episodic memory. All the studies converge to show a significant impairment of episodic memory, which is impaired in its critical feature, conscious recollection. They also show a defect of autobiographical memory and associated conscious recollection. The episodic memory dysfunction results from a predominant failure of strategic processing at encoding, although an impairment of strategic processing at retrieval cannot be ruled out. The possibility that it is not the execution of the encoding strategies that is defective, but their self-initiation by the patients is plausible. These findings may explain some behavioral abnormalities associated with schizophrenia, notably inadequate functional outcomes in everyday life. They may have also implications for cognitive remediation and better social and work functioning of patients with schizophrenia. In a prospective-longitudinal study maternal anxiety was measured at 12-22, 23-32 and 32-40 weeks of pregnancy, with the State Trait Anxiety Inventory. 72 firstborns of 86 mothers, recruited at the Obstetrical and Gynecological Board consultations of a University Hospital were followed up to age 8-9, and 58 up to age 14-15. At the age of 8-9 hierarchical multiple regression analyses showed that maternal state anxiety during pregnancy explained 9% of the variance in self-reported anxiety, as measured with the State Trait Anxiety Inventory for Children. Effects remained when controlling for child's gender, parents' educational level, smoking during pregnancy, birth weight and postnatal maternal anxiety. At the age of 14-15, HPA-axis function was measured through establishing a saliva day-time cortisol profile (shortened version); during a week-end day 3 saliva samples were provided, namely immediately after awakening, at noon and in the evening. Severity of depressive symptoms was measured with the Children's Depression Inventory. We tested the following two hypotheses: (a) that maternal anxiety during pregnancy predicts altered HPA axis function (e.g., a flattened cortisol profile) in the adolescent offspring; (b) that altered HPA axis function mediates the association between prenatal maternal anxiety and depressive symptoms in these adolescents. Repeated measurements regression analysis and ordinary least-squares regression analyses indicated that maternal anxiety at 12-22 weeks of pregnancy was in female and male offspring associated with a diurnal cortisol profile that was attenuated due to elevated cortisol secretion in the evening. Moreover, in female adolescents this flattened cortisol curve was associated with depressive symptoms. Effects remained when controlling for covariates such as smoking during pregnancy, birth weight, obstetric risk, postnatal maternal anxiety and Tanner puberty phase. Our results indicate that maternal anxiety during pregnancy enhances neurobiological vulnerability to depressive symptoms, possibly by altering (or 'programming') foetal physiology. They also demonstrate the mediating role of HPA axis dysregulation in linking an adverse foetal environment to depressed mood.

If our results can be replicated in future research they may lead to a re-orientation of the target of primary prevention and treatment of anxiety symptoms in childhood and depressive symptoms in adolescence.

GLUCOCORTICOID AND MINERALOCORTICOID RECEPTOR GENE VARIANTS ARE ASSOCIATED WITH ACTH, CORTISOL AND CARDIO-VASCULAR RESPONSES TO PSYCHOSOCIAL STRESS Wüst S. 1 , Kumsta R. 1 In response to stress, a wide spectrum of adaptive responses is triggered, including an activation of the hypothalamus-pituitaryadrenal (HPA) axis. Chronic alterations in HPA axis regulation have been implicated in the susceptibility for several pathologies including depression and cardiovascular disease (CVD).

In two independent samples we investigated if common variants of the mineralocorticoid (MR) and the glucocorticoid (GR) receptor genes modulate HPA axis activity and here we focus on ACTH and cortisol responses to challenge.

In a cohort of 110 healthy males, carriers of the minor allele of the MR gene variant I180V showed higher salivary and total cortisol as well as heart rate responses (all P<0.05 ) to the Trier Social Stress Test (TSST) than non-carriers. In a sample of 206 healthy males and females we assessed four GR gene polymorphisms (ER22/23EK, N363S, BclI, 9beta). Male 9beta AG carriers displayed the highest ACTH and total cortisol levels after TSST exposure, while male BclI GG carriers showed diminished responses (P<.05 for ACTH). Remarkably, the BclI GG genotype in women was associated with the highest total cortisol TSST responses, resulting in a significant sex by genotype interaction (P<.05). Following the dexamethasone suppression test, only male 9beta AG carriers had elevated ACTH levels (sex by genotype interaction P<.05).

Our data suggest, for the first time, an association between an MR gene variant and HPA axis as well as cardiovascular responses to psychosocial challenge. This finding supports the view that the MR is substantially involved in the regulation of acute stress responses. GR gene polymorphisms have previously been associated with both depression as well as CVD. The present findings further document a significant association between GR gene polymorphisms and HPA axis regulation and they suggest a sex specific impact on responses to psychosocial stress as well as on GC sensitivity.

towards HPA axis dysfunction. A number of functional candidate genes such as the CRH receptor 1 and the AVP receptor 1b have been investigated, and converging evidence from animal and human studies suggests a role in the vulnerability for MDD. Recently, the glucocorticoid receptor (GR) has been the focus of attention. GR downregulation could explain the relative deficiency of the negative feedback regulation of the HPA axis seen in MDD. Mice with a genetically reduced GR expression exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression (1) . Similar to MDD patients, these mice have a disinhibited HPA system and a pathological dexamethasone/corticotropin-releasing hormone test. In the human GR gene, several polymorphisms have been described that alter the function or the expression of the gene. Recently, two independent publications found evidence for association between MDD and GR polymorphisms (2, 3) . While the genetic association findings in MDD are still to be considered preliminary and awaiting confirmation, the overall evidence for the involvement of the human GR gene in the pathophysiology of MDD is becoming more consistent. Post-traumatic stress disorder (PTSD) is a stress-related disorder caused by traumatic experience. PTSD is characterized by structural changes in many brain regions (including the hippocampus) associated with persistent cognitive intrusions, avoidance and arousal. Most people recover from these structural changes and symptoms following psychotherapy and/or pharmacotherapy. However, this recovery is followed by relapse within months after the end of treatment, in about 40% of cases. Today, only continuation of medication (with mainly antidepressants) beyond symptom elimination is known to improve hippocampal functioning and to prevent PTSD relapse. Given the potential link between hippocampal functioning and PTSD relapse, we have hypothesized that hippocampal high-frequency stimulation, known to increase synaptic efficacy in hippocampal outputs, would prevent symptom recovery in animal models of fear return. We found that fear extinction in rats was followed by potentiation of synaptic efficacy in hippocampal-medial prefrontal cortex outputs. In our first model (based on artificial induction) of fear return, we observed that suppression of this potentiation with hippocampal low-frequency stimulation provoked the recovery of the extinguished fear during the retention test of extinction. In our second model (based on behavioral induction) of fear return, we found that rats submitted to a chronic mild stress procedure before fear conditioning failed to develop potentiation of hippocampal-medial prefrontal cortex synaptic efficacy following extinction, and displayed fear return during the retention test of extinction. Finally, hippocampal highfrequency stimulation restored potentiation of hippocampalmedial prefrontal cortex synaptic efficacy and prevented fear recovery. These data suggest that a loss of potentiation of synaptic efficacy in hippocampal outputs constitutes a potential key mechanism of PTSD relapse. A brain stimulation that increases hippocampal activity following termination of PTSD treatment may therefore reduce risk of PTSD relapse.

Otte G.E. A. P.C. Dr. Guislain, Dept. of Neurophysiology, Gent, Belgium Cognitive evoked potentials are well suited to capture the fast dynamics of cortical generators within the narrow time window of 1-800 msec. As such, their role in clinical psychiatry is very promising both on a diagnostic and a therapeutic level. Yet to be successful, their variance has to be contained by rigid adherence to basic standard evaluation and test protocols underpinned, as far as the practitioner is concerned, by an in-depth knowledge of technical, signal analytic and clinical psychophysiological principles and insights, all forged by hands-on training and study. Specific aspects of averager technology are discussed in the light of those ERP dynamics (peaks versus components) and sources of variance in stimulus response time interval and its effect on global averages are specifically mentioned. A tool bag of novel techniques that has been developed recently should be ported to the clinical daily workplace in order to push the temporospatial resolution of the qEEG-ERP as a multifunctional probe in cognitive and affective brain (dys)function. This is illustrated with some examples. It is concluded that those developments in clinical psychophysiology are about to open up a set of new windows on the brain with special emphasis on their power to identify consistent endophenotypes in several psychiatric pathological entities. The actual consensus about some of those clinico-physiological correlations is presented to the general practitioner who needs to overview those elements at the glimpse of an eye.

TMS AND MOOD EFFECT: BRAIN IMAGING IN 'NORMALS' Baeken C. Dept . of Psychiatry, University Hospital, Free University of Brussels (VUB) Brussels, Belgium

Repetitive Transcranial Magnetic Stimulation (rTMS) is currently used as an experimental tool to investigate neurocognitive processes in healthy volunteers and to treat affective disorders. rTMS, performed mostly on the left dorsolateral prefrontal cortex (DLPFC), has yielded divergent results and effects on mood seem to be different between healthy and depressed subjects. In all studies reporting positive results on depression, rTMS treatment was spread over a period of two weeks or more, on a daily basis. Some, but not all previous 'healthy volunteer' studies, reported a mild transient increase in self-rated sadness after a single rTMS session. More recent studies, using larger sham-controlled volunteer samples failed to replicate these findings. Although subjectively experienced mood constitutes an important output of emotion, it gives only limited insight into the neurocircuitry of emotion: Emotionally generated physiological responses (e.g. stress hormones, such as cortisol) or brain reactions to visual stimuli (e.g. emotional pictures) might operate independently of verbal reports and might provide the opportunity to track psychological events in real time.

Previous healthy volunteer studies have tried to integrate and/or combine functional brain imaging to elucidate this important question of opposite mood effects in depressed and non depressed subjects. In this symposium, rTMS effects on mood in healthy subjects will be discussed. Own preliminary brain imaging data of healthy females in combination with High-Frequency-rTMS will be presented.

TMS AND DEPRESSIVE DISORDERS: INDICATIONS? Poulet E., D'Amato T. Université Lyon, EA4166, Centre Hospitalier Le Vinatier, Bron, France Repetitive Transcranial Magnetic Stimulation (rTMS) is a new promising tool in psychiatry as demonstrated by the growing body of literature since its first use in depression in 1993. In a brief description of the literature, we will examine the large number of treatment variables which could explain the range in response rates: the choice of stimulation parameters, the indistinct site of stimulation; the usefulness of neuronavigation, rTMS as an Add-on therapy, the adequate sham technique, and the better indication. Several meta-analyses examined the antidepressant efficacy of rTMS and found evidence for statistical benefits but the clinical interest remain limited. Last year the first multicentric study with large sample and without antidepressive medication which compared rTMS and placebo in depressive patients was published: results are in accordance with previous works with standardized criteria. The authors showed a significant effect of rTMS compared to placebo after 30 sessions using high frequency to the left dorso lateral prefrontal cortex. Also they used very higher parameters than in previous publications; they obtained only a moderate effect. Moreover, one important question concerns laterality and frequency: should we treat our patients with low or high frequency to the right or the left dorso lateral cortex? Others works are needed before publishing recommendations for the use of rTMS in major depression. For this purpose, we develop at present a French multicentric blinded sham controlled study with the aim to answer questions regarding the utility of rTMS in depression.

Höppner J. 1 , Buchmann J. 2 1 Dept. and Outpatient Dept. for Psychiatry and Psychotherapy; 2 Dept. of Child and Adolescent Psychiatry, Neurology, Psychosomatics and Psychotherapy Centre of Nerve Diseases, University of Rostock, Germany

Motor system excitability can be investigated in vivo by means of single and paired pulse transcranial magnetic stimulation (TMS). Several TMS-paradigms reflect inhibitory or facilitatory mechanism in the motor cortex: 1. cortical silent period (CSP) the general degree of inhibitory mechanisms within the sensorimotor loop, 2. intra-cortical inhibition (ICI) and facilitation (ICF) the excitability within one motor cortex and 3. ipsilateral silent period (ISP) the inhibitory mechanism between both motor cortices. Hyperactivity is one of the most outstanding symptom of ADHD, it seems to be reduced in adults. In childhood several dysfunctional patterns of motor system excitability could be demonstrated by TMS experiments. Such investigations were not published for adult ADHD patients. We investigated 21 adults with ADHD without psychiatric comorbidity and without any neurological disorders and compared them with an age-and sex-matched control group (single-pulse TMS: CSP, ISP; paired-pulse TMS: ICI, ICF). Correlations with clinical characteristics (subscores of the CAARS) were analyzed. The investigation was repeated after a stable dose of MPH. While ICI and ICF were not significantly changed in patients, ISP findings showed a decreased duration, whereas the latency was not different to that of normal subjects. The shortened duration was negatively correlated with the CAARS subscore for hyperactivity. These results are in contrast to the recently published data in ADHD children, which described a decrease of ISP duration as well as prolongation of latency and a normalization of both parameters after an intake of a stable dosage of MPH. MPH improved the remaining impaired ISP (shortened duration) in our ADHD adults, too. These data suggest that ISP could be understood as a solid neurobiological characteristic of deficient inhibitory motor control in ADHS as well in child as also in adulthood. It seems to normalize partially during transition into adulthood, probably due to a normalization of an underlying maturation deficit on synaptic level. Since MPH as an indirect dopamine agonist improve these inhibitory mechanisms, the role of dopamine and the dopamine-hypothesis is to be particularly discussed. PROJECT Desplenter F. 1 , Laekeman G. 1 , Demyttenaere K. 2 , VZA-Psychiatry group 3 , Simoens S. 1 1 Research Centre for Pharmaceutical Care and Pharmaco-Economics, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Leuven; 2 University Hospital Leuven, Dept. of Psychiatry, Leuven; 3 Psychiatric Hospital Sint Jan, Eeklo, Belgium As pharmacological treatment plays an important role in the treatment of mentally ill patients, patients should be informed about their medication to make successful treatment possible.

Moreover, informing patients on their medication is a patient right. Several questions on the topic of drug information will be addressed in this lecture which focuses on patients with major depression admitted to a psychiatric hospital. First, what is the impact of educational interventions about medicines for psychiatric patients on adherence, knowledge, economic, clinical and humanistic outcomes? Conclusions of a literature review will be discussed as a background. Second, what does current information provision on antidepressants to patients admitted to a psychiatric hospital look like? Experiences of health care professionals (n=34) and patients (n=9) of eight Flemish psychiatric hospitals were explored by semi-structured interviews on the topics of allocation, approach, report to the interdisciplinary team and overall satisfaction of current practice.

Third, how do patients feel about a patient information leaflet on SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants? The leaflet is designed by the Association of Hospital Pharmacists, division of psychiatry. In this study, 96 patients (from seven Flemish psychiatric hospitals) with diagnosis of major depression and a prescription for a SSRI antidepressant evaluated the leaflet on comprehensibility, utility and design quality using the consumer information rating form (CIRF).

Fourth, is differentiation of the provision of information based on the information need of the patient beneficial? A brief overview of the design and some preliminary results of the GIPPOZ-study (Dutch acronym, Differentiated Information for Psychiatric Patients at Hospital Discharge) will be illustrated. Suggestions for improving practice and further research will be given based on the studies illustrated in this lecture.

Theses methods institute a professional dialog between health professionals, leading sometimes to refine or revalue treatments. Moreover, such methods can reinforce confidences in the staff and underline the importance of the clinical pharmacist's role.

« Réseau PIC » a professional association established by psychiatric pharmacists, proposes different implementations: -an information guideline; -leaflets about psychoactive drugs, provided to patients during sessions; -a website ''reseaupic.info'' with a forum discussion and F. A.Q.; -local meetings organised by establishments and associations.

Introduction and Objectives: The growing availability of psychopharmacological agents has made the treatment options for psychiatric patients very complex and has increased the risk for medication errors. The literature on adverse drug events in mental health settings however, is very scarce. The aim of this study was to provide data on the frequency and nature of drug-drug interactions in medication records of psychiatric in-patients and to determine whether computer-assisted monitoring of drug interactions may improve the quality of drug prescribing and dispensing.

Patients and Methods: Medication profiles from 455 patients out of 4 different psychiatric hospitals in Belgium (2 with and 2 without automated interaction detection system) were screened for drug-drug interactions using Delphi, a computerized interaction detection system, and classified according to their potential harm. Opinions and expectations of psychiatrists and hospital pharmacists, concerning the monitoring of drug-drug interactions, were questioned in semi-structured interviews.

Results and Discussion: Drug-drug interactions were found in 49.2% of the medication profiles. No statistical difference in the total number of interactions between hospitals with and without computerized interaction detection system, could be found. 49 .6% of the cases concerns interactions between two psychopharmacological agents; in 25.5% of the cases, none of the drugs is related to psychiatry. Delphi classified 10 interactions as 'very severe'. In 6 of these cases, the major risk factor is a potential prolongation of the QT-interval. Literature searches revealed that the scientific evidence for the detected interactions is not always well established and that the rating of the severity may vary according to the source of information.

Psychiatrists and pharmacists indicated that monitoring of drug-drug interactions is very important, but confirmed that no protocols or management plans have been implemented.

Conclusion: This study shows that about half of the psychiatric in-patients receive a combination of potentially interacting drugs. As the severity and the clinical relevance of the different interactions are under discussion, clear arrangements about the medication surveillance system and the function of an automated interaction detection system, are needed.

BIPOLAR DEPRESSION: DIAGNOSIS AND TREATMENT Souery D. Erasme Hospital, Dept. of Psychiatry, Université Libre de Bruxelles, Brussels, Belgium Bipolar disorder (BPAD) is a long term illness requiring changes of treatment approaches at different phases and according to clinical manifestations. BPAD is associated with a significant degree of morbidity, particularly because such patients spend more time ill, have fewer periods of complete remission than patients with other affective disorders. Thus, the primary goals of treatment of BPAD are to treat both acute phases of the illness as well as to prevent recurrence. Treatment may be required for acute mania, acute depression, or to prevent recurrence of such states.

There is emerging consensus that the greatest unmet need in BPAD is the management of depressive episodes associated with the disorder. This observation is supported by the virtual absence in Europe of drugs that have received regulatory approval for use in bipolar depression and the lack of predictors of treatment response. Differences between BPAD and Unipolar Depression have been studied for years with controversial results. BPAD is often misdiagnosed as Unipolar Depression when exploration of symptoms is not adequate enough.

There exists an urgent need to identify clinical, genetic and psychosocial markers of treatment response in bipolar depression. New developments will be reviewed and discussed in light of their clinical usefulness. plicate therapeutic decisions. Within the last years, psychotherapeutic interventions including psychoeducation gained evidence and therefore, attention. The treatment course overall is mostly complex with the need of frequent changes. Evidence-based guidelines might help to reach decisions at difficult points. In the talk an overview of current treatment strategies for the different phases and types of bipolar disorders will be given. Situations were further research is needed will be discussed.

CHILD AND ADOLESCENT BIPOLAR DISORDER Massat I. Laboratoire de Neurologie Expérimentale, Erasme, Brussels, Belgium Many advances in the knowledge of the pre-pubertal and early adolescent bipolar disorder (PEABP) have been seen over the last 15 years. There is ongoing controversy over the validity and prevalence of PEABP. Confusion has resulted from attempts to apply adultderived diagnostic criteria to children without allowance for developmental differences and from use of excessively inclusive signs. However, there is a growing consensus that this disorder may not be rare, when considering its atypical presentation, as a varying developmental expression of bipolar disorder. Compared to adult population, PEABP is characterized by co-occurring symptoms of major depression and mania, a more chronic course, a poor response to mood stabilizers, and a high level of comorbidity, particularly with attention-deficit/hyperactivity disorder (ADHD).

The PEABP is also difficult to diagnose because of its symptomatic overlap with ADHD. This symptom overlap (which includes overactivity, irritability, distractibility, emotional lability, impulsivity and fast speech) causes much diagnostic confusion, despite the different ages of onset, and raises the fundamental question of the relationship between these disorders.

Current efforts focus on investigating clinical features developing more instruments for early diagnosis and improving treatment research. Longitudinal studies show that the course of illness tends to worsen with time but that early intervention could improve long-term outcome.

The scientific community promotes debates in order to evaluate which kind of treatment should be prioritized. The current consensus is that once the diagnosis has been determined, the pharmacological treatment should be immediately prescribed. However, the duration and the impact of early treatment on the course of the illness are not really known. Controlled studies involving this young population lack and many questions concerning PEABP treatment remain unanswered. Neurological soft signs (NSS) are frequent in patients with schizophrenia and their biological relatives. Neurological impairments (sensory dysfunctions, gait and balance impairment, dyscoordination, etc.) seem to be associated with the genetic risk for schizophrenia, even when the disease itself is absent. Their presence might be a valuable composite intermediate phenotype for genetic studies (Gourion et al, 2003) . Cohort studies in general population showed that presence of NSS increase the risk for an individual to later present schizophrenia (Leask et al, 2002) . Literature about ''At Risk Mental States'' for psychosis lacks for studies evaluating the possibility of such subtle anomalies to predict risk for transition to psychosis. In order to address this question, we have started a longitudinal prospective study in at risk mental states. Preliminary analyses were conducted in order to examine whether hypothesis NSS are associated with more cognitive impairment and neurodevelopmental anomalies. 60 young adults presenting ''at risk mental states'' have been included for a year in our program.

They were evaluated with CAARMS (Comprehensive Assessment of At Risk Mental State; Young et al, 2006 ) and a standardised neurocognitive evaluation was realised. NSS have been assessed in 19 subjects with a standardized examination (Krebs, 2000) . We will present our results on correlations between NSS, neurocognitive impairment and prodromal symptomatology explored by the CAARMS and discuss the interest of neurodevelopmental anomalies for closing in subjects with at risk mental states for psychosis.

Cognitive impairment is now considered as a core feature of schizophrenia. Cognitive difficulties are present in a large majority of patients, both at disease onset (Saykin et coll., 1994) and after the first years of treatment (Harvey et coll., 1999) . How cognitive difficulties evolve across the entire lifespan in patients with schizophrenia has been less thoroughly studied and results are still debated (Kurtz, 2005) . A first view, based on observations of patients experiencing a severe worsening in cognitive abilities with aging, especially after 65, consider schizophrenia as a ''neurodegenerative disorder'' (Harvey et coll., 1999; Friedman et coll., 2001) . Alternatively, others describe a relative consistency of cognitive performances across age, when compared to healthy controls (Zorilla et coll., 2000; Heaton et coll., 2001) . According to the latter view, schizophrenia is considered as a ''static encephalopathy' '. The aim of the present study was to use a comprehensive neuropsychological battery to evaluate whether cognitive deficits that are observed early in schizophrenia further decline when patients get older. In order to do so, we examined the interaction between aging and neuropsychological abilities in a cross-sectional study carried-out in 83 patients with schizophrenia and 65 healthy controls. Subjects were divided in 3 separate age groups: young (20-40), middle-aged (50-65) and old (>65).

Nineteen patients were not able to perform the entire neuropsychological battery. These patients were mostly over 65 and displayed severe deficits on basic neuropsychological screening tasks. In the remaining 64 patients, we also observed a general cognitive deficit.

However, an interaction with age was observed only in some cognitive tasks mostly involving executive functions.

The present results are consistent with a previous cross-sectional study carried out by Fucetola et coll. (2000) showing a disproportionate decline in some executive functions with aging in patients with schizophrenia.

SCHIZOPHRENIA: NEURODEVELOPMENTAL OR NEURODEGENERATIVE DISORDER Constant E.L. Cliniques Universitaires Saint-Luc, U.C.L., Brussels, Belgium Until the 1980s, schizophrenia was seen as a disorder of early adult onset and progressive deterioration. After the 1980s, schizophrenia began to be viewed within a neuro-developmental model. According to this model, schizophrenia would be the long term consequence of early abnormalities in neural development. According to neurohistological studies, in some brain areas, the neurons of schizophrenic patients fail to migrate normally to the outer layers of cortex, preventing the optimal establishment of neural connections.

Migration might be disrupted by processes that are under genetic control, or alternatively, by the presence of a nongenetic event such as a virus. Several neurohistological studies have been conducted using the brains of schizophrenic patients obtained upon autopsy. There appears to be too few cells in the superficial layers of the cortex and too many cells in the deeper layers. This suggests, in deed, that the neurons failed to migrate as far as they should have. This displacement prevents the optimal establishment of neural connections. But why do the symptoms begin so much later than the underlying neural events? We have evidence of cellular disruption in the prefrontal cortex of schizophrenic patients. This area is not fully myelinated and therefore not fully mature until late adolescence. Perhaps a disruption in cell migration occurs in the second trimester, but the effects of this problem are not completely appreciated until the prefrontal cortex is called on to perform cognitive operations some two decades later. On the other hand, following Kraepelin (1871) , the key pathophysiology of schizophrenia is neurodegeneration. Patients with schizophrenia experience clinical deterioration that leads to occupational and social dysfunction. Recent brain imaging data suggest that early progressive brain volume changes in the first year after the diagnosis of schizophrenia predict the 5-year outcome of schizophrenia. The patients who had the largest decrease in grey matter in the first year had the highest negative symptom scores and were less likely to live independently 5 years after this first evaluation. Neurodevelopmental abnormalities and later neurodegeneration are not exclusive processes. In fact, both may predominate at different illness stages and in different subtypes of that condition.

PRODROMAL SCHIZOPHRENIA Klosterkötter J., Schultze-Lutter F., Ruhrmann S. University of Cologne, Dept. of Psychiatry and Psychotherapy, Cologne, Germany While, in schizophrenia, the observation of a frequently extended prodromal period in the majority of first-episode cases even proceeded Kraepelin's and Bleuler's descriptions of the disorder, research on an early detection and treatment of the illness in its prodromal phase was rarely approached before the 1990s. Based mainly on the description of prodromal symptoms of schizophrenia in DSM-III and its revision as well as on findings of 'high risk' research, the 'ultra-high risk' (UHR) criteria were suggested in 1998 as the first definition of an imminent risk of frank psychosis predicting conversion within 12 months. They consist of attenuated psychotic symptoms (APS) in terms of five DSM-IV criteria of schizotypal personality disorder, of brief limited intermittent psychotic symptoms and the combination of a risk factor for psychosis, i.e. a schizotypal personality disorder or a positive family history for psychosis, and a recent, yet persisting significant decline in functioning. Besides an average 12-months conversion rate of 38% in UHR-subjects mainly at risk by APS and not receiving special anti-psychotic treatment, studies of UHR-samples have reported various impairments and aberrations for this clinical group incl. high frequency of 'co'-morbid psychiatric conditions, neurocognitive deficits and structural brain aberrations, such as an increase in gyrification. Based on the German psychopathological tradition, i.e. the basic symptom concept, in 2001, a complimentary approach to an even earlier was proposed defined by subtle, subclinical, selfexperienced disturbances of thought processes and perception. At a 20%-conversion rate in persons reporting these symptoms, the overall conversion rate to schizophrenia in a first prospective study with a nearly 10-years mean follow-up period was as high as 65%.

Furthermore, help-seeking individuals with predictive cognitive-perceptive basic symptoms also showed a high level of psychiatric 'co'-morbidity and -though less than UHR-subjectsneurocognitive deficits. In all, the results indicate that help-seeking individuals considered clinically prodromal for psychosis according to current prodromal criteria are ill and clearly qualify for psychiatric and/or psychological treatment. Yet, more research on larger samples and with longer follow-ups is required to further improve prognostic accuracy of criteria and to possibly distinguish prodromes of other psychotic disorders from prodromal schizophrenia. The aim of the session is to analyse if an early diagnosis of dementia has real implications on the medical strategy and management and if this really influences the disease course. When a patient comes to us presenting signs and symptoms of an early dementia we all try hard to make a proper and detailed differential diagnosis.

Two problems arise constantly. The first one is the challenge: how far can we actually go into that? The second one is the even more important challenge: are there really therapeutic consequences? The answers can be yes, no or somewhat in between.

The symposium will develop these visions and their practical consequences. Patient characteristics (e.g. age and co-morbidity), the evolution of the disease (e.g. aggressive course and caregiver distress), behavioural and psychological symptoms (e.g. hallucinations and agitation) may play a role in the final therapeutic options. Behavioural observation is an important clinical tool for early diagnosis of frontotemporal dementia (S. Engelborghs). The early presentation of Alzheimer's disease includes some specific characteristics one must draw attention to (S. Bakchine). Uncommon degenerative dementias call for early diagnostic recognition and adjusted management issues (A. Kurz) .

State-of-the-art propositions will be presented as well on the non medical management of the patient with dementia (e.g. family support and reality orientation therapy) as on medication (e.g. acetylcholinesterase inhibitors, SSRI's and neuroleptics). A complementary problem will also be considered. Are there sound arguments that we will prefer one AChEI rather than another in accordance with the differential diagnosis we made?

The speakers of this session discuss their results in a life-span perspective. Their research is important for every-day biopsychiatric practice. With the development of new treatments for Alzheimer's disease (AD) that may not to be efficacious in the treatment of frontotemporal dementia (FTD), there is an increasing need for distinguishing FTD from AD. Moreover, a different prognostic profile of FTD versus AD strengthens the need for (early) differential diagnosis. Despite striking neuropsychological and behavioural differences between FTD and AD, clinical diagnostic criteria often fail to differentiate FTD from AD. Although a combination of behavioural, neuropsychological and physical findings was useful in distinguishing FTD from AD, behavioural quantification appeared to be more sensitive than cognitive testing in FTD. However, frequently used behavioural assessment scales lack sensitivity for FTD as they have specifically been developed for AD. Therefore, behavioural assessment scales that are based on systematic behavioural observation of frontal lobe symptoms might be helpful tools for diagnosing FTD. We therefore developed the Middelheim Frontality Score (MFS), a disease-long clinical and behavioural assessment tool that measures frontal lobe features. The MFS consists of ten items that are scored either zero (absent) or one (present) yielding a total maximal score of 10. In order to assess discriminatory power and intra-and interrater variability, a prospective study was set up, including patients with probable AD (n=400) and FTD (n=62). Applying a total MFS score of 5 as cut-off for discriminating FTD from AD, specificity and sensitivity values of 89% were achieved. Intra-and inter-rater variability was calculated in different study populations by means of retest correlation, revealing moderate to strong positive correlations of high statistical significance. We hypothesise that the discriminatory power of behavioural observation will even be higher in the earliest disease stages given the relatively low mean MMSE scores of AD patients (13. 9±6.9 ) that were included in the latter study.

Indeed, new and unpublished data dealing with patterns of onset of frontal lobe symptoms in relation to dementia severity, show that the MFS total score increases when AD progresses (as measured by the global deterioration scale) whereas FTD patients tend to show more stable MFS total scores with disease progression.

UNCOMMON DEGENERATIVE DEMENTIA: DIAGNOSTIC AND MANAGEMENT ISSUES Kurz A. Dept. of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Sporadic Alzheimer's disease (SAD) accounts for more than 60 per cent of all dementias.

There are several less common neurodegenerative causes of dementia which nonetheless require attention, because they are associated with special patient and caregiver problems, treatment decisions, and prognostic considerations. (1) Familial Alzheimer disease (FAD) is caused by mutations in genes located on chromosomes 1, 14, and 21. FAD has an onset before the age of 60 years and is associated with a particularly rapid cognitive decline.

Cholinesterase inhibitors may be used to slow the progression of symptoms, but there are no specific drug trials in FAD. Patients and family members require psychological and genetic counseling. (2) Posterior cortical atrophy (PCA), also termed progressive posterior cortical dysfunction, is characterised by neuropsychological dysfunction attributable to the parietal and occipital association cortices including visual agnosia, optic ataxia, and dressing apraxia. Since PCA often is an atypical variant of SAD a cholinesterase inhibitor may be tried. In addition, occupational, physical, and speech therapy may help in managing disability. (3) Frontotemporal lobar degenerations can present as frontotemporal dementia, semantic dementia, or progressive aphasia (PA) according to brain localisation. These clinical variants are associated with prominent personality change, loss of semantic knowledge, and non-fluent language disorder, respectively. Since cholinesterase inhibitors are ineffective, pharmacological treatment focuses on selective serotonergic antidepressants to alleviate apathy, compulsive behaviour, abnormal eating behaviours, disinhibition and irritability.

Trazodone has been successfully tried to improve aggressiveness and agitation. Non-pharmacological strategies include daytime structuring, token rewards, and implementing daily routines. In PA, speech therapy may be tried. Counseling and support of caregivers is as important as in Alzheimer's disease. (3) Dementia with Lewy bodies (DLB) differs from Alzheimer's disease (AD) in terms of marked fluctuation of symptoms, vivid visual hallucinations, intolerance of antipsychotics, and Parkinsonian symptoms. Cholinesterase inhibitors are probably as effective as in SAD. For the treatment of psychotic symptoms atypical antipsychotics should be used with caution. Management must take into account attentional problems and movement disorder. Dementia in Parkinson's disease is clinically similar to DLB, but motor symptoms are more prominent and precede cognitive decline by several years. There is marked slowness of information processing. The movement disorder is treated by medications that enhance dopaminergic neuro-transmission. Cognitive impairment may respond better to cholinesterase inhibitors than in SAD. (4) Clinical features of progressive supranuclear palsy include lack of coordination, stiffness of neck and trunk, difficulty with voluntary eye movements, motor slowing, proneness to falls, and subcortical dementia. Response to dopaminergic agonists is usually poor. Non-pharmacological management should include physiotherapy. (5) Corticobasal degeneration is characterised by poor coordination, akinesia, rigidity, myoclonus, postural instability, limb dystonia, and cognitive impairment. Dopaminergic drugs are rarely beneficial. Tremor and myoclonus may be controlled with clonazepam. Rigidity may respond to baclofen. (6) Amyotrophic lateral sclerosis (ALS) affects both upper and lower motor neurons throughout the brain and spinal cord. Symptoms include muscular weakness, atrophy, fasciculations, cramps, dysarthria, and dysphagia. ALS can be associated with a frontal lobe dementia. Riluzole prolongs survival by 3 to 6 months. Treatment should include occupational therapy, physiotherapy, and speech therapy. (7) Huntington's disease is a genetic disorder caused by excess trinucleotid repeats on chromosome 5. Essential features are hyperkinetic movement disorder (chorea), postural instability, Parkinsonism, dystonia, personality change, and subcortical dementia. Chorea may respond to dopamine antagonists, and physiotherapy is essential. The identification of clinical and neurobiological correlates of suicidal behaviour has led to the formulation of an explanatory stressdiathesis model. This model incorporates clinical characteristics such as impulsive aggression, mental pain and hopelessness, and biological characteristics relating to disorders of the serotonergic and noradrenergic neurotransmission systems and the hypothalamic-pituitary-adrenal axis. Moreover, the association between these biological and clinical characteristics is becoming clear. Neuropsychological processes involving attention, memory, emotion recognition and decision making may be crucial for our understanding of this relationship. Genetic epidemiology provides support for the findings from earlier studies suggesting a genetic predisposition to suicide studies by showing that interplay between genetic and environmental influences may lead to the development of the predisposition to suicidal behaviour. A number of candidate genes have been identified. In addition, the study of gene expression in brain regions of interest and the study of the effects of gene polymorphisms on brain structures yield interesting results. While these findings increase our insight in the neurobiological mechanisms underlying suicidal behaviour, for the clinician there is emerging evidence that biological testing can supplement clinical judgment in predicting the risk of suicidal behaviour. There are opportunities for new therapeutic targets aiming at the prevention of the development of the diathesis or of its fatal consequence, i.e. suicide.

NEUROMODULATION USING DEEP BRAIN STIMULATION IN PSYCHIATRIC DISORDERS Sturm V. Dept. of Stereotactic and functional Neurosurgery, University of Cologne, Germany Permanent high frequency-DBS has been proven highly effective in the treatment of Parkinson's Disease and other motor disorders. The minimally invasive nature along with the full reversibility of the stimulation-effects permitted the application of DBS in clinical studies on severe psychiatric disorders, resistant to conventional (pharmacological psycho-therapeutic, electroconvulsive) treatment.

Clinical trials have been performed in obsessive-compulsive disorders, Tourette's symptoms and major depression during the past 6 years. Favoured target areas have been the anterior limb of the internal capsule (treatment of OCD), the internal segments of the globus pallidus or the centrum medianium-parafascicularis complex of the thalamus (treatment of Tourette's syndrome) the subgenual cingular cortex of Brodmann-area 25 (treatment of major depression and, introduced by our group, the nucleus accumbens for treatment of both OCD and major depression.

The latter nucleus has a prominent function in amygdalo-basal ganglial-prefrontal circuitry as well as in the mesolimbic dopaminergic reward-system.

Thus, DBS in the nucleus accumbens is effective in the treatment of OCD (amygdalo-prefrontal circuit) Tourette's syndrome (amygdalo-basal ganglia-prefrontal circuit) and major depression (dopaminergic reward system). The results of ongoing studies are presented.

Although effective and fully reversible, the standard DBS procedure (permanent high frequency-stimulation) has the drawbacks of interfering with the physiological activity of the stimulated structures and of not being able to reorganize disturbed synaptic activity within the respective neuronal networks.

Together with the Research-Center Jülich (Prof. Tass) we are developing new, specifically desynchronizing stimulation algorithms which do not interfere with the physiological activity of the stimulated structures and may have the potential to restore disturbed synaptic function permanently. Background: Deep Brain Stimulation (DBS) is a neuromodulation technique that involves the implantation of electrodes into specific parts of the brain. DBS is reversible, nondestructive, and can be modified by adjustment of the stimulator settings after implantation. Despite advances in biological treatment and psychotherapy for obsessive-compulsive disorder (OCD) as well as for major depressive disorder (MDD), a substantial number of patients fail to improve.

Since 1998 we investigate DBS as a therapeutic option for severe, treatment-refractory obsessive-compulsive disorder (OCD). DBS in the ventral part of the anterior limbs of the internal capsules induced clinically significant therapeutic benefit in OCD, not only in severity of OCD symptoms, but also on the mood scores. Based on the results of DBS in OCD, we initiated in 2004 a study to investigate the effectiveness, safety, and tolerability of DBS in the same target for treatment-refractory MDD.

Methods: Patients with severe, longstanding, treatment refractory OCD (n=16) and patients with a longstanding history of MDD (n=3) were carefully selected. They failed to improve after years of adequate trials of pharmacotherapy, psychotherapy, electroconvulsive therapy and even experimental interventions. Quadripolar electrodes were implanted bilaterally in the ventral part of the anterior limb of the internal capsule. The patients were assessed with a standardized and detailed psychiatric assessment on a regularly scheduled basis, both at baseline (within a month prior to implantation) and postsurgically. Symptom severity was measured with the Yale-Brown obsessive-compulsive Scale (Y-BOCS) for OCD, with the Montgomery-Asberg Depression Rating Scale (MADRS) for MDD.

Results: With long-term chronic DBS (follow-up time between 111 and 6 months), 12 out of 16 OCD patients showed a clinically significant reduction in symptom severity, with a decrease in baseline YBOCS varying between 37 and 97%. After six months of chronic DBS, all 3 MDD patients showed a clinically significant reduction in symptom severity of 50 percent or greater on the MADRS. Two of the three MDD patients were in remission.

Conclusion: Further research is warranted, but patients with severe, longstanding, treatment-refractory OCD or MDD may benefit from DBS in the ventral part of the anterior limb of the internal capsule. Basal ganglia consist of central grey nuclei which process cortical information and send back an efferent message to the frontal cortex. The three cortical functional territories, motor, associative and limbic, process motor, cognitive and emotional information and transmit distinct output to separate regions of the basal ganglia. Many aspects of psychiatric disturbance have been linked to dysfunction of the basal ganglia, or their connections with other brain regions. Thus, in Tourette syndrome and obsessive-compulsive disorders (OCD), current pathophysiological models favour a dyfunction of the striato-pallido-thalamo-cortical circuit. In Parkinson's disease (PD), non-motor therapeutic effects of high frequency subthalamic nucleus stimulation, suggest that modulation of downstream associativo-limbic regions in the basal ganglia could improve behavioural disorders as it has been shown in Tourette syndrome. Given its organisation and its position, and in spite of its small size (10 · 6 · 3 mm), the subthalamic nucleus can receive and process information from diverse sources. Recently, we suggested that the three functional modalities (sensorimotor, cognitive and emotional) could be combined in the very small volume the subthalamic nucleus which thus would serve as a nexus for the integration of motor, cognitive and emotional components of behaviour (1) . The role of the subthalamic nucleus in the control of behaviour, the improvement of anxiety, repetitive behaviors, obsessive-compulsive symptoms, and OCD in PD patients treated by stimulation of the STN (2) (3) (4) , the long-term effects and safety of subthalamic nucleus stimulation in PD patients, and the possibility to focus high frequency stimulation to a small finely-defined structure using validated procedures led us to propose the subthalamic nucleus as a target for the treatment of highly-resistant OCD. Tardive dyskinesia (TD) is sometimes a highly disabling side effect of antipsychotic treatment for which medical treatment often gives disappointing results. There has been a renewed interest in surgical treatment for various movement disorders in recent years.

Continuous high frequency stimulation (HFS) of the globus pallidus has been shown to be effective in reducing or even stopping various types of hyperkinetic movements. We assessed the efficacy of bilateral HFS of the globus pallidus to treat severe TD in a prospective French multicentre study. Ten patients with severe TD refractory to medical treatment were included in the study and followed at least 6 months after surgery. TD severity was assessed by the extrapyramidal symptoms rating scale (ESRS) before, 3 and 6 months after surgery. Out of these patients, all had dystonia (sustained muscle contraction leading to abnormal posture) affecting limb or trunk, 7 had choreic-like movements and 6 presented oro-lingual masticatory dyskinesias. At 6 months after surgery, the ESRS score had decreased compared with baseline by more than 40% in all patients (mean improvement = 61%; range: 44-75%).

Compared to baseline, the ESRS dystonia score was decreased by 68% (28-89%) (p=0.006), and the ESRS choreic score by 53% (27-75%) (p=0.006). The improvement of oro-lingual masticatory dyskinesias was more variable: one patient was free of dyskinesias, 3 had moderate improvement (33 to 63%) and two had no clear beneficial effects. There were no marked changes in the patient's psychiatric status. Although these results need to be confirmed in a larger group of patients with a longer follow-up, bilateral globus pallidus stimulation seems to be a much-needed treatment option for patients suffering from disabling TD.

SCHIZOPHRENIA AND CHROMOSOMAL ABERRATIONS (22Q11 DELETION SYNDROME) Thibaut F., Raux G., Bumsel E., Hecketsweiler B., Frébourg T., Campion D. University Hospital Ch. Nicolle and Le Rouvray Hospital, Rouen, France Schizophrenia is a complex, multifactorial and polygenic disease. Linkage and association studies have identified candidate genes for schizophrenia. However, most of the alleles or haplotypes identified so far showed only a weak association. Microdeletion 22q11.2 (22q11DS) is the most frequent human chromosomal deletion (with an estimated prevalence of 1/2500-1/4000 live births). Velocardiofacial syndrome is attributed to this microdeletion.

DNA sequence variations within the 22q11 velo-cardio-facial syndrome chromosomal region are likely to confer susceptibility to psychotic disorders. Indeed, there is an increased prevalence (25-30%) of schizophrenia among patients with the 22q11 deletion syndrome, comparable to the risk to offspring of two parents with schizophrenia. This region has also been implicated in schizophrenia by previous linkage studies. The PRODH gene, which encoded the mitochondrial enzyme proline dehydrogenase, is located in this region.

Homozygous deletion and/or missense mutations of this gene were associated with high plasma proline levels, severe mental retardation and epilepsy. The same molecular alterations, but at the heterozygous state, were associated with moderate hyperprolinemia in certain forms of psychosis. The COMT gene, located in this region, which is involved in the breakdown of dopamine is also a candidate gene for schizophrenia. The combination of bearing the Met allele on the remaining allele of the COMT gene and hyperprolinemia constitutes a risk factor for psychosis in 22q11 deletion patients.

features of the 22q11 deletion syndrome. G Our research group has focused on the reduction of processing speed in schizophrenia, and its contribution to a cluster of symptoms defined as psychomotor slowing. In the first part of this lecture an overview will be given on psychomotor symptoms in schizophrenia. Four groups of symptoms have been described, some of them in the nineteenth and early twentieth century, e.g. by Kraepelin and Bleuler: (1) catatonic symptoms, (2) psychomotor slowing, (3) neurological soft signs (NSS), (4) and extrapiramidal dysfunctions. We will focus on the symptomatology and course; the interrelationships; the relationships with positive, negative, cognitive, and depressive symptoms; the assessment; the neurobiology; and treatment options.In a second part research data of our group will be presented on psychomotor slowing, as measured by the Symbol Digit Substitution Test, and by computerized analysis of performances during copying tasks. It will be argued that in psychomotor slowing a distinction has to be made between sensorimotor and cognitive slowing, that these processes are unrelated and are differentially influenced by antipsychotic medication. Thirdly the symptom of stereotypy will be observed, using a newly designed computerized Stereotypy Test Apparatus (STA). Differences are described between stereotypy and perseveration during the course of the illness. Differential effects are found on STA performances between atypical antipsychotics and conventional neuroleptics. Finally it is proposed that the domain ''Processing Speed'' in the MATRICS-initiative has to be delineated from psychomotor slowing in order to properly assess cognitive functioning in schizophrenia. Furthermore, psychomotor slowing and stereotypy seem to have different characteristics than the established cognitive deficits in schizophrenia: they seem to be associated with positive symptoms, they tend to increase in later stages of the illness, and are unaffected or even tend to worsen by treatment with conventional neuroleptics.

NEUROIMAGING AND SCHIZOPHRENIA Gruber O. Dept. of Psychiatry and Psychotherapy, Georg August University, Goettingen, Germany Modern neuroimaging techniques make it possible to determine brain structural and functional characteristics in schizophrenia and other psychiatric disorders. In part, these characteristics may serve as intermediate phenotypes, i.e. biological markers, which may help to clarify genetic and other pathophysiological factors that are involved in the pathogenesis of psychoses. In this talk, recent findings from studies using structural and functional MRI will be presented. First, the potential neuregulin-1 risk haplotype HAP ICE appears to be associated with low hippocampal volume and, in this way, may contribute to the vulnerability for schizophrenia and other psychotic disorders. Second, genetic polymorphisms of serotonergic and dopaminergic neurotransmission seem to differentially affect neurofunctional subsystems of working memory, which are considered to represent promising endophenotypes both in schizophrenia and in bipolar affective disorder. Third, both neurocognitive and neuro-physiological parameters acquired during specific testing of working memory performance may provide important information for differential diagnosis between different types of psychoses. Finally, there is evidence that brain imaging may also help to predict clinical outcome, treatment response and the potential for relapse after treatment. In conclusion, neuroimaging contributes to a better understanding of the pathophysiology of schizophrenia and other psychotic disorders, and may allow more individual and effective treatment planning in the future. Pharmacotherapy is the keystone of treatment for mental conditions such as schizophrenia, bipolar disorder and major depression. Prediction of both efficiency and adverse drug effects of antipsychotic and antidepressants would help to reduce prolonged hospitalization and therapeutic failures, and improve compliance and long term prognosis of those severe and frequent disorders. Pharmacogenetic studies are ongoing since twenty years, trying to improve this prediction. They mainly focused on clinical improvement for antidepressant response. For antipsychotics, side-effects as tardive dyskinesia and weight gain and clinical improvement have been assessed in pharmacogenetic studies. Current knowledge on genetic prediction of general response and drug-induced side effects will be reviewed and then the key issues that need to be taken into consideration in designing and interpreting pharmacogenetic studies of psychotropic drugs will be discussed.

PHARMACOGENOMICS AND PSYCHOTROPIC DRUG USE IN CHILDREN AND THE ELDERLY Vandel P., Haffen H., Sechter D. Service de Psychiatrie de l'Adulte, Centre Hospitalier Universitaire, Besançon, France Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. For many drugs, pharmacogenetic polymorphisms are known affecting biotransformation and clinical outcome. The clinical importance of these variants depends on allele-frequency and the effect size of the clinical outcome parameters.

Psychotropic drugs prescription treatment becomes more complicated concerning children, adolescents, and elderly patients. These risks are associated with age-related physiological changes and individual variability in drug metabolism related to several factors. In children the processes that govern drug metabolism, the underlying pharmacogenetic determinants that may control either the affinity or the capacity of a drug or toxicant substrate for the enzymes responsible for its biotransformation appear to be altered as a function of development.

Pharmacokinetic consequences are important to know in order to prevent psychotropics over-or underdosing. In the elderly and as patients age, psychotropic use and pharmacological treatment becomes more complicated due to an increased risk of adverse drug events. These risks are associated with age-related physiological changes and individual variability in drug metabolism related to several factors, the most frequent of which is polymedication as a result of coexisting chronic illnesses. Comedications induce drug interactions that depend on the patient's metabolic capacity linked to the genetically determined cytochrome P450 enzyme (CYP450) function. In the elderly the most frequent is polymedication as a result of coexisting chronic illnesses. The potential use of pharmacogenetics in children and elderly psychopharmacology will be discussed. To give an overview of the special situation of child and adolescent psychopharmacology in Europe. Modern psychopharmacology started with the use of stimulants for treating children with disruptive behaviors in the 30 th of the last century. All further development like the introduction of neuroleptics or antidepressants had been based on experiences in adult patients and often data on children and adolescents are lacking. At the moment, we still have a high proportion of so called off label use (using medication approved for adults but non approved in that age group) in child and adolescent psychiatry in Europe. Based on international comparisons for the main substance classes marked differences in prescription rates between the US and Europe will be demonstrated. Local trends like prescription of herbal compounds in Germany will be described (Fegert et al., 2006) . The new EU regulation (Kölch et al., 2007) will increase the number of GCP conform studies in psychopharmacological medication in children. Anyhow some IRFs very important to everyday practice like the combination of psychosocial interventions and medication are only studied in publicly founded NIMH sponsored trials like the MTA study, TADS etc. (Vitiello et al., 2004) . Our increasing knowledge on developmental neurogenesis in the brain and pharmacokinetic and pharmacodynamic differences from adults should lead us to a more careful evaluation of psychotropic medications in children. The debate on potential harm of SSRIs, suicidality and related warnings of the FDA and European regulatory agencies makes clear that we need more age specific data on new medications and a well organized post marketing surveillance for all psychotropic substances used in children and adolescents. A therapeutic drug monitoring multicenter network including serum level measurements as well as standardized documentation of drug efficacy and drug safety could be one of the first solutions to that problem (Gerlach et al., 2007) . EEG mapping studies in untreated depressed patients as compared with normal controls demonstrated a decrease in absolute power in all frequency bands, an augmentation of relative delta/theta and beta and a decrease in alpha activity as well as a slowing of the delta/ theta centroid and an acceleration of the alpha and beta centroid, reflecting a decrease in vigilance.

In the alpha asymmetry index, depressed patients showed right frontal hyper-and left frontal hypoactivation. Low-resolution brain electromagnetic tomography (LORETA) identified cerebral generators responsible for these differences. Regarding antidepressants, at least 2 types of pharmaco-EEG profiles were seen: a thymoleptic type with sedative effects and a thymeretic one with activating properties. In event-related potential (ERP)-LORETA, depressed patients showed reduced P300 source strength bilaterally temporally and medially prefrontally, reaching to rostral parts of the anterior cingulate. Contrarily, citalopram increased P300 source strength in the left prefrontal cortex and precuneus, reaching to the posterior cingulate. Similarly, ademetionine increased LORETA power also in dorsal frontal regions and the posterior cingulate cortex and decreased it in ventral limbic regions. These reciprocal limbic-cortical changes are similar to PET data after fluoxetine and opposite to alterations in depression. These findings will be discussed in the light of a key-lock principle regarding diagnosis and treatment of depression.

NEUROBIOLOGY OF ALCOHOLISM Lentner S. Anton-Proksch-Institute, Vienna, Austria Alcohol is probably the most widely used drug in the world, and almost no other substance has been as comprehensively studied as alcohol. In addition, alcohol demonstrates a unique and interesting pharmacology.

Current research has identified a variety of neurobiological factors that are involved in the pathogenesis and maintenance of alcoholism.

Unlike previously assumed, predisposing factors do not include moral factors such as debauchery or lack of a strong will. Instead, the disposition to alcoholism seems to be associated with the rather unsuspicious ability to consume high amounts of alcohol without experiencing unpleasant effects. The knowledge about the neurobiological basis of alcoholism is increasing and may lead to the use of specific medications in treatment program. At the beginning, PTSD research was primarily focused on war veterans and victims of bodily assault or rape. Starting in the early 90s, PTSD after civilian traumas such as motor vehicle accidents was diagnosed increasingly more often. Recent publications showed that PTSD can also follow serious somatic diseases. A Survey is given on published studies exploring the incidence of posttraumatic disorders after severe medical states and associated treatment modalities. Awareness during anaesthesia, prolonged ICU treatment (ARDS, septic shock), burns, and successful resuscitation after cardiac arrest, coronary artery bypass surgery, organ transplantation and cancer were all linked to the development of PTSD. Prevalence of PTSD in these medical conditions lies around 5-10%, and it is therefore considered an important comorbidity. Unfortunately, diagnosis and treatment of PTSD are not well enough established yet and thus do receive too little attention in the treatment regime of somatic illness.

Generally, PTSD can occur with every life-threatening disease, but possibly also with less severe diseases, if the patient experiences intense fear. PTSD symptoms, especially intrusive recollections, avoidance and hyperarousal can impair the patients' quality of life more then the primary disease. This seems to be also true for subsyndromal PTSD. To adequately diagnose and treat patients at risk of developing PTSD, close collaboration between physicians and psychiatrists will be necessary. For more than 30 years researchers sought to find the insight into the brain via different ways.

Whereas in the older times neuroendocrinological methods were used either in a circadian fashion or with challenge methods, subsequently tryptophan depletion was used to uncover the underlying monoaminergic function of neuroendocrine as well as biochemical measurements. Lately brain imaging techniques using different radio ligands have been used successfully and replaced simple blood-flow measurements which could not yield a difference between different diseases. Although interesting findings have been obtained in depression, anxiety disorders as well as in schizophrenia and dementia, there is still a lack of data to identify characteristic and discriminative characteristics between these disorders. This is partly due to the nature of the studies since each receptor system necessitates individual measurements. The serotonin transporter has been studied most intensively and lower values have been obtained in depressed patients in hypothalamic regions. For example, anxiety disorders have been studied with respect to the 5HT1A receptor and again a lower activity has been found in these disorders. Interestingly higher 5HT1A receptor findings have been obtained in schizophrenia in specific limbic areas. Future aspects of neuroimaging monoaminergic function include not only a standardised methodology with regard to the timing of the measurements in the circadian rhythm but also taking into account the seasonal variations as well as the menstrual cycle. Furthermore, the combination with genetic data seems to be important because monoaminergic function has been shown to be under control of genetic influences, e.g. the serotonin transporter polymorphism. Neuroimaging of monoaminergic function is right now a research tool but hopefully will be available in the future also for diagnostic and specifically therapeutic purposes to find the right type of therapy. Ethical implications of ECT in adolescents are analyzed in the light of general medical ethics, which include five prominent principles: respect for autonomy, beneficence, non-nuisance, justice, and cautiousness. As adults, adolescents with acute psychotic impairment raise an inherent conflict between the respect for the patient's autonomy on one side, and the principle of beneficence on the other. However, this age group presents particular dilemmas: (i) As any adolescent suffering from a psychiatric illness is a highly vulnerable subject, society asks for particular attention. The consequence of potential overprotection is that the adolescent may remain untreated because of unrealistic fears regarding ECT. (ii) Some of these fears are linked to the cognitive secondary effects of ECT. Although preliminary data are reassuring, more empirical research on this population should be encouraged as only one follow-up study is available. (iii) Cautiousness recommends the use of ECT in limited indications: catatonia, mood disorders, and intractable acute psychotic disorders. In these indications, efficacy is reached in 80% (50 to 100 %) of the cases according to 9 recent studies that included 211 adolescent ECT treatments. This debate should also include patients' and families' experiences and views on ECT. Two independent groups recently showed that most adolescents patients who were given ECT, and their parents, had overall positive views on the treatment. They both considered ECT as a helpful treatment. Despite some frequent memory impairment, many of them will accept this therapy again if necessary.

Conclusion: We conclude that ethical options in clinical practice must be evaluated empirically with respect for the consequences on the patient. There is no ethical reason to ban the use of ECT in adolescents. Dogmatic views should be set aside. Epidemiological data show that the prevalence of depression in old age is high, is often underdiagnosed and undertreated, has a high rate of recurrence and is associated with significantly increased mortality. Because the prevalence of suicidal ideation is also relatively high in the old age, effective suicide prevention is especially needed for this age group. In addition, older patients experience more and longer major depressive episodes together with increased general medical comorbidities. Considerable comorbidity exists with dementia, stroke and Parkinson's disease, where patients often suffer from depressive symptoms. The response to antidepressant treatment in the elderly apparently does not differ from treatment response in younger patients. However, relapse rates are higher, and the longitudinal outcome is less favorable than for middle age. The more adverse longitudinal course in old age may more plausibly be explained by medical comorbidity, immobility and psychosocial factors than by age itself. It is also generally accepted that elderly depressed patients are particularly prone to the side effects of antidepressants, particularly cardiovascular side effects and treatment-related cognitive dysfunction. ECT has been shown excellent clinical effectiveness in geriatric patients. Despite specific side effects such as greater cognitive impairment, efficacy is greater in older than in younger patients. Recent improvements in the use of ECT include methods to maintain good therapeutic efficacy together with better tolerability concerning cognitive disturbances. Modified ECT techniques, including unilateral and bifrontal brief pulse wave stimulation and anesthesia with muscle relaxation substantially further enhance safety and tolerability. A reduced mortality in comparison to other treatments has been shown. Therefore to date on the long term no absolute medical contrain-dications to the use of modified ECT in geriatric patients, particularly in patients at specific medical risks, are encouraged. All potential benefits and risks have to be estimated on an individual basis. In the case of specific risks, interdisciplinary counseling may be necessary. Potentially higher somatic risks must be compared with the risk of insufficiently treated or prolonged psychiatric illness to optimize treatments especially in the old age. The chart analysis of more than 5000 electroconvulsive treatments confirms a good efficacy and tolerability especially in the group of older patients. Significant shorter treatment intervals until sufficient treatment response and remission could be observed especially in the group of patients older than 60 years. Efficacy, tolerability and safety data will be presented and discussed. Electroconvulsive therapy (ECT) is a safe and effective treatment for severe mood and psychotic disorders. When discontinued, however, without post-ECT treatment high relapse rates are seen within the first 4 to 6 months (Sackeim et al., 2001) . Psychopharmacologic treatment after an ECT-course is recommended to decrease relapse rates. A number of patients, however, are refractory to psychopharmacologic treatment. In these cases, maintenance ECT can be of help. In recent randomised controlled trial, a fixed number of maintenance ECT sessions was as effective as the combination of lithium and nortriptyline (Kellner et al., 2006) . Unfortunately, other randomised trials are virtually lacking. These are urgently needed, so as to provide the necessary evidence for maintenance ECT to gain its proper position in 'evidence based' treatment guidelines. 

NEUROBIOLOGY OF CRAVING Heinz A. Klinik für Psychiatrie und Psychotherapie, Charité Universitätsmedizin, Campus Charité Mitte, Berlin, Germany

Alcohol-associated stimuli that are regularly associated with alcohol intake can become conditioned cues that elicit alcohol craving and motivate alcohol intake. We examined brain activation elicited by alcohol-associated and by neutral or emotionally positive and negative stimuli and assessed the correlation between cue-induced activation and the prospective relapse risk. We used fMRI and visual alcohol-associated and control cues in 1) a block design and 2) a single-event design to assess brain activation in altogether 22 detoxified alcoholics and control subjects. Furthermore, we examined dopamine synthesis rate, D2 receptor availability and mu-opiate receptor availability in alcoholics. Patients were followed for three months and alcohol intake was recorded. In detoxified alcoholics, alcohol craving was associated with decreased dopamine synthesis rates and D2 receptor availability and increased mu-opiate receptor availability in the ventral and central striatum. In the fMRI study with a block design, alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Increased functional activation to alcohol cues in the medial prefrontal cortex correlated with decreased D2 receptor availability in the ventral striatum. A multiple regression analysis showed that in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cueinduced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning. In the single-event design, brain activation elicited by positive stimuli in the frontal cortex and ventral striatum of alcoholics was negatively correlated with the prospective relapse risk. These studies show that 1) alcohol craving is modulated by dopamine dysfunction and elevated mu-opiate receptors in the ventral striatum, 2) the degree of brain activation elicited by alcohol pictures presented in a block design in the anterior cingulate, medial prefrontal cortex and striatum was associated with the prospective relapse risk, and that 2) high brain activation elicited by emotionally positive cues was correlated with a low risk of relapse.

Patients may be at increased risk of relapse if they respond more strongly to alcohol-associated instead of emotionally positive stimuli. Gene-Environment interactions approach could explain some epidemiological and clinical factors associated to addictive behaviors. Twin studies first help to disentangle the respective role of environment and genetic effects, finding convincing evidence for common genetic vulnerability in several addictive behaviors. Assessing gene x environment interaction, need specifically designed studies, using multiplicative or additive approaches. Focusing on this GxE interaction already showed its relevancy in many recent studies, using both epidemiological and molecular approaches. For example, in a non-human primate model of alcohol dependence assessing the respective role of genetic vulnerability and severe fostering conditions, the only group that has a significant risk of using spontaneously alcohol is the group of monkeys that have both risk factors, i.e. being peer-raised and having the short allele of the gene coding for the serotonin transporter (Barr et al., 2005) .

Such approach was used to assess which factors are involved in the high mortality rate of alcohol-dependence. We analysed the survival status of a male alcohol-dependent sample (n=126) recruited 9 years before, and compared the 61 surviving patients to the 41 patients who died during this period (representing 81% of the initial sample). We found that the C allele of the 5-HT 1b gene, and tobacco dependence, were more frequently observed in the non-surviving patients.

In another study, we analysed the role of initial tolerance to alcohol, tobacco and cannabis in the risk of abuse and/or dependence in a sample of 3,000 student teenagers from one region in France. We focused on familial history for either of this drug of abuse, and found that indeed patients with a high genetic loading (G) had a higher initial tolerance to alcohol and cannabis during their first intoxications (E), and that this tolerance was a significant risk marker of alcohol and cannabis abuse or tolerance (G*E).

Gene-Environment interactions approach could help to select more accurately specific candidate genes, to identify more homogenous subgroups of patients (as sharing the same genetic vulnerability), to understand how genetic factors mediate the risk for associated psychiatric disorders, and ultimately, may lead to more focused, i.e. more efficient, prevention strategies. Within a neuro-cognitive framework addiction can be conceptualized as a dual-process pathology. On the one hand different neuro-cognitive functions and dimensions are being identified that are reflective of an increase in salience attribution regarding substance use and related cues. These cognitive dimensions include attention processes, which play an important role on an implicit, unconscious level. Changes in these cognitive processes develop in the course of addiction and drive cue-reactivity, craving and ultimately relapse. On the other hand, and recently in the centre of addiction research, is the involvement of cognitive self-control mechanisms in the pathogeneses of addictive processes. These so-called higher order cognitive functions operate on a more explicit, conscious level and deficits in their functionality seem to be one of the most robust findings in addiction research, replicated within a variety of different addicted populations. Specifically, these cognitive dimensions that reflect selfcontrol within an ecological, real life context such as decision-making are proposed to be a neuro-cognitive hallmark of addiction. Importantly, impairments in self-control have been related with a poorer course as reflected by treatment dropout and relapse.

However, it remains difficult to provide clear-cut interpretations to these findings. At least two fundamental questions remain as yet unresolved. First it is debatable whether deficits in self-control are specific to addictive processes or whether they represent a more global deficit underlying different disinhibitory pathologies. Second, it remains to be explored whether these deficits represent a vulnerability factor predating the development of an addiction or if they are a consequence of the (neurotoxicity) chronic substance use. Within the context of this presentation both questions will be discussed. Previous attempts to identify predictors for the treatment response in alcoholism have mainly concentrated on social and personality variables. Project MATCH was such an attempt which finally failed. The same holds true for similar attempts in pharmacotherapy. Therefore, we set out for a large oligocentre trial ''Project PREDICT' '. 432 patients are randomly assigned to treatment with acamprosate, naltrexone or placebo. At baseline patients are assessed with a battery of interviews, questionnaires and biological examinations (e.g. genetics). Specific emphasis is put on patients' individual pathways into relapse. It is determined whether relapse drinking represented a positive reinforcer (''reward craving'') or a negative reinforcer (''relief craving''). This is assessed with questionnaires, the startle reflex and fMRI. We hypothesize, that patients who are a priori identified as ''positive reinforcers'' better respond to naltrexone.

Negative reinforcers should benefit most from acamprosate. All patients have been included by now. Preliminary analyses suggest that it is possible to distinguish between the two craving types. The equivalent of positive reinforcement in the startle reflex correlates with fMRI responses to cues with a positive valence of about 0. 7. These methods might offer a platform for a targeted pharmacotherapy in alcoholism. The sense of self is important for mental health and several mental disorders are associated with abnormal experience of self. Major Depression involves an excessive self-focused attention, a tendency to engage oneself in self-referential processing and self-evaluation.

Depression is also associated with other cognitive biases leading to prioritize the processing of negative emotional information. In a series of recent cognitive and fMRI experiments we evaluated self processing and cognitive biases in depressed patients using memory paradigms.

In two studies we tested acute and remitted depressed patients with an Autobiographical Memory Task. Unlike controls, depressed patients retrieved repeated autobiographical events rather than specific events. Moreover positive emotional events retrieved by depressed patients were associated with a specific observer visual perspective. Overall these results suggest that acute and remitted depressed patients create discrepancy with their self for positive past behaviors, which maintains an incoherent and quite unfavorable view of their present self.

In a second study we used a self-referential memory task in depressed patients and normal controls coupled with fMRI acquisition. We found an increase activation of the dorsal Medial Prefrontal Cortex (DMPFC) in depressed patients compared to normal controls. Additionally, depressed patients displayed a greater activation of the left Dorso-Lateral Prefrontal cortex that was unique to the 'self' condition. Overall this activation pattern is consistent with the idea that increased self-focus in depression reflects a controlled allocation of greater cognitive resources during self-referential processing.

Taken together these findings suggest that the MPFC may subserve abnormal emotional processing and cognitive biases in depression. The MPFC may also be implicated in the onset and maintenance of low mood and in the increase vulnerability to develop a depressive episode in response to stressors. Emotions do not only serve to assign a particular value to objects or events forming the content of consciousness, but can directly influence perception and thus shape the content of consciousness and action. Functional neuroimaging studies in humans reveal neural mechanisms by which sensory and motor processes can be modulated by the affective significance of stimuli, and act in parallel to mechanisms of attention that are under conscious control. For instance, perception may be biased towards fearful relative to neutral faces, or towards angry relative to neutral voices, with enhanced activation of sensory brain regions involved in processing the corresponding stimuli (i.e., within visual or auditory cortex, respectively). Such enhancement in processing emotionally significant stimuli seems to depend on modulatory feedback influences from limbic brain areas such as the amygdala, which project directly to sensory cortical areas, and operate partly outside awareness. Amygdala activity can also influence motor output systems and thus contribute to attentional mechanisms underlying the interruption of current motor plans in the presence of threat signals. However, such activity in amygdala and other emotional brain areas may vary as a function of various individual factors, including anxiety and personality traits.

These data converge with animal and computational models indicating that the amygdala provides a neural system serving not only to register and learn about the affective relevance of stimuli but also to trigger appropriate reactions.

EMOTION AND COGNITION IN PERSONALITY DISORDERS Herpertz S.C. Rostock University, Dept. of Psychiatry and Psychotherapy, Rostock, Germany Individuals diagnosed with borderline personality disorder (BPD) are characterized by emotional instability with intense, rapidly rising emotions. They have been described as highly vigilant for social stimuli, especially for social cues that signal social threat or rejection and social situations have been shown to be potent triggers for emotional arousal and affective instability in BPD. Neurobiological data suggest that affective instability is associated with structural and neurofunctional abnormalities in the amygdala and its prefrontal interconnections, particularly the orbitofrontal and the anterior cingulate cortex, representing automatic and intentional aspects of emotion regulation. Affect dysregulation interacts with cognitive functioning prominently in two domains. On the one hand, inhibitory capacities, processed in the prefrontal cortex, have been shown to be restricted when emotional distractors have to be suppressed for the benefit of goal-directed behavior. On the other hand, increasing data suggest that emotional hyperreactivity interferes with the cognitive evaluation of social stimuli, e.g. facial emotion recognition, thereby leading to a specific pattern of altered emotion recognition in BPD. Behavioral and neuroimaging data is presented followed by the discussion of clinical implications and suggestions for future research. Introduction: Decoding emotional messages from faces is critical for survival and adaptation to our social environment. Abnormal patterns of response to emotional facial expressions have been observed in patients with schizophrenia as well as in subjects with aggressive behaviour or anxiety disorders.

Aim: To examine facial expression recognition ability and its neurobiological correlates in controls, patients with schizophrenia, their unaffected siblings and in healthy subjects with increased levels of aggressiveness or anxiety.

Subjects and Methods: Morphed faces depicting various intensities of facial expressions and gender were used as stimuli to investigate emotion and gender recognition abilities. We then used event-related brain potential (ERP) recordings to investigate the neural underpinnings of emotional and neutral face processing.

Results: Facial expression recognition was impaired in drugnaïve first-episode patients before and after neuroleptic medication [1] , and in remitted medicated patients [2] .

Unaffected siblings showed intermediate performance, suggesting endophenotypal characteristics. Gender recognition was preserved in all studies. Similar findings were obtained in patients with dementia (Frontotemporal and Alzheimer's Disease [3] ), and with Parkinson's disease [4] ). Cognitive [5] and cerebral mechanisms underlying these deficits are proposed, emphasising a particular role of frontotemporal connexions in schizophrenia [6] and a selective reduction in early frontal response to angry and fearful faces in subjects with heightened levels of aggressiveness or anxiety respectively.

Conclusion: Particular interest should be paid to intermediate vulnerability markers like emotion recognition that may increase risk for behavioural or psychiatric disorders. Introduction: Sleep regulation and hypothalamic-pituitary-adrenocortical (HPA) system function are associated with psychiatric disorders such as depression. However, most of the data available so far are from studies after the disorder's onset. Thus, we started a project in children aiming to investigate sleep regulation, HPA axis function, and psychological/behavioural variables in order to identify risk factors early in development.

Here, we report the first cross-sectional investigation.

Methods: 67 pre-schoolers (35 boys and 32 girls) at the age of 5 years underwent sleep EEG-monitoring according to standard procedures. Baseline HPA activity was assessed by the use of saliva morning cortisol measurements after awakening (MC), whereas saliva samples before, during and after psychological challenge were used to investigate HPA function under stress conditions.

Results: Boys showed significantly more REM sleep when compared to girls (p < .05).

Independent of gender, cluster analysis revealed that children labelled as bad sleepers (n = 27) showed significantly increased MC values compared to normal sleepers, whereas good sleepers displayed the lowest MC values. Sleep EEG markers such as an increased number of awakenings after sleep onset, more time in stage 1, 2, and in REM sleep were associated with increased cortisol values under stress conditions. Moreover, an increased sleep efficiency was significantly correlated with low degrees of impulsivity (p < .05), bullying and social inhibition (p < .05), whereas a decreased sleep efficiency was significantly correlated with the avoidance of perceiving social conflicts.

Conclusions: Our results show (1) that bad sleep is associated with heightened HPA system activity already in pre-school children, and (2) that unfavourable sleep patterns are related to more difficult behavioural/psychological dimensions. The longitudinal follow up will demonstrate if these biological abnormalities are predictive for the onset of clinically relevant psychiatric problems. The hypothalamo-pituitary-adrenal (HPA) system dysfunction is the most characteristic biological alteration found in a large proportion of severely depressed patients. The HPA axis is hyperactive and baseline cortisol levels are usually elevated, with alteration of the hormone secretion pattern. Accumulating evidence suggests that the combined dexamethasone (DEX)/corticotrophin-releasing hormone (CRH) test is highly sensitive to detect HPA system abnormalities in depressed patients. In one study, we evaluated whether the DEX/CRH test has a predictive value for the risk of depressive relapse in outpatients who are in clinical remission from a major depressive episode. Thirty-eight depressed outpatients (23 women, 15 men) in remission (MADRS score £ 8) underwent the DEX/CRH test and were followed for 12 months regarding the occurrence of a new depressive episode. Compared to a group of 24 control subjects, the group of patients who relapsed during the one year follow-up showed a statistically higher delta and AUC numbers for cortisol plasmatic values.

These results suggest that in outpatients who are in clinical remission from a major depressive episode, high delta and AUC values in the DEX/CRH test compared to control subjects can be associated with a higher risk of relapse. These results will be discussed in light of other recent clinical and preclinical studies. In elderly patients who suffer from depressive symptoms and cognitive impairment the clinical decision between the diagnoses of depression and dementia may be difficult. In addition, patients with dementia and depressed patients frequently show a disturbance of sleep. Sleep EEG registration in depression revealed a characteristic sleep EEG profile concerning distinct alterations of sleep architecture and REM-sleep (reduction of SWS, increase and advance of REM-sleep). In dementia polysomnographic assessment has been done less intensively, mainly in patients with dementia of Alzheimer type (DAT). The most significant polysomnographic finding in DAT is a reduction of REM-sleep, which may reflect impaired cholinergic neurotransmission. Therefore, predominantly REM-sleep variables clearly differ between depressed patients and patients with DAT. In this presentation polysomnographic data in dementia and depression will be reviewed. In addition, own long term studies in patients with different types of dementia and in depressed patients will be presented. The polysomnographic findings of these studies will be discussed with respect to differential diagnosis, prediction of treatment response and the long term course of both diseases. In addition, the results will be related to the current knowledge of the neurochemical and neurendocrine regulation of sleep. Investigating underlying genetics provides new insights into the molecular pathways of these endophenotypes and into the pathophysiology of depression vulnerability. We selected a high-risk linkage and endophenotype approach, i.e., we investigated REM sleep abnormalities (REM density) and altered HPA system regulation (dex/CRH test) in families with a high prevalence of major depression.

Methods: Eleven families were so far included, comprising 82 high risk family members. 32 of them were unaffected, 33 remitted, and 17 suffered from an affective disorder at the time of the investigation. Illumina Infinium Whole Genome genotyping with 100k bead chips was performed. Variance component (VC), and a quantitative trait linkage analysis (QTL) on polysomnographic (REM density) and neuroendocrine vulnerability markers (dex/ CRH test) were applied.

Results: Linkage analysis (VC, QTL) revealed suggestive linkage (LOD score > 2) for altered REM density at loci of the chromosomes 2, 4, 8 and X. The linkage results on chromosomes 2 and X correspond to previous findings. No results were obtained with a classical diagnosis based linkage approach.

Conclusions: The use of quantitative vulnerability markers in a high risk family study and a SNP based whole genome approach revealed a number of loci with suggestive linkage, that were not detectable with the classical linkage approach. Our findings suggest the suitability of investigating vulnerability marker in combination with a SNP based whole genome approach in complex disorders like depression. Three guidelines have been published on depression: Acute and continuation treatment of major depressive disorder 1 ; Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions 2 ; Treatment of unipolar depressive disorders in primary care 3 . WFSBP guidelines are developed by special WFSBP task forces which include members of the WFSBP as well as non-WFSBP colleagues seen as international experts in the relevant field. The task forces are composed with the aim to include knowledge and experience in the guidelines from every part of the world, not only the western hemisphere. The evidence criteria used in the preparation of these guidelines are adapted from the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. The core characteristic of these evidence criteria is that meta-analyses are not seen as the most important factors for a high grade of evidence, but the results of well-designed studies. This approach is closer to the decision process of the most important regulatory authorities such as the FDA or the EMEA/CPMP. The WFSBP guidelines on the biological treatment of major depression will be presented and discussed. The shift from normal affective behavior to affective dysfunctions is transient. Affective symptoms characterize most of the important psychiatric disorders, and as a consequence lack nosological specificity. They are nevertheless of high clinical significance and thus, knowledge of the neurobiological basis of the affective symptoms is of high importance in our quest for achieving better therapeutic accessibility. The amygdala, an essential key structure in the cerebral limbic network, is supposed to execute an evaluative associative function, combining external cues with internal responses thereby assessing and defining the valence, relevance and significance of stimuli. It is its extensive connectivity with various cortical and subcortical areas that enables fast automatic but also more conscious deliberate responses. As such it is also the focus of interest in our studies of the pathophysiological mechanisms of emotional impairments in psychiatric disorders. The direction research in this area has to take is to improve quality management, to obtain more detailed information about the neurobiological correlates of psychiatric diseases, to use new opportunities these improvements give not only to evaluate therapeutic intervention but to implement new therapeutic approaches. This may lead to a more detailed characterization of affective dysfunctions with the aim to improve diagnoses as well as therapy in patients.

EMOTION DYSREGULATION IN ADULTS WITH ADHD Stes S. Universitair Psychiatrisch Centrum K.U.Leuven, Kortenberg, Belgium

According to DSM-IV, the essential feature of Attention-Deficit/ Hyperactivity Disorder (ADHD) is a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. Although emotion dysregulation is not an essential feature, DSM-IV mentions possible 'associated descriptive features' such as low frustration tolerance, temper outbursts, mood lability and dysphoria. A competing diagnostic approach like the Wender Utah criteria for the diagnosis of ADHD in adults gives more importance to symptoms of emotion dysregulation. Besides a retrospective childhood diagnosis and ongoing difficulties with both inattentiveness and hyperactivity, a diagnosis of ADHD can be made in the presence of at least two of five other additional symptoms, among others: 'affective lability', 'hot temper, explosive short-lived outbursts' and 'emotional overreactivity'. Recently the British Association for Psychopharmacology published evidencebased guidelines for the management of ADHD in adolescents and in adults. They present an extended checklist of adult symptoms including 'irritability, impatience or frustration' and 'affective lability or hot temper'. According to different contemporary authors mood instability is extremely common in adult ADHD and can lead to diagnosis of minor affective disorders or personality disorders. However, this issue is controversial. According to McGhough and Barkley: ''permitting symptoms of irritability and hot temper to qualify one for the disorder creates an automatic confound of ADHD with oppositional defiant disorder, conduct disorder, and possibly the dysphoric form of bipolar disorder. Likewise, the inclusion of symptoms of mood lability without further clarification may further confound the delineation of this disorder from other mood disorders in adulthood''. In daily clinical practice we are thus confronted with differential diagnostic problems leading to different treatment options, in particular pharmacotherapy. In adults with ADHD, randomized-controlled trials with atomoxetine and methylphenidate OROSÒ have shown that symptoms of emotion dysregulation show a treatment response similar to other (core) ADHD symptoms. However, in case of a bipolar spectrum disorder these medications seem not without risk of inducing mania.

ADHD TREATMENT AND THE DEVELOPING BRAIN Konrad K. 1 Psychostimulants are the treatment of first choice in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). In addition, recently, a highly selective noradrenergic re-uptake inhibitor (Atomoxetine) has become available for the treatment of ADHD, which also effectively reduces symptomatology. The wealth of data supporting the short-term efficacy and safety of these drugs in the treatment of children is contrasted by a dearth of data on long-term effects of psychopharmacological treatment on structural and functional brain development. Rodent studies suggest that stimulants may persistently alter the dopaminergic system with long-term effects that extend beyond termination of treatment.

In this talk, long-term effects of ADHD treatment on the structural and functional brain development will be summarized. In particular, neuroimaging studies with children and adolescents with ADHD will be discussed. In addition, preliminary data on non-psychopharmacological treatment effects on the brain, such as behavioral interventions and neurofeedback procedures, will be included. Finally, clinical implications with regard to treatment protocols and prevention trials in children at risk for ADHD will be discussed.

TRANSLATIONAL APPROACH TO PSYCHOPATHOLOGY Do K.Q., Gysin R., Cabungcal J.H., Frank A., Lavoie S., Steullet P., Cuenod M. Center for Psychiatric Neuroscience, Dept. of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland Recent theoretical and empirical research on schizophrenia converges on the notion that core aspects of the pathophysiology of the disorder may arise from a disconnection syndrome that causes impaired communication between and within specialized brain areas. Moreover, converging evidence speak in favor of an abnormal susceptibility to oxidative stress in schizophrenia. A decreased level of glutathione (GSH), the principal non-protein antioxidant and redox regulator, was observed both in cerebrospinal-fluid and prefrontal cortex of schizophrenia patients. Moreover, patients have an abnormal GSH synthesis most likely of genetic origin: Two independent case-control studies showed a significant association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease-associated genotypes correlated with a decrease in GCLC protein expression, GCL activity and GSH content. These results suggest that GSH synthesis dysfunction represent a vulnerability factor in schizophrenia. Such a redox dysregulation during development could underlie the structural and functional anomalies in connectivity: In experimental models, GSH deficit induces anomalies similar to those observed in patients. (a) Morphology: decrease in normal spines in prefrontal pyramids and in GABA-parvalbumine but not of -calretinine immunoreactivity in anterior cingulate (b) Physiology: impairment of NMDA-dependant synaptic plasticity and of dopamine modulation of NMDA-induced Ca 2+ response. (c) Cognition: deficit in olfactory integration and in object recognition.

Conclusion: In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysfunction of GSH metabolism during development represent a major risk factor contributing to the disconnectivity syndrome in schizophrenia. Objective: Reduced left hemispheric lateralization for language was reported in schizophrenic patients but about 30% present an atypical lateralization i.e., a rightward asymmetry for language (Dollfus et al, 2005) . Consequently, in the present study we wanted to investigate the language network in the only patients showing a leftward lateralization for language.

Method: fMRI was performed as subjects listened to a factual French story alternated to the same story in Tamil. Subjects had to listen to and understand a story encompassing characters and social interaction. Twenty three pairs of patients (DSM-IV) and healthy controls matched on age, sex, level of education and handedness with leftward lateralization for language were selected. Signal variations were analyzed individually and by group comparisons.

Results: Schizophrenic patients presented significantly lower signal variations in the left medial superior frontal gyrus (MF1) than did controls (x=)6, y=58, z=20; Z score =5.6; p<0.001 uncorrected). Twenty-one out of the 23 (91.3%) control subjects but only 5 out of the 23 patients (22 %) demonstrated a positive signal variation in this area. In the multiple regression analysis, no clinical variable significantly explained the variance of the fractional BOLD signal values in the left MF1.

Conclusions: A left functional deficit was observed in a core region of the Theory of Mind network as patients were engaged in an ecological language task. This functional defect could represent a neural basis for impaired social interaction and communication in schizophrenic patients. Psychopathological phenomena may be related to disturbances of physiological brain circuits, like motor circuits for psychomotor disturbances or language loop for language related pathophysiological phenomena like auditory verbal hallucinations (AVH). Modern neuroimaging techniques like functional Magnetic Resonance Imaging (fMRI) and Electrical Source Imaging are technologies that are well suited to be used in the undertaking of understanding psychopathological phenomena e.g. in schizophrenia from a patho-physiological perspective. We have investigated the psychopathological phenomena of AVH in schizophrenic patients using fMRI, Diffusion Tensor Imaging (DTI), spontaneous and stimulus related electrical brain activity with the aim to understand why patients are so convinced about the external sources of their sensations and which brain structures are involved in the their generation. Hallucinating patients demonstrated partly a variable increase of blood flow, depending on the clinical picture and all of them showed an increase in the primary auditory cortex in the temporal lobe during hallucinations in a fMRI investigation.

During the hallucinations an increase of faster frequencies of the spontaneous EEG could be observed in the superior temporal lobe, faster EEG frequencies are commonly associated with increased mental processing. Additionally auditory evoked potentials suggested a reduced amplitude of the component N100, which is thought to be generated in areas in and around primary auditory cortex in the temporal lobe. DTI results, which depict the integrity of white matter connections in the brain, suggested an abnormally high neuronal coherence in the most important fibre tract connecting frontal and temporal speech areas (temporal section of the left arcuate fascicle). In summary these results indicate an increased activity of the early auditory cortices during hallucinations (contrary to findings demonstrated in healthy subjects during inner speech), which could be one mechanism responsible for patients conviction that their hallucinations are generated externally. Furthermore the results suggest that these pathophysiological mechanisms may be due to neurodevelopmental disturbances in language related physiological brain circuits. Besides the problem of drug-resistant depression, over the last decade the view has become increasingly widespread that achieving remission is just as important as response 1 . Follow-up data show very clearly that non-remitters have a much higher risk of relapse/recurrence or even chronicity than remitters. The problems of under-diagnosis and under-treatment of depression also need to be addressed. It is hoped that new mechanisms of action can overcome the limitations of traditional antidepressant medications. Unfortunately, some of the recent developments that raised the most interest either turned out to be less effective than hoped, such as the substance P antagonists, or did not yet lead to a drug likely to be marketed in the near future, such as CRF antagonists. On the other hand, the first melatonergic antidepressant, agomelatine, is a successful new development. Agomelatine is a melatonergic MT 1 and MT 2 receptor agonist with 5-HT 2C receptor antagonistic properties, and has shown antidepressant efficacy and favourable tolerability in several clinical trials in patients with major depression. Beside depression, anxiety disorders are one of the most common mental illnesses. Although anxiety disorders are treatable, less than 30% of sufferers seek treatment.

However, these disorders are associated with severe impairment, so identification of appropriate treatment options is imperative. Drug treatments include benzodiazepines, 5-HT 1A partial agonists, tricyclic antidepressants, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) 2 . The anticonvulsant pregabalin also appears promising for the indication of generalised anxiety disorder. In comparison to the benzodiazepines, the principal advantage of these drugs is that they have no risk of dependency. Drug development is evolving fast and is aided by improved brain imaging techniques, better animal models, and an increased knowledge of genetic markers. This should result in a change in the pharmacotherapy of depression, anxiety and psychiatric diseases in general, if not in the short term then certainly in the next 50 years. During the last decade war trauma research has emphasized the importance of secondary traumatization in the families of war veterans with posttraumatic stress disorder (PTSD). The purpose of the present study was to analyze secondary traumatization with regard to some important sociodemographic variables, prewar, war and post-war factors in the families of war veterans with chronic PTSD. A total of 89 families (89 males, 89 females and 124 children) were selected as the sample of the study. Secondary traumatization was analysed through retrospective analysis of medical records as well as with the scales of family functioning and Modified Secondary Traumatization Scale.

The results suggest that there is significant secondary traumatization in the families of war veterans with chronic PTSD, with severe problems in family and social functioning.

Symptoms of the secondary traumatization are similar to those of PTSD, but it is a different concept with specific pathophysiological mechanisms. Secondary traumatization are one of the main topic which should be taken into consideration in the treatment of the patients with chronic PTSD and in developing adequate treatment methods. Introduction and Aim: Although cross-sectional relations between depression or depressive symptomatology and dementia or cognitive impairment, have been exhibited by many studies, it is still unclear whether depression precedes subsequent dementia or vice versa. The purpose of our study was to explore whether depressive symptomatology is predictive of incident dementia 4 years later among the elderly subjects.

Sample and Methods: Longitudinal analysis in a survey of 9294 non-demented non-institutionalized elderly aged 65 years and over, in 3 French cities (Bordeaux, Dijon and Montpellier). Our working sample had a mean age (SD) of 73.7 (5.0) years, and included 60.7% of women. We performed logistic regression analyses of the relation between the level of depressive symptomatology assessed by the Center for Epidemiological Studies Depression (CES-D) scale at baseline, and at 2-year follow-up, and of Lifetime Major Depressive Episode (LMDE: assessed by the Mini International Neuropsychiatric Interview) and the incidence of dementia at 4-year follow-up. The main confounders were sex, age, education, hypertension, the Mini-Mental State Examination score at baseline, and psychotropic agents use.

Results: A high level of depressive symptomatology was not predictive of dementia 4 years later (adjusted OR CES-D high vs CES-D low = 1.6, 95% CI: 0.9-2.8). Likewise, no association between LMDE and increased risk of incident dementia was found. We observed a cross sectional association between the risk of dementia and concomitant high level of depressive symptomatology at 4-year follow-up, independently of the level of depressive symptomatology at baseline (adjusted OR CES-D high vs CES-D low = 2.0, 95% CI: 1.4-2.9 ).

Moreover, a high level of depressive symptomatology at 2-year follow-up was associated with higher risk of incident dementia at 4year follow-up (adjusted OR CES-D high vs CES-D low = 2.3, 95% confidence interval: 1.4-3.6) .

Conclusions: These results indicate a close temporal association between depressive symptomatology and increased risk of newonset dementia. We conclude that depressive symptomatology represents a prodromal state of a progressive disorder rather than a risk factor for incident dementia. The cross sectional association observed between depressive symptomatology and dementia illustrates the importance of adjusting for depressive symptomatology in epidemiological studies on cognition and/or dementia. Introduction: The Geriatric Depression Scale (GDS) was developed to rate depression in elderly. Its major advantages are that it is simple and fast (max. 10 min) to administer and that it does not require a trained interviewer. However, its reliability and validity in patients with cognitive impairment remains a matter of debate.

Aim: In order to determine the reliability and validity of the 30item GDS for the assessment of depressive symptoms in Mild Cognitive Impairment (MCI) and probable Alzheimer's disease (AD) as compared to the Cornell Scale for Depression in Dementia (CSDD), we set up a prospective study.

Methods: Diagnosed according to strictly applied diagnostic criteria, patients with MCI (n=156) and AD (n=247) were enrolled. At inclusion, depressive symptoms were assessed by means of the GDS and the CSDD. Patients underwent a neuropsychological examination that consisted of amongst others a Mini-Mental State Examination (MMSE) according to which the AD group was subdivided in mildly (MMSE ‡18) (n=117), moderately (MMSE<18 and ‡10) (n=89) and severely affected (MMSE<10) (n=38) AD patients. As a CSDD total score of 8 or more suggests significant depressive symptoms (Burns et al., 2004) , this cut-off score was applied to dichotomise the patients included for ROC curve analysis.

Results: In MCI, moderate but highly significant correlations were found between GDS and CSDD scores (Spearman: r=0.615; P<0.001). In mildly (r=0.313; P<0.001), moderately (r=0.229; P=0.031) and severely (r=0.336; P=0.039) affected AD patients, only weak correlations between GDS and CSDD scores were calculated. ROC curve analysis showed that sensitivity and specificity values of respectively 95% and 67% were achieved when a GDS cut-off score of 8 was applied in MCI patients. In AD patients, too low sensitivity and specificity values did not allow selecting an optimal cut-off score by means of ROC curve analysis.

Conclusion: The GDS is a reliable screening instrument for depressive symptoms in MCI patients. Using a cut-off score of 8, sensitivity values of 95% were achieved. Introduction: Pathological gambling (PG) is an impulse control disorder previously reported to complicate dopamine agonist therapy in Parkinson disease 1 . It has not been described in schizophrenia with dopamine partial-agonist. We report a patient with a schizo-affective disorder who developed PG while receiving aripiprazole (dopamine partial-agonist).

Patient: Mr. X is a 30 years-old patient with a history of schizoaffective disorder for 13 years. His symptomatology remained stable under a regimen of risperidone (4 mg/day) and carbamazepine (800 mg/day) for 10 years. In september 2005, aripiprazole (15 mg/day) was introduced as riperidone was discontinued secondary to an important weight gain for further years. He started to develop PG after a few days. There was no exacerbation of psychotic or mood symptomatology as attested by psychopathological scales. Despite a cognitive and behavioral therapy, the symptomatology of PG worsened. In april 2006, we suspected aripiprazole to cause this adverse reaction. In May 2006, he presented a dystonia.

Aripiprazole was finally stopped and risperidone (2 mg/day) reintroduced. PG fully disappeared a few days later.

Discussion: PG has already been reported as a complication of dopamine agonist in Parkinson disease 1 . In the case of Mr. X, PG occurred with dopamine partial-agonist. PG should have been caused by stimulation of the mesocorticolimbic pathway whereas dopamine antagonist (risperidone) has been abruptly stopped. Our clinical observation strengthens the hypothesis that PG is caused by an altered function of the dopaminergic reward system 2 . It should also be noticed that Mr. X presented recreational gambling and nicotine dependence which could be risk factor for PG.

Conclusion: To our knowledge, it is the first time that PG is described secondary to dopamine partial-agonist therapy in schizophrenia. It emphasizes the pivotal role of dopamine neuromodulation in PG 2 . Introduction: Many neuro-psychiatric diseases are characterized by a significant peripheral enhanced formation of reactive oxygen species (ROS). ROS has a microbicidal action since the host defence function through high ROS-concentration has a direct toxic effect on bacteria. Systemic application of LPS results in enhanced inflammatory processes (e.g. increased IL-6 levels) characterized by a stimulation of neutrophils and macrophages or impairment of brain function.

Aim: The aim of this study was to analyze the effect of NOS inhibition on LPS induced formation of ROS in hippocampal neuronal cells in vitro and in the striatum of the mouse via microdialysis.

Methods: In vitro experiments: Mouse hippocampal HT22 cells were treated with LPS (100ng/ml) or LNAME (1 mM) or IL-6 (2ng/ ml), and 0.8mM CMH for 3 hours. The cells were then scraped from the dishes and immediately frozen in liquid nitrogen. ROS was detected by electron spin resonance spectroscopy (ESR). In vivo experiments: Microdialysis probes were implanted into Balb/c mice with stereotactic technique one week before the experiments. Central nervous ROS was measured using CMH, infused via microdialysis probe (1.5 ll/min) as spin label and detected by ESR. The experiments were started by CMH infusion with or without a preliminary injection of L-NAME (i.p. 10 mg/kg). A 2 hour control period was followed by a 3 hour LPS (i.p., 100 lg/kg) or IL-6 (3ng/ min) infusion. Sampling time was 30 min.

Results: In vitro experiments: Incubation with LPS revealed a significant increase in ROS formation whereas incubation with LPS + L-NAME, IL-6 and IL-6 + L-NAME induced a non-significant increase in ROS formation in hippocampal mice cells. In vivo experiments: Treatment with LPS or IL-6 increased significantly ROS formation in the striatum of conscious mice. No significant effects were found after treatment with L-NAME and LPS + L-NAME.

Conclusion: Both sets of experiments revealed a significant increase of ROS formation after treatment with LPS which was reversed by additional L-NAME treatment. IL-6 also stimulated ROS formation in vitro and in vivo. ROS formation can be blocked by LPS through NOS inhibition which might protect against brain damage in septic shock.

Introduction: There is increasing evidence that cases of therapy resistant depression are related to or associated with immune inflammatory abnormalities, the etiology of which remains usually obscure. We accumulated evidence that in a subgroup of such cases bacterial hearths may serve as triggers of an inflammatory or autoimmune upregulation, eg. cytokine and other inflammatory abnormalities, to induce depressive symptoms.

Method: Case observations during the last 10 years within a general long-standing research approach on immune inflammatory abnormalities in depression, led to identification of interesting single cases, in which specific etiologies were made plausible from clinical, laboratory and other findings, assessed over the long-term and related to the clinical course.

Specific treatment approaches were related to positive therapeutic responses.

Results: Laboratory findings (antibodies against streptococci, autoimmune antibodies) investigated in blood and selectively in cerebrospinal fluid, were followed over the long-term in blood and/ or CSF. These findings were related to brain imaging and therapeutic procedures, such as tonsillectomy or specific dentistry treatment respectively surgery. Such approach resulted in single case identification of relevant bacterial hearths. In 1 case of streptococcal associated depression specific antibiotic therapy with Penicillin V combined with tonsillectomy was successful (Bechter et al 2007) . Case follow-up was possible in 3 cases, in 1 case over more than 5 years, and showed dramatic improvement after hearth sanitation (hearths were tonsilla or teeth or jaw).

Conclusion: Preliminary findings of treating relevant bacterial hearths are intriguing and important because even severe therapy resistant depression resistant over years before could completely remit after specific treatment. The problem is that several bacterial agents may be involved appearing as mixed infections. There is a gap of understanding of the role of hearths, though such infections are frequent. There is some impression, that repeated reactivations may increase the risk of psychiatric disease presumably from an increasing prevalence of autoimmune mechanisms (eg. epitopespreading). Elimination of triggering bacterial hearths in time may therefore prevent some psychiatric disorders. were treated for schizophrenia, 39% for mood disorder and 32.60% for other psychiatric conditions. Patients had a mean illness duration of 11.17 years (0-50 years) and dual diagnosis was not infrequent. Most patients were taking an antipsychotic drug (84.16%), 60.88% an antidepressant and 33.21% a mood stabilizer. Mean waist circumference at start was 103,77 cm (men) and 100,82 cm (women) and changed little with the men (103,17 cm) however a diminution was seen with the women (98,55 cm). Glycemia stayed stable over time (baseline: 98,46 mg/dl; end: 99,61 mg/dl). A similar trend was seen regarding the blood pressure (Systolic at start: mean 12,43 cm Hg at end: 12,29 cm Hg / Diastolic at start: 7,47 cm Hg at end: 7,43 cm Hg. Cholesterol, HDL, LDL and triglycerides stayed stable during the program period as well. Sixty-two percent of the patients felt the program helped to improve their psychological functioning, 68,45% found the program helpful in controlling their weight and 78,36% attributed feeling ''better'' to the program.

Conclusion: Lifestyle programs can be successfully adapted for patients with psychiatric disorders; Women seem to be more open to ''healthy'' life style changes. Overall a stabilization of metabolic risk factors was noticed. Patients contributed their improved general and psychological wellbeing to this program. Introduction: Many neuro-psychiatric diseases are characterized by a significant peripheral enhanced formation of reactive oxygen species (ROS). ROS have a microbicidal action since the host defence function through high ROS-concentration has a direct toxic effect on bacteria. On the other hand low ROS-concentrations stimulate cell proliferation through activation of redox-sensitive intracellular signalling mechanism. The intracellular mechanisms on metabolic activity and the interaction with ROS have not been sufficiently studied.

Aim: One of the most important regions of the brain is the hippocampal area which is responsible for memory and behaviour. For this reasons, we analyzed the formation of ROS induced by haloperidol, clozapine, and olanzapine in hippocampal HT22 cells.

Methods: Mouse HT22 cells were cultured at a final density of 900.000 cells/well in DMEM, 10 % FCS, 2 % NaPyruvate, 1 % antibiotic-antimycotic medium. Prior the experiments, medium was substituted by a Krebs-Ringer solution, pH7.4 and 5mM glucose. After 3h incubation with haloperidol, clozapine, or olanzapine (each 20 lg/2ml) and 0.8mM CMH, the cells were detached by trypsin and immediately frozen in liquid nitrogen and stored at )80°C until measurement. ROS was detected by electron spin resonance spectroscopy (ESR) at )190°C.

Results: All antipsychotics enhanced the formation of ROS in HT22 cells. Clozapine significantly increased the ROS concentration, whereas the enhancement of olanzapine and haloperidol did not reach significance.

Conclusion: These in vitro experiments revealed that the antipsychotics under investigation increase the reactive oxygen speciesconcentration after short-term incubation. Disturbances of the HPA axis are observed in anorectics (AN) (Brambilla, et al., 1996) and bulimics (BN) (Pirke et al., 1993) . Furthermore, body image distortions and dissatisfaction (Cash& Deagle, 1997) as well as depression (Thiel, 2004) are characteristics of both types of eating disorder. Therefore the questions were asked: 1. if cortisol, body image disturbances and degree of depression and their therapy induced changes differ between AN and BN; 2. if the three measures and their changes are differently related to each other in AN and BN.

Method: 19 anorectic and 16 bulimic young women were tested at the beginning and end of an 8 week in-patient psychotherapy. The computer based Body Image Assessment System (Letosa-Porta et al, 2005) was used to measure distortion (DIST= perceived -real body measures) and dissatisfaction (DISSAT= desired _ perceived measures). Also changes of questionnaire based depression scores and of saliva cortisol awakening responses (CAR) were compared between AN and BN and were intercorrelated separately in the two groups.

Results: Revealed that BN had more pronounced initial DIST and DISSAT scores than AN and exhibited larger reductions of these after therapy. CAR values were higher in AN than in BN and changed in opposite directions during therapy, which was correlated to weight gain in AN. The two groups had similar initial levels and therapy induced reductions of depression scores. But only in BN, not in AN initial depression scores were significantly correlated with DISSAT. Changes in body image disturbances were not related to changes in depression.

Only in AN, not in BN therapy induced decreases in depression were accompanied by reductions of the final increase of the CAR.

Conclusion:

The data indicate that misperception of and dissatisfaction with one's figure is more pronounced in BN but that BN females perceive themselves as less overweight after therapy while AN have a more realistic view of their figure throughout. Higher cortisol levels in AN might reflect the metabolic changes due to starvation, whereas correlations of CAR with DISSAT in BN and the parallel changes of depression and CAR levels in AN may reflect the association of a disturbed HPA axis with depression.

MEDICATION OVERUSE HEADACHE: IS IT PART OF THE ADDICTIVE SPECTRUM? Radat F. 1 , Creac'h C. 2 , Guegan-Massardier E. 3 , Mick G. 4 , Guy N. 5 , Fabre N. 6 , Giraud P. 7 , Nachit-Ouinekh F. 8 , Lanterri-Minet M. 9 1 Chu Pellegrin, Bordeaux; 2 Hôpital Bellevue, Saint Etienne; 3 Chru -Hôpital Charles Nicole, Rouen; 4 Ch, Voiron; 5 Chu Montpied, Clermont Ferrand; 6 Chu Rangueil, Toulouse; 7 Ch Annecy; 8 Glaxo-SmithKline Company, Marly Le Roi; 9 Chu Hôpital Pasteur, Nice, France Introduction: Medication overuse is present in one third of chronic headache patients, who therefore suffering from medication overuse headache (MOH) (1). Psycho-behavioural disturbances are a major issue in those patients.

Aim: The objectives of this study were (a) to estimate the proportion of patients with MOH presenting DSM IV dependence criteria on acute headache medication (AHM) and (b) to identify variables associated with this diagnosis.

Patients and Methods: The study included consecutive patients with MOH in seven tertiary care centres in France.

Results: Two hundred and forty seven patients with MOH were identified, of whom 165 (66.8%) fulfilled DSM-IV (2) dependence criteria for AHM.

Multivariate regression analysis identified six variables associated with this diagnosis: overuse of opioid analgesics, overuse involving several pharmacological classes of AHM, antecedents of medication withdrawal, current chronic headache with migrainous features, antecedents of migraine, and comorbid dependence on benzodiazepines, caffeine or tobacco.

Conclusion: These results show that two-thirds of patients with MOH referred to tertiary care present behavioural dependence on AHM. Treatment of such patients should always involve a psychobehavioural intervention. Moreover, these results emphasise the deleterious effects of opioid analgesics in headache patients. Finally the association of dependence on AHM with dependence on other psychoactive substances suggests that MOH contributes to the addictive spectrum in some patients. Introduction: Cloninger's type II is a severe, early-onset, malelimited, genetically influenced, impulsive form of alcoholism. Significant association has been reported between the A1 allele of the DRD2, substance misuse and personality traits of impulsivity and novelty seeking, while the short allele of the 5-HTTpro may as well influence both the severity of the disease and impaired behavioral control in alcoholics.

Aims: We assessed the association of two gene polymorphisms (TaqI A DRD2 and 5-5HTTpro) with Cloninger's typology, as defined by age at onset of alcohol-related problems, and family history of alcohol abuse, which is thought to be more frequent in type II alcoholics.

Patients and Methods: 58 male alcohol dependent patients were discriminated according to age at onset of alcohol-related problems and interviewed about family history of alcoholism.

Genomic DNA was extracted and PCR amplifying the studied polymorphisms were performed. The associations between DRD2 (A1 or A2 alleles), 5-HTTpro (L and S alleles), family history and typology were assessed by Pearson chi2 analyses.

Results: While typology was not influenced by any of the studied polymorphisms, a higher rate of general family history of alcohol abuse was still observed in type II patients (v 2 1 = 4.53; p = 0.033). Furthermore, the A1 allele of the DRD2 was significantly associated with paternal history of alcoholism (v 2 1 = 4.66; p = 0.031) and male, first-degree, collateral history of alcoholism (v 2 1 = 4.40; p = 0.036).

Conclusions: Age at onset as main discriminator between type I and type II does not seem to be influenced by TaqI A DRD2 and 5-5HTTpro polymorphisms. However, the A1 allele of the DRD2 may be a marker of male familial alcoholism, which is in line with previous studies showing association between TaqI A DRD2 with some clinical features of type II alcoholism. Introduction: The association between suicidal behaviour and aggressive behaviour towards others is assumed to rely on a shared trait-dependent vulnerability. Studies exploring impulsivity, aggression and anxiety as common susceptibility factors, show contradicting results. Aim: We investigated the role of trait anxiety, aggression and impulsivity in the development of suicidal and aggressive behaviour.

Patients and Methods: Patients, who were admitted to the psychiatric ward following a suicide attempt or aggressive behaviour towards another, were included. Anxiety, anger, aggression, impulsivity and depression were assessed using self-report questionnaires. Trait personality dimensions were assessed using Cloninger's Temperament and Character Inventory.

Results: The study population consisted of 79 patients, of whom 30 patients had only a history of suicidal behaviour, 15 patients had only a history of aggressive behaviour, and 34 patients had a history of both behavioural problems. No significant between-group difference was found for state-dependent characteristics. The three subgroups scored higher than normal on trait anxiety, indirect aggression and impulsiveness according to the Barratt Impulsiveness Scale, with no group effect. A between-group difference was found with regard to direct aggression, indicating normal levels for the suicidal-only group and increased levels for the other subgroups. Patients with a history of both behaviours had higher scores on impulsivity as a personality dimension in comparison with the other subgroups. Among patients with a history of aggressive behaviour toward others, only those with also a history of suicidal behaviour had elevated scores on Cloninger's anxiety-measures.

Conclusion: These findings indicate that high temperamental impulsivity is no prerequisite for suicidal behaviour, while high anxiety does not protect against aggressive behaviour.

As indirect aggression refers to biased perception of emotional information, we hypothesize an increased tendency to perceive or interpret situations as defeating as a common vulnerability to suicidal and aggressive behaviour. Studies in larger samples are needed. A., Plutchik R., van Praag H.M., 1993. Anxiety, impulsivity and depressed mood in relation to suicidal and violent behavior. Acta Psychiatrica Scandinavica 87 (1) Introduction: Depression or minor elevations in depressive symptoms significantly increase the risk of incidence of coronary heart disease among previously healthy participants or worsen the cardiac prognosis in patients with established coronary heart disease.

The scientific evidence is strongest for patients who have been hospitalised for an acute coronary syndrome (ACS) that is, myocardial infarction or unstable angina (1). Although anhedonia, one of the main symptom of depression (4), is associated to elevated mortality in major depressives (2) or in medical inpatients (3) its role has not been explored in subjects hospitalised for ACS. Aim: The purpose of the study is to test the hypothesis that anhedonia would predict mortality and cardiac morbidity in subjects hospitalised for ACS.

Patients and Method: 293 subjects hospitalised for ACS were included in the study. At admission they filled out several rating scales including the revised Physical Anhedonia Scale (PAS). All the subjects were followed during three years. Mortality, onset or recurrence of myocardial infarction, recurrence of unstable angina, onset or increase of cardiac insufficiency, other cardiac events were recorded. Using the cutoff of 19 on the PAS, the subjects were distributed into a anhedonic group (PAS>19) or a hedonic group (PAS<19).

Adjusted Odds ratio (OR) were calculated at the first half of the first year, the second half of the first year and after the first year. Adjustments took into account sex, age and previous history of ACS, obesity, smoking, diabetes mellitus, hypertension, hypercholesterolaemia, familial history of ACS.

Results: At the second half of the first year and after the first year the risk of recurrence of unstable angina were significantly increased, the adjusted odds ratio were respectively: OR = 2.01 (p = .038) and 2.84 (p = .02 ). At the first and second half of the first year and after the first year the risk of onset or increase of cardiac insufficiency was significantly elevated (OR higher than 4 (p < .05) for the three evaluations.

Conclusion: Anhedonia could constitute a useful indicator of cardiac morbidity following ACS. The practice of evidence-based medicine makes it necessary for the DSM classification system to re-examine if Major Depression has got objective physical signs occurring with some consistency and should these be included among the diagnostic criteria. In Major depression one may observe retardation of movements and diminished gestures and expressions. There is often a combined sense of inner restlessness, of unquiet brooding. The patient may appear tired, self-concerned, bored, and inattentive and display a loss of interest in the surroundings. Anxiety is a conspicuous and an integral element of affective state and may be expressed by severe restlessness and agitation. Anxiety can be so profound that the diagnosis of depression can be a matter of speculation only. Muscle tension, wringing of hands, weeping and moaning, repeating over and over in a monotonous and stereotyped way phrases expressive of misery are all important clinical signs of Major depression. Similarly tachycardia, dry tongue/mouth, sweaty palms and/or bodily extremities, cold clammy skin, pallor, pupillary dilatation, tremor, and the fluctuations in blood pres-sure with wide pulse pressure are all important that give away the underlying distress.

The DSM-IV neglects to include physical signs as an integral part of the clinical picture of depression. DSM-IV requires the presence of only five of the nine criteria in group A for the diagnosis of Major depression without measuring their severity. These are symptoms which are subjective (depressed mood, diminished interest, insomnia, loss of energy feelings of worthlessness and recurrent thoughts of death) and Hamilton reported these symptoms occurred in 75-100% of the general patient population. Hamilton, in designing his rating scale explained and specified that first factor is a general factor of depressive illness measuring the severity of symptoms and the crude total score on the rating scale co-related with the first factor to the extent of 0.93. Wilhelm and colleagues had confirmed that psychomotor disturbance, comprising slowed mentation, movements and speech, as the core clinical feature melancholic depression.

As at present the diagnosis of Major depression is based on most commonly occurring symptoms, without having attained certain severity, then possibly patients with non biological unstable symptoms, with homeostatic responses and no pathological processes' who may respond to interventions rapidly easily find a diagnosis of Major depression. This could also explain a large placebo response and a narrow therapeutic response in recent randomised controlled clinical trial. Furthermore, since in most such clinical trials HDRS was used to measure the therapeutic response it may be considered that the use of HDRS was not in accordance with the diagnostic practice that HDRS proposes to follow. Hence it is possible that in recent years a truncated use of the HDRS has occurred in research on Major depression. This view requires a further examination. Bagby et al draw the inference that HDRS is flawed and has become lead weight as it only partly relates to the operationalization of depression in DSM-IV. The reverse should be the case. The onus should be on the DSM classification system to revise the diagnosis of Major depression and to include the physical signs. This would also help exclude depressions with unstable pathologies, day to day and homeostatic upsets. Introduction: Impulsivity is being recognized as a core feature of bipolar disorder, as much as a state as a trait. Although very few studies have focused on this relationship, it has been suggested that exploring its neurobiology could help to elucidate the pathophysiology of this illness. Impulsivity and aggression have been considered key factors in suicide attempts, and together with sensation seeking it appears strongly linked to substance abuse which, in turn, may increase impulsivity, facilitating comorbidity.

Aim: To assess the relationship between impulsivity, aggression and sensation seeking with different clinical variables of bipolar disorder.

Patients and Methods: Barratt Impulsiveness Scale (BIS-11), Sensation Seeking Scale (SSS) and Buss-Durkee Hostility Inventory (BDHI) were administered to 69 bipolar out-patients (42 bipolar I and 27 bipolar II) which remained euthymic and without a history of substance abuse for six months or more, with no medication changes for at least two months. History of past suicidal behavior, sociodemographic and clinical data were also obtained.

Results: Type II bipolar patients scored higher on total BIS and motor subscale, as well as on the BDHI physical aggression subscale. No statistically significant differences appeared in the SSS. Patients with predominant depressive polarity through the course of illness had higher global scores on total BDHI and irritability and suspiciousness subscales, while manic polarity scored significantly higher on the SSS experience seeking subscale. Prior history of suicide attempts showed no significant statistical differences in any of the scales.

Conclusions: Stable I and II bipolar patients without active substance use show some differences in impulsivity and related features as aggression and sensation seeking. These data would merit further investigation and could help more accurate diagnosis and treatment. The predictive component of smooth pursuit has been studied by comparing the gain during predictable (pure sinusoid) and unpredictable (pseudo-random stimuli composed of a mixture of sinusoids of different frequencies) target motions.

The aim of this experiment was to study the predictive component of smooth pursuit in schizophrenics as compared with controls.

Fifty-one schizophrenics (DSM IV, categorized into deficit and nondeficit subgroups) and twenty-one controls were studied. During a predictable task, subjects were asked to track a target which moved in horizontal sinusoidal waveform at 0.4 Hz. The sinusoidal pursuit gain was calculated. For the unpredictable task, the target motion was composed of five sinusoidal waveforms moving at respectively 0. 1, 0.2, 0.4, 0.6 and 0.8 Hz. The pseudo-random pursuit gain was calculated for each subject and each frequency. The mean sinusoidal pursuit gain was significantly decreased in schizophrenics as compared to healthy controls with no significant differences between patient's groups. During pseudo-random task at 0.4 Hz, the gain was similar for all groups. The gain was higher during predictable target as compared to pseudo-random stimulus at 0.4 Hz. No correlations were found between the gain and any clinical variables.

These results mean that schizophrenic subjects, whatever their level of negative symptoms, are not impaired in their pursuit performances per se when there is no need for prediction of the target movement. Introduction: Aetiology of schizophrenia remains unknown. Maternal smoking during pregnancy may be associated to further behavioural disorders. The purpose of this study was to determine whether an increased prenatal smoking exposure is associated with schizophrenia.

Method: We have carried out a retrospective epidemiological study to compare tobacco use during pregnancy between mothers of schizophrenic or schizoaffective patients recruited in our psychiatric hospital (DSM IV criteria) and mothers of non psychotic matched patients recruited in the emergency ward of our hospital. The relative risks were calculated using odd ratios with a confidence interval of 95 %.

Results: 100 schizophrenic patients (Group A: 74 males, 26 females; mean age 33.5 +/) 9.3) and their mothers were interviewed. One hundred non schizophrenic subjects, matched for age and gender, were interviewed (Group B: 72 males and 28 females; mean age 34 +/) 9.8) .

The mothers' ages did not significantly differ between both groups, as well as their age at the time of pregnancy. Concerning tobacco use, significantly more smokers were observed in group A (73%) as compared with 57% in group B (chi2 = 6.379, p= 0.041*). The age at onset for tobacco consumption and the daily amount of tobacco smoked did not significantly differ between both groups. There was no significant difference between the amount of tobacco smoked during pregnancy among mothers of group A as compared with mothers of group B (p=0.063).

Conclusion: This study aimed at showing the prevalence of tobacco use among mothers of schizophrenic and schizoaffective patients as compared with that of mothers of non psychotic patients. We have found no significant difference between the amounts of tobacco smoked during pregnancy when the two groups of mothers were compared. This suggested that tobacco use during pregnancy did not constitute a risk factor either for schizophrenia or for further tobacco use among schizophrenic patients. Introduction: There is substantial evidence that maternal smoking during pregnancy is more frequent in Attention Deficit-Hyperactivity Disorder (ADHD) children than in normal control subjects. We decided to compare smoking history of parents of ADHD children with smoking history of parents of children who were not normal control subjects: anxious children and children suffering from general health diseases (GHD).

Patients and Methods: Thirty mothers of ADHD children, 30 mothers of anxious children treated for social phobia and 30 mothers of children with nephrological disorders were compared. Subjects were recruited in the same clinical child psychiatry and pediatric out-patient setting (Hôpital Robert Debré, Paris). Structured clinical interview of the mothers were conducted, recording retrospective data. Paternal smoking was assessed through proxy interviews of the mothers.

Statistical Analysis: Smoking habits were described before pregnancy, during pregnancy, post-partum and currently. Smoking history of mothers and fathers was compared using repeated measures ANOVA and pair-wised t tests. Possible confounding factors (maternal age, educational level, alcohol consumption level, maternal psychiatric care, delivery complications, APGAR score, child age), were compared using khi 2 and ANOVA.

Results: Smoking histories of mothers and fathers were different according to child's diagnosis (p = .031 and p = .011). Smoking cessation during pregnancy was less frequent in ADHD mothers than in the two other groups (6.6% vs 36.7% and 26.7%, p = .011). Groups were not different when compared according to the possible confounding factors.

Conclusion: Smoking exposure during pregnancy was higher among ADHD children because of two factors: lower maternal smoking cessation and higher paternal smoking rate. Barakol, 3a, 4-dihydro-3a, 8-dihydroxy-2, 5-dimethyl-1, 4-dioxaphenalene, is a purified extract from Cassia siamea, a plant that has been used in Thai traditional medicine for the treatment of insomnia, constipation and hypertension. The objective of this present study was to investigate the role of early life stress, social isolation rearing from weaning on the anxiolytic effect of barakol.

Methods: Male Wistar rats were weaned at 21 days and housed either singly or in groups of 6 in the same room. Five weeks later, behavioral testing for their sensitivity to the anxiolytic effect of barakol was started by using the open field test.

Results: The results from the open field test showed that under normal light (50 lux), pretreatment with barakol (5, 10 and 25 mg/kg, i.p.) did not significantly induce the anxiolytic effect in both isolation and socially reared rats compared with the saline treated control rats. However, under high light (500 lux) this compound significantly produced a dose-related anxiolytic effect in socially reared rats, as indicated by decrease the number of entry and time spent on the inner zone (P<0.05), but the anxiolytic-like effect of barakol (5, 10 and 25 mg/kg, i.p.) was not observed in the isolation reared rats.

Conclusions: These results indicate that barakol has anxiolytic effect in social reared rats only under stress condition (high light). Early life stress, social isolation rearing from weaning prevents the anxiolytic effect of barakol.

References 1. Wongwitdecha, N. and Soo-ampon, S. (2007) World J. Biol. Psychiat. 8(Suppl 1):192. 2. Wongwitdecha, N., Ritilert, P., and Verawatanapakul, V. (2004) The International Journal of Neuro-psychopharmacology 7(Suppl Introduction: The diagnosis and treatment of cancer can be an extremely stressful and possibly traumatic experience. Cancer has been recognized as a traumatic event capable of precipitating posttraumatic stress disorder (PTSD) in DSM-IV. However, recent researches have documented that a broad range of both positive and negative psychosocial outcomes might follow cancer diagnosis and treatment. Evidences suggest that cancer might precipitate both posttraumatic stress and posttraumatic growth, at times within the same individual. Aim: In this study we investigated the prevalence of PTSD and posttraumatic growth in a sample of cancer patients.

Methods: Hundred patients diagnosed with cancer (53 women and 47 men) who attended to oncology outpatient units were randomly recruited to the study. PTSD is assessed with ''Structured Clinical Interview for DSM-IV (SCID) -PTSD Module'' and posttraumatic growth is assessed with ''Stress Related Growth Scale''.

Results: Although 19% of the sample met diagnostic criteria for PTSD, there was not any statistical significance between diagnosis of PTSD and sociodemographic variables such as gender, age, marital status, level of education, occupation, social support, residential area and having a child. Treatment with chemotherapy and PTSD was significantly correlated. Suicidal thoughts were detected in 11% of the patients, although there was no patient with the history of suicide attempt. Mean posttraumatic growth score was 124.1 ± 22.8 and there was not any significant association between posttraumatic growth score and the gender and ages of the patients. On the other hand, religious and/or spiritual belief either increased or stayed the same in 80% of patients. Most of the survivors indicated that their spirituality and faith assisted them throughout the cancer experience.

Conclusion: The presence of PTSD in cancer survivors probably influences the patient's use of healthcare resources and it may affect the clinical outcome. Early recognition of PTSD in the patients diagnosed with cancer is important for ensuring the receipt of timely and appropriate clinical interventions. Nevertheless, many cancer survivors experience positive growth as they adjust to changes brought about by their illness. In particular, religious and spiritual faith provides patients diagnosed with cancer with important tools for coping with their illness and should be recognized by diagnosing physicians. Future research should refine current screening procedures and develop interventions to better address either PTSD or posttraumatic growth in cancer survivors.

Introduction: Hormonal interaction with the functioning of the central nervous system has been well known for a long time. Typical examples are the thyroid hormones (mood disturbances) or the sexual hormones (menopause, premenstrual syndrome)(1). The result of big, exceeding the normal hormonal changes, processes is different psychic disturbances.

Some disturbances in the hormonal system were also reported with schizophrenia or anorexia (2) .

Aim: The aim of the study was concluding whether one could find the disturbances in the sphere of psychic functioning in the menstrual cycle. If it could be proved that such a correlation exists, it could mean that the reaction of hormones on psychic state is strong enough that even small variations in the physiological levels contribute to disturbing psychic efficiency.

Patients and Methods: The study based on Stroop test and lateralisation index basing on CV test (dichotic listening -consonant vowel). The study encompassed 28 healthy women at the age of 19 and 20, All women were healthy and without the history of psychic illnesses in the families. They were all right-handed which was confirmed with EHI and Goryn & Dudeck tests. No woman was on the oral contraceptives or other drugs. Each woman was examined 5 times during 4 weeks period, every week. The reference in time was the onset of menstruation cycle.

Results: In the peri -ovulation period the value of the lateralisation index is the lowest. The reverse dependence is noticeable in the number of the errors done. No similar dependence is confirmed in Stroop test.

Conclusion: The middle of the menstruation cycle is the period of hormonal storm, and > the advantage pattern of the dominating hemisphere changes. Proving this, > however, requires further studies. Introduction: Social phobia is an anxiety disorder defined by excessive fear reactions that are triggered by social or performance situations in which the person is exposed to possible scrutiny by others. In social phobia, gaze aversion could be a central component of the etiology of social phobia and most of the cognitive and behavioral therapy programs take into account this into account. The emotions of the people around a social phobic person seem to model this gaze aversion. Only one study has to date shown objectively gaze avoidance in social anxiety (Horley et al., 2004) , and no study on the effect of gender had yet been done prior to our research.

Aim: Our research consists of testing gaze aversion in social phobia subjects compared to control subjects in different emotional faces of men and women and according to the gender of the participants.

Patients and Methods: Fourteen subjects with DSM-IV social phobia were recruited. Fourteen healthy subjects aged and sex matched constituted the control group. We looked at two main factors in the eye tracking process: the number of fixations and the dwell time in the eyes area on the pictures.

Results: The main findings of this research are: confirming a significantly lower amount of fixations and dwell time in social phobic patients compared to normal subjects as a general mean; confirming a significantly lower amount of fixations and dwell time in social phobic patients compared to normal subject for the six basic emotions independently from gender; observing a potentially significant correlation between the severity of the phobia and the degree of gaze avoidance. However, no difference in gaze avoidance according to subject/picture gender matching was observed.

Conclusion: New techniques of desensitization, based on cognitive-behavioral principles and/or virtual reality systems, could be developed based on this paradigm of gaze avoidance and anxiety. We think that these works on gaze avoidance in social phobia can lead to define more clearly sub-types of the disorder (with or without gaze phobia) or to know if gaze phobia can be considered, in an ethological and evolutionist perspective, as the central nucleus of social anxiety. Objective: This study aimed at determining the functional neuroanatomy of mental pain, a hitherto neglected symptom in the study of depression, which according to DSM-IV is strongly linked with suicide.

Method: Mental pain (measured with the OMMP), suicidal ideation (measured using HAMD), hopelessness (measured using Beck's hopelessness scale), and regional cerebral blood flow as measured with SPECT were assessed in 39 depressed individuals.

Results: Levels of mental pain were significantly and positively associated with suicidal ideation and levels of hopelessness, and with blood flow in the occipitotemporal cortex, and in the dorsolateral and inferior frontal prefrontal cortex. Levels of mental pain correlated negatively with blood flow at the medulla.

Conclusions: The findings indicate that mental pain in depressed patients is associated with an increased risk of suicide.

The functional neuroanatomical findings suggest that mental pain is the consequence of deficient pain regulation including a deficient cognitive control, due to which depressed patients may not be able to get the pain out of their minds and perceive the pain to be without end. Further study of biological correlates is needed in order to test the hypothesis that both serotonergic and noradrenergic neurotransmission systems are involved in the development of mental pain in a similar way as is the case in physical pain. Introduction: Suicidal behaviour and impulsive aggressive behaviour towards others probably share a dysfunction in the brain serotonergic system. Irritability, hostility or assaultiveness may be associated with this dysfunction. A serotonergic dysfunction in the brain circuitry involved in the perception and regulation of emotion, can thus be hypothesized.

Aim: The aim of this study was to investigate if serotonergic abnormalities can be demonstrated in brain regions involved in the perception of emotion in impulsive aggressive and suicidal patients.

Patients and Methods: We studied the binding index of serotonin (5-HT2A) receptors in relevant brain regions of recent suicide attempters and recent violent offenders and compared these to normal controls. Depression, impulsiveness, anger and aggression were assessed using self-report questionnaires.

Results: Forty-two individuals participated in the study, including 22 healthy volunteers and 20 patients, of whom 10 patients were included following a suicide attempt while 10 patients were included following an impulsive aggressive act towards others. When compared to normal controls, the total patient sample was characterised by elevated levels of indirect aggression, trait and state anger and anxiety. The 5-HT2A receptor binding was increased in lateral and medial prefrontal cortex right-sided, in left inferior prefrontal cortex, in the left medial temporal region, in basal ganglia bilaterally and in the anterior cingulated gyrus, in comparison with normal data. When comparing patient subgroups, aggressive patients were characterised by higher receptor binding in right prefrontal lateral region.

Conclusion: Indications of a disturbed serotonergic function were found in brain regions which are involved in the perception and subsequent regulation of emotion. Dysfunctional emotion processing might be a serotonin-mediated commonality predisposing to suicidal or aggressive behaviour. During the last years, several studies have demonstrated that electroencephalogram (EEG) rhythms are modulated during cognitive processing. Those results have allowed proposing that simultaneous theta-(3-7 Hz), alpha- (8) (9) (10) (11) (12) (13) (14) , beta-(14-30 Hz) and gamma-(30-70 Hz) frequency band oscillations are required for unified cognitive operations. Specifically, alpha-amplitude modulations have been recently associated to attentional processes and consciousness. Despite those evidences, the temporal relation of EEG oscillations with attention mechanisms has not been well studied. Moreover, although it has been reported that spontaneous alpha oscillations are associated to the parieto-occipital cortex, it remains unknown which areas are associated to the attention-dependent alpha activity. We present the results of an EEG study where human subjects had to perform a spatial attention task. This task has demonstrated its ability to reflect the attentional modulation on the activation of early visual areas such as V1, V2, V3 and V4. Specifically, checkerboards are presented either to the left or to the right visual hemi-field while the attention is directed either to the right or to the left. Subject's task is to detect a very small change in the color of the checkerboard in the attended hemi-field. Analysis of the data includes spectral analysis using Morlet wavelets in order to determine both the evoked and the induced oscillations involved in the process.

Afterwards, we reconstruct the anatomical sources which generated those rhythms using the novel source reconstruction technique Swloreta in the frequency domain. This technique allows us to map the parametric increase in a given frequency band oscillation to the anatomical magnetic resonance (MR) images of the brain. We show the theoretical considerations which should be taken into account by researchers when performing this kind of experiments and we present a set of results obtained by us. Introduction: Previous morphometric magnetic resonance imaging (MRI) studies used the region-of-interest (ROI) analyses and revealed multifarious structural differences within subgroups of depressive patients compared to healthy controls, e.g. in the orbitofrontal cortex (Lacerda et al., 2004) , the anterior cingulate cortex (ACC) (Ballmaier et al., 2004) and the hippocampus (Sheline et al., 2003) . However, ROI analyses crucially rely on a priori defined regions and manual outlining or other stereotaxic methods to obtain volumetric measurements. At present, very few voxel-based morphometry (VBM) (Ashburner and Friston, 2000) studies in patients with major depression (MDD) investigated the relationship between cortical volume alterations and performance across multiple cognitive and psychopathological domains.

Aim: Our aim was to investigate the relationship between affective symptoms, cognitive deficits and structural abnormalities in patients with MDD. We presumed that grey matter (GM) abnormalities in MDD detected by VBM would involve areas functionally subserving working memory and executive functions, correlating with the occurrence of depressive symptoms in frontal cortical key regions that are known for being involved in both affective and cognitive processing.

Patients and Methods: By means of VBM and a standardized neuropsychological test battery consisted of 8 tests which assess alertness, divided attention, verbal and spatial working memory, executive function and inhibition processes, we examined 15 patients meeting DSM-IV criteria for MDD and 14 healthy controls. Psychopathology was rated by means of the Brief Psychiatric Rating Scale, the 21-item Hamilton Depression Scale, Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression Scale.

Results: Patients with depression showed reduced grey matter concentration (GMC) in the left inferior temporal cortex (BA 20), the right orbitofrontal (BA 11) and dorsolateral prefrontal cortex (BA 46) and in the bilateral cerebellum. Reduced grey matter volume (GMV) was found in the left hippocampal gyrus, the cingulate gyrus (BA 24/32), the thalamus and the left cerebellum. Structurecognition regression analyses revealed that decreased GMC of the right medial and inferior frontal gyrus was associated with both depressive psychopathology and worse executive performance as measured by the Wisconsin Card Sorting Test (WCST). Furthermore, depressive psychopathology and worse performance during the WCST were associated with decreased GMV of the hippocampal gyrus and the left cerebellum. Decreased GMV of the cingulate gyrus was associated with worse executive performance.

Conclusion: Our results provide evidence for regionally-specific alterations of grey matter in MDD patients. Grey matter abnormalities in the inferior temporal cortex, the orbitofrontal cortex and the cerebellum as well as in the cingulate gyrus, the left hippocampal gyrus and the cerebellum predicted impaired executive function in the patients with depression, indicating that selective grey matter alterations might at least partly account for manifest cognitive deficits observed in this disorder. Moreover, we demonstrated an overlap between key regions involved in MDD, psychopathology and cognitive deficits, suggesting that both symptom domains are associated with volume alterations in distinct areas of the frontal cortex. The time course of these abnormalities has yet to be elucidated by further research. Objective: The purpose of the study was to investigate the neural substrate that characterize resistant depressed patients using a new technique of non invasive IRM perfusion when compared to healthy volunteers.

Methods: A consecutive series of 6 patients and 6 matched controls were included. The group of chronic depressed patients answered strict criteria of inclusion in particular in the field of resistance to the treatment. They have a chronic depressive episode (HDRS>15) evolving for at least two years. The innovating imagery technique is the Arterial Spin Labeling (ASL): it allows to outpass the limitations of other techniques of functional neuroimagery since it directly reflects what happens in a basic state, without irradiation and injection of exogenic contrast products. To our knowledge, this is the first ASL study applied to psychiatry and to this population of patients.

Results: Statistic analysis underlined several cerebral hyperperfusion among resistant depressed patients in comparison to the healthy volunteers. We found a statistically significant (p=0.001) bilateral hyperperfusion of the Cg25 (subgenual cingulair 25) area, which is in accordance with Mayberg previous findings (Mayberg et al, 2005) . Other significant hyperperfusion areas also appeared: the left dorso-median prefrontal cortex (BA10), the left anterior cingular area (BA32) and left subcortical areas (putamen, pallidum, amygdala).

Conclusions: This preliminary study contributes to formulate the hypothesis that the Cg25 area is involved in the resistance to the treatment in depression. Other patients have to be included to confirm this results. ASL imagery technique appears to be an appropriate method for investigating functional abnormalities in psychiatric disorders. (Premack and Woodruff 1978) . Recently, neural correlates of mentalizing have been investigated by means of the classical Prisoners' Dilemma Game (PDG). Therefore, participants were scanned using fMRI while playing against alleged human or computer opponents (Kircher et al. submitted, Krach et al. submitted, Rilling et al. 2004 ). The results show that subjects attribute greater intentions and thoughts to a human opponent rather than to a computer implicated by stronger activations of the medial prefrontal cortex (mPFC). However, what exactly manifests the observed differences in mentalizing and their neural correlates remains unclear. We hypothesise that the degree of anthropomorphism and embodiment of the game partner will modulate cortical activity in previously detected ToM networks as the mPFC/ACC. Here we present the results of an fMRI study where participants had to play a classical PDG against four opponents with a stepwise increase in anthropomorphism and embodiment: a laptop computer partner (CP), a functional robot designed with two Lego Mindstorm sets (FR), the anthropomorphic robot BARTHOC Jr. (AR) and a human partner (HP). The results document a widespread overlap of activation in the mPFC irrespective of the partner being played. Directly contrasting the conditions revealed a significantly stronger signal change during the humanhuman interaction opposed to all other game partners. However, both types of robots elicited stronger activity in the medial frontal cortex than the computer partner. In conclusion, the present study is the first to apply functional neuroimaging methods to study human-robot interaction on a higher cognitive level such as ToM. The results of our studies are expected to have a severe impact on the design of social robots and the understanding of the functioning of ToM. Specifically in the group of autistic patients -characterized by an impaired ToM ability on humans, but exhibit a preference of robotic compared to human partners in an initial interaction (Dautenhahn et al. 2002 ) -the question of whether mentalizing might be facilitated when engaging with robotic agents is of major interest for psychiatry research. Introduction: Binding is essential for associating parsed information into coherent representations. Troubles of such a process could lead to deleterious combinations or thought disorganization in schizophrenia. It has been demonstrated that binding is disturbed in episodic memory (Danion et al., 1999; Luck et al., submitted) , due to prefrontal and hippocampal dysfunctions (Lepage et al., 2006) . However, little is actually known about binding in working memory and its pathophysiological basis. Aim: We used an event-related functional magnetic resonance imaging (fMRI) approach to study the neural basis of the binding process in a working memory task.

Patients and Methods: Sixteen patients with schizophrenia and 17 healthy controls were scanned during encoding, maintenance and recognition of verbal and spatial items. Three letters and three spatial locations were presented either bound (letters and locations were conjoined) or separate (letters were dissociated from locations). Thus, binding was assessed by subtracting the later condition to the former.

Results: The fMRI results showed that the two groups differed essentially for the maintenance of bound items. No main group differences were established for encoding and retrieval phases. The comparison between bound items and separate items maintenance revealed bilaterally hypoactivity in medial temporal structures (i.e. hippocampus and parahippocampal cortex) in patients relative to controls. However, the behavioural expression of these hypoactivities was quite modest. Patients showed more pronounced difficulties than controls for recognizing familiar bound items relative to familiar separate items, but they did not exhibit a specific deficit for bound items.

Conclusion: This fRMI study implicates the medial temporal structures as the pathophysiological basis of associative short term maintenance in schizophrenia. The disconnectivity hypothesis proposes that schizophrenia results from poor anatomical connections. Theoretically, its functional counterpart should be disintegration. Integration is thought to allow segregated neurons to interact as a coherent whole. This can be assessed by functional connectivity between pairs of regions. But new algorithms also allow to assess integration at the whole brain level. Areas of coherent activity form an integrated ''core''. The noninteracting part is referred to as the ''rest''. We used two fMRI studies of 13 stabilized medicated schizophrenic subjects compared to 11 matched controls. Subjects performed a lexical decision task in the first part and retrieval task in the second. Then we select a completely different imaging modality to study 6 patients and 6 matched controls with MEG. Participants were required to perform a verb generation task on semantic indices. Cores did not differ from the rests, neither in terms of anatomical distribution nor of functional integration. However, the cores were badly isolated from the rests and the rests were overly integrated in schizophrenic subjects. Furthermore, within the cores, anterior-posterior correlations were defective in patients (e.g. between the frontal and the parietal cortices) whereas frontal left-right correlations were excessive. Correlation was absent when considering medication but was significant for negative symptoms. Results were replicated in both fMRI studies and in the MEG study. Thus, it appears that schizophrenia entails a deleterious combination of too much ''noisy'' integration (into the rest) but also too little ''significant'' integration (defective anterior-posterior functional connectivity).

Which integration disorder is primary, which is secondary?

The different physiopathological hypothesis What should be the next move Background: The serotonin-1A (5HT1 A ) receptor system has been implicated in the physiopathology of major depression as showed by post-mortem studies of suicide victims and depressed subjects dying of natural causes. Neuroimaging (PET) using [11C]WAY-100635 high lightened lowered 5HT1 A receptors in unmedicated patients with acute major depression. The interest of 29-methoxyphenyl-(N-29-pyridinyl)-p-18F-fluoro-benzamido-ethylpiperazine (18F-MPPF), a newer 5HT1 A antagonist, which has a similar affinity to serotonin for 5HT1 A receptors (conversely to WAY-100635 usually used), has been proven in different pathological conditions, in animals and humans. The aim of this study is to explore the binding potential (BP) of 5-HT1 A by the 18F-MPPF in unmedicated subjects with severe acute depression. Material and Methods: 6 patients were included (5 women, 1 man, mean age 59 y.o.), meeting DSM IV criteria for major depressive episode (MADRS score > 40, either depressive or bipolar disorder). Wash-out for any serotoninergic medication was realized previously neuroimaging exam (18F-MPPF-PET scan and 3 Tesla MRI). PET scan was realized 1 day before electroconvulsivetherapy (ECT)'s beginning. Patients have been compared to 14 age and sex matched healthy volunteers. The resulting parametric voxel-by-voxel BP maps were analyzed by voxel-based statistical parametric analysis with SPM2.

Results: Relative to healthy control group, depressive patients' group showed a significantly decreased BP in the bilateral parahippocampal gyri extended to mesio-temporal cortex (Z=5.81, p<0,001, k=7250, coordinates in MNI/ICBM )28/)30/)16 and Z=5.54, p<0,001, k=6078, coordinates 30/)26/)18), the cingulate (Z=5,17, p<0,001, k=7545, 4/40/0) and a significantly increased BP in cerebellum (Z=5.30, p<0,001, k=1101, coordinates )12/)56/)28).

Conclusion: As far as we know, this is the first study exploring the 5HT1 A receptor function in the depression with the 18F-MPPF PET radiotracer. The significant decrease of the binding potential in the limbic system fund is coherent with the literature and confirms the prominent role of this receptor in the physiopathology of major depression. Larger extent difference in activations seen with MPPF versus WAY-100635 method may reflect the advantage of the first radiotracer in depression studies. Depression is a common condition among elderly people.

Objective: Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for 36-week treatment of elderly adults with recurrent major depressive disorder and dysthymia diagnosis. We aimed to investigate the association between depressive symptoms in treatment with antidepressant drug and various sexual functions in late life.

Method: A sample (31 patients) was recruited for treatment with duloxetine, 60 mg/day for 36 weeks with DSM-IV-diagnosed depressive disorder and dysthymia with anxiety symptoms. The measures included the Geriatric Depression Scale, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Sexual Function Questionnaire Version 2 (SFQ-V2) and standard safety and tolerability assessments.

Results: Patients had a median age of 69 years. Duloxetine treatment showed significantly greater baseline-to-endpoint reductions in Hamilton depression scale ()5.23 versus ) 1.42 ), Hamilton anxiety scale ()6.14 versus )1.09), ()6.33 versus ) 1.10) , and Geriatric Depression Scale ()5.08 versus )1.12) total score. Hamilton depression scale response (87.3% on sample) and remission (72.% on sample). At the Sexual Function Questionnaire Version 2 (SFQ-V2) score there were not difference. Duloxetine significantly improved Hamilton Anxiety Rating Scale for anxiety and Geriatric Depression Scale and Hamilton Depression Rating Scale for depression.

Conclusions: Duloxetine improved depression and anxiety and was safe and well tolerated in elderly patients with recurrent major depressive disorder and dysthymia. In the patients in treatment with duloxetine for all domains of sexual functions there were not differences. Introduction: Practice guidelines recommend maintaining antidepressant treatment for a long period of time, particularly in elderly patients. Little is known about differences across the newer prod-ucts concerning non-persistence and related health care costs in this population.

Aims: To compare, in a real-life setting, the newer antidepressants with respect to non-persistence, health care costs and cost/ persistence ratio in the community-dwelling elderly.

Patients and Methods: An observational retrospective cohort study was conducted in the community-based elderly outpatient members of the general drug program of Quebec. 12,825 outpatients age 65 years and older who initiated an antidepressant treatment in 2000 were followed-up over 12 months. Non-persistence was defined as treatment duration of less than 180 days. Economic variables included direct health care costs assessed through Quebec administrative health databases. Cost/persistence ratio and incremental cost/persistence ratio were obtained for each product; persistence being a measure of effectiveness. Product comparisons were adjusted for patient characteristics, medical history, and physician specialty.

Results: 55,6% of antidepressant treatments were deemed nonpersistent. Products associated with low antidepressants costs were often associated with high costs of other medications and health care services, and vice versa. Paroxetine was associated with the lowest non-persistence (50,5%; 95%CI 48,5-52,5) and one of the most favourable cost/persistence ratios (4,869 CDN$ per persistent treatment). Trazodone had the highest non-persistence (65%; 95%CI 63-67) and one of the highest cost/persistence ratio (6,251 CDN$ per effective treatment). Fluoxetine was associated with the most favourable incremental cost/persistence ratio.

Conclusion: Non-persistence to antidepressant treatment is very frequent in the elderly population of Quebec. Intervention programs aimed at decreasing non-persistence would optimize the use of health care resources and result in economic advantages. Introduction: Catatonia is nowadays defined as a neuropsychiatric disorder characterized by motor, affective and behavioral disorders. Once associated to schizophrenia, it is now mainly considered as a transnosographic disorder, in which the symptomatology shares similarities with Alzheimer disease (AD).

The risk of misdiagnose catatonia in the elderly as an advanced state of dementia has been underlined in the literature. Since the prognosis of those diseases is very different, and since efficient treatments for catatonia, such as lorazepam, are well-documented, an accurate diagnosis is mandatory.

Aim: A one-year prospective study was conducted in our department in order to evaluate the prevalence of catatonia among patients admitted with AD.

Patients and Methods: During one year, (from May 2006 to April 2007), all patients admitted in our geriatric psychiatry unit who met the DSM IV TR criteria for AD underwent a neuropsychological battery (MMS, Dementia rating scale, evaluation of the executive function) and a clinical evaluation for a catatonic disorder. If catatonia was suspected, a lorazepam test was performed to ascertain the diagnosis. Catatonic patients were evaluated before and after the lorazepam test with the following: the Rosebush scale, the Northoff catatonia scale and the Bush and Francis catatonia rating scale.

Results: 118 patients met the diagnosis of AD. Among them, 18 patients were diagnosed as catatonic i.e. 15.25%. For those 18 patients, the entire symptomatology that shared some similarities with dementia disappeared with appropriate treatment. Results to catatonia scales and to MMS confirm the improvement.

Conclusion: This study confirms that a significant number of catatonic patients (15%) can be diagnosed among patients consid-ered as AD. Their symptoms are reversed by lorazepam. If these results are confirmed by further studies, and because of the continuous growth of the elderly population, this study may have an interest in terms of public health. Introduction: Catatonia was first described by Kahlbaum in 1874. This neuropsychiatric disorder, now considered as a common and transnosographic syndrome, is characterized by the occurrence of concomitant affective, motor and behavioral symptoms. The recent literature shows that catatonia is particularly common in the elderly. Often misdiagnosed because of the diversity of the clinical features, catatonia is easily mistaken with dementia.

Since lethal evolutions have been described (especially with neuroleptics, usually prescribed for behavioral disorders in patients with dementia), it appears essential to diagnose positively and quickly catatonia.

Aim: The treatment of catatonia is mainly based on electroconvulsivotherapy (ECT) and, or lorazepam. Appropriate lorazepam posology is still indeterminate despite its crucial importance. If lorazepam is prescribed with improper posology, either too low or too high, diagnosis may be erroneously rejected. Beside, in case of misdiagnosis, lorazepam and ECT are not effective for dementia. It is then essential to diagnose catatonia. This is why we report here a pharmacological tool for diagnosis confirmation.

Patients and Methods: When clinical diagnosis of catatonia is suggested, and if there is no contra-indication for benzodiazepines, 1mg of lorazepam is orally given after a clinical and psychometrical evaluation. If no change is observed after 1 hour, 1 additional mg is given and the patient is reevaluated and so on. If symptoms disappear (and this, in a spectacular way), the administration of lorazepam is stopped, the test is considered as positive and diagnosis of catatonia is confirmed. Further daily treatment will be based on the amount of lorazepam received during the test.

Results: During one year, this sequential administration of lorazepam was tested on 28 consecutive patients for whom catatonia was suspected. The test turned positive in all cases.

22 were more than 65 years-old (average 73, sex ratio: 4 male, 18 female). These data corroborate the literature about the prevalence of catatonia in the elderly.

Conclusion: The standardization of lorazepam administration described herein constitutes a diagnostic and therapeutic tool which can be of a great interest for the management of catatonia in the elderly. Background: Metabolic as well as psychiatric disorders are an important issue pertaining to the current scientific interest in unhealthy aging as several studies have shown a comorbidity between depression and metabolic syndrome. The hypothalamuspituitary-adrenocortical (HPA) axis and the central serotonin neurotransmitter system have been suggested to be involved in both diseases. Therefore we investigated, whether genetic variants in genes regulating HPA and central serotonin systems may contribute to the prevalence of metabolic syndrome in depressed patients.

Methods: The sample for unipolar recurrent depression consisted of 1000 patients and 1000 psychiatric healthy controls of Caucasian origin. All subjects were diagnosed by trained psychiatrists according to the DSM IV criteria. Prevalence of the metabolic syndrome was defined according to the IDF and ATP III criteria. 484 Single Nucleotide Polymorphisms (SNPs) in 36 genes were genotyped in an exploration sample of 347 patients and 350 controls respectively. Significant associations after correction for multiple testing were investigated in the replication sample consisting of the remaining 641 patients and 650 controls.

Results: We found a significantly higher prevalence of the metabolic syndrome and metabolic disorders in both male and female patients with unipolar recurrent depression compared to healthy controls, with the highest prevalence among female patients. In the exploration sample two SNPs located in the TPH2 gene showed significant associations (p<0.0001) with the prevalence of the metabolic syndrome in depressed patients after correction for age, gender and multiple testing. The results are in concordance with a dominant-recessive genetic mode of inheritance. One of these associations could be replicated in the larger sample (p<0.05).

Conclusions: These findings indicate variants in the TPH2 gene to be associated with the prevalence of metabolic syndrome in depressed individuals. No associations with depression susceptibility could be detected in our study. We suggest that TPH2 is involved in the mechanisms of metabolic disturbances in unipolar recurrent depression, rather than in the development of the disease. Introduction: An increase of reactive oxygen species (ROS) in the blood of schizophrenic patients is found in some studies. The enhancement of ROS via augmentation of NADPH-oxidase activity, could be causative for side effects like blood dyscrasia.

Aim: In this study the effects of typical and atypical antipsychotics on leukocyte ROS formation were tested.

Methods: Leukocytes (100.000 cells) from volunteers (n=10) were incubated after apharesis with haloperidol, clozapine and olanzapine (25 lg/ml) for 30 min. The content of ROS was detected in the presence of 0.8 mM 1-hydroxy-3-carboxymethoxycarbonyl-2,2,5,5-tetramethylpyrolidine (CMH) and 0.05 mM deferoxamine, a ROS scavenger. For analyzing the ROS formation an electron spin resonance spectroscope was used. NADPH-oxidase activity was analyzed by using lucigenine, the chemoluminiscence detection was carried out using a microplate luminometer.

Results: Under all treatment conditions, the ROS and NADPHoxidase activity were significantly increased. The largest effects were obtained each with clozapine as compared to haloperidol and olanzapine.

Conclusion: This study shows that different antipsychotics exert an increase of ROS in human leucocytes. In both treatment procedures clozapine was the strongest inductor of ROS formation, which could be crucial for blood dyscrasia. Introduction: Clinical, epidemiological and immunological studies have implicated an association of inflammatory processes and the pathogenesis the affective and schizophrenic spectrum disorders. Evidence comes from genetics, histopathology, imaging, CSF and blood abnormalities, CSF cytokines, IL-6, cytokine modulating drugs, and cell mediated immunity.

Aim: We addressed the question of immune inflammatory parameters in major psychoses with advanced CSF analytical methods in cooperation with experienced research and routine CSF laboratories. Improved test sensitivity and enhanced, integrated and evidence based methods of laboratory result interpretation were applied 1 .

Patients and Methods: Sixty three patients (29 female and 34 male) diagnosed with major psychosis (24 patients with affective spectrum and 39 with schizophrenic disorder) hospitalized during 2001 and 2006 after experience of multiple therapeutic approaches without long lasting improvement were included. Mean age at study entry was 37.4 years, mean duration of illness 9.4 years.

Patients underwent lumbal puncture and simultaneously peripheral blood (PB) was taken for investigation of agent specific antibody index (AI), blood CSF barrier (BCB), intrathecal immunoglobulin production, oligoclonal bands (OCB) and ANA/APA.

Results: OCB in the CSF but not in PB were observed in 4 (6.3%) patients, simultaneously in PB and CSF in 5 (7.9%) patients. CSF total cell count was > 5/lL in 5 (7.9%) of the patients. One patient displayed an increased agent specific AI for Borna disease virus and two (3.6%) for ANA/APA. BCB was impaired in 21 (33.3%) patients. Any abnormalities of AI, OCB in the CSF only, ratio immunoglobulin PB/CSF (QIgG, QIgA, QIgM) were observed in 9 (14.2%) patients. Any signs, as assessed by PB or CSF immunochemistry of systemic inflammation, CSF inflammation, BCB impairment were diagnosed in 35 (55.5%) of all patients (66.6 % of affective and 48.7% of schizophrenic patients).

Conclusion: Systematic screening of patients with major psychoses for signs of inflammation by sophisticated methods for CSF and CNS investigation reveal in a majority of the patients inflammatory processes which may guide therapeutic approaches in future. Introduction: There is increasing evidence that inflammatory mechanisms contribute to the pathogenesis of major psychiatric disorders (MPD). The specific nature of the inflammatory abnormalities remains to be elucidated, though providing yet a basis for therapy trials 1 .

Aim: In this study assess lymphocyte activation and T regulatory cells (Tregs) cell surface markers in patients with psychiatric disorders and subgroups of patients with neurological disorders in paired samples of CSF and blood (PB) to evaluate aberrations in the immunosurveillance. We used modern flow cytometers which allows with high sensitivity to detect up to eight parameters per cell.

Patients and Methods: CSF and PBMC were collected simultaneously from 45 patients, 17 patients with major psychoses (MPD), 16 with non-inflammatory neurological diseases (NIND), 7 with meningitis (MEN) and 5 with chronic inflammatory diseases (CIND).

Peripheral Blood Mononuclear Cells (PBMC) were isolated by Ficoll, CSF-cells were centrifuged. Samples were stained with monoclonal antibodies directed against CD4, CD8, CD25, CD45, CD69, CD127 (BD and Caltag-Invitrogen). Stained cell samples were analysed using BD FACSAriaä cytometer and BD FACSDiva software.

Results: Significant differences (p<0.05) were observed in PB for CD4+ cells (MEN: 45.8% versus NIND: 33.06% / CIND: 31.03%); in PB for CD4+CD45RO+ cells (MEN: 24.08% versus CIND: 11.12%); in PB for CD4+CD25+ (MEN:0.89% versus CIND: 0.28% / MPD: 0.39%); and in CSF for CD4+CD127 dim cells (MEN: 5.15% versus MPD: 10.18%). A significantly higher frequency of CD4+CD25+CD127dim, representing T regs were observed in PB of MEN (0.25%) versus CIND (0.09%). Cluster analysis revealed 6 out of 17 MPD displaying a ratio of CD4+/CD8+ cells in PB >3.2, but only 2 NIND patients. Another cluster of patients with T regs in CSF >10% and in PB < 15% included 7/17 MPD versus 2 NIND patients.

Conclusion: In summary, multiparameter FACS analysis of CSF versus PB is feasible and distinct patterns of T cell subsets were identified in both neurological and psychiatric disorders. Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. There are few trials supporting the efficacy of antidepressants in bipolar disorder, and some evidence that they may induce rapid cycling, switching and mania.

Objective: Determine the efficacy and tolerability of olanzapine/ duloxetine combination (ODC) for treatment of acute bipolar I depression.

Method: The 24-week, acute phase this study ODC has evaluated the Combination (20/120 mg/day; N = 29) in patients with DSM-IVdiagnosed bipolar I disorder, depressed.

Results: ODC-treated patients had significantly improvement in change from baseline across the 4-week and 6-week and 12-week and 24-week treatment period on the Clinical Global Impressions-Severity of Illness scale (baseline vs endpoint) (p = .001), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .001), Hamilton Depression Rating Scale (HAMD) (p = .002) and Young Mania Rating Scale total scores (p = .002). Response rates did significantly differ between groups (Females vs Males) when defined as > or = 50% reduction in MADRS and HAMD score (Females, 74.2% vs Males, 69.2%; p = .022).Time to response was significantly shorter for ODC-treated patients Females group (median days [96% CI] =Females, 12 [9 to 17] vs. Males, 18 [16 to 29]; p = .001). There was not significant incidence of adverse events.

Conclusions: Patients with acute bipolar I depression in combination treatment (Olanzapine/Duloxetine) had statistically significantly improvement in depressive and manic symptoms. Increased dose duloxetine to 120 mg /day did not induce mania or hypomania or manic symptoms. Differential response to ODC combination in group Males was associated with reduction treatment dose duloxetine to 60 mg/day in five patients males for nausea presence. Introduction: High prevalence of sleep disturbances and particularly their chronic course are today a recognized medical and socioeconomic problem. A survey study of the sleep behavior of the Swiss population was therefore performed with the aim to provide a background for estimating the need for specific programs that would improve its diagnostics and the treatment.

Method: A specifically constructed questionnaire (80 items) was addressed (telephone interview, computerized CATI system) to a random sample of subjects of both sexes, located in main language regions of Switzerland. For data analysis the recorded responses were transformed into numerical and categorical values according to the DSM-IV criteria and definitions of insomnia.

Results: The analyzed sample consisted of a total of 1002 subjects (men and women, mean age 39. 5 ± 15.18 ) from all language Swiss regions and all professional and occupational categories. Insomnia, (according to DSM-IV, median n symptoms =6) was present in 31.3% of subjects and was slightly more frequent in females. The most frequently affected were the clerks/employees (>30%), retired (48%) and widowed (>65%) and the most severe forms were highly prevalent in jobless or without occupation subjects. Day-time consequences of insomnia were severity-related, marked and numerous. They affected between 25 (mild insomnia) -100% (severe insomnia) of subjects. They included impairments of professional activity, mood, physical and mental health. Unsatisfactory quality of life (>70%), sexual problems and impaired social life were common.

Conclusion: The results of this survey show that insomnia, corresponding to stringent diagnostic definitions, has rather high prevalence in the Swiss population. Particularly in view of marked day-time consequences insomnia is therefore a medical and socioeconomic problem, which needs attention in the practice. Aim: To evaluate the efficacy, safety and tolerability of aripiprazole monotherapy as acute and continuation therapy for acute bipolar I mania.

Patients and Methods: Patients with acute bipolar I mania (Young mania rating scale [YMRS] Total ‡20), manic or mixed, who required hospitalization were randomized (1:1:1) to double-blind aripiprazole (15 or 30 mg/day; n=167), placebo (n=153) or haloperidol (5-15 mg/day; n=165) for 3 weeks. Aripiprazole and haloperidol patients remained on blinded treatment for a further 9 weeks. Outcome measures included: mean change from baseline in YMRS Total score at Week 3 (primary endpoint) and Week 12; mean change from baseline in Clinical Global Impressions Bipolar Version-Severity of Illness (CGI-BP-S) (mania) score; response rate ( ‡50% improvement from baseline in YMRS Total); and remission rate (YMRS Total £12).

Results: Mean change from baseline to Week 3 (LOCF) in YMRS Total score was significantly greater with aripiprazole ()12.0; p=0.039) and haloperidol ()12.8; p=0.005) versus placebo ()9.7). Improvements were maintained to Week 12 for aripiprazole ()17.2) and haloperidol ()17.8; LOCF). Improvements in mean CGI-BP-S (mania) scores from baseline were significantly greater with aripiprazole () 1.4; p=0.044 ) and haloperidol () 1.6 ; p=0.004) versus placebo () 1.2 ; LOCF) at Week 3, increasing at Week 12 with both aripiprazole ()2.1) and haloperidol () 2.2) . Response rates at Week 3 were numerically greater with aripiprazole (47.0%; p=0.145) and haloperidol (49.7%; p=0.069) versus placebo (38.2%; LOCF), increasing at Week 12 with both aripiprazole (72.3%) and haloperidol (73.9%). A similar pattern was observed for remission rates. Aripiprazole was well tolerated.

Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (53.3% vs. 24.0%). At Week 12, clinically-relevant weight gain was reported in 5.1% and 5.8% of aripiprazole and haloperidol patients, respectively (p=0.723; LOCF). Fewer patients experienced potentially clinically-relevant changes in prolactin levels with aripiprazole (22.4%) versus haloperidol (66.2%) at Week 12.

Conclusions: Aripiprazole significantly improved symptoms in acutely manic patients after three weeks. Clinical improvements with aripiprazole were sustained to Week 12 and were similar to haloperidol. Aripiprazole was generally well tolerated. Introduction: In clinical practice, mood stabilizers in combination with antipsychotics are widely used for the treatment of bipolar disorder; however, in some studies, atypical antipsychotics as adjunctive therapy have failed to separate from placebo in efficacy endpoints.

Aim: This multicentre, randomized study aimed to evaluate the efficacy and safety of adjunctive aripiprazole in the treatment of patients with bipolar I mania (manic/mixed) partially nonresponsive to lithium or valproate monotherapy.

Patients and Methods: Following screening, psychotropic washout and attainment of therapeutic levels of lithium (0.6-1.0 mmol/l) or valproate (50-125 lg/ml) (Phase 1), patients received open-label lithium or valproate monotherapy for 2 weeks (Phase 2). Partial non-responders (Young Mania Rating Scale [YMRS] Total score ‡16 during Phase 1 and at the end of Phase 2, where any decrease between Phase 1 and 2 had to be £25%) were randomized (2:1) to double-blind adjunctive aripiprazole (15-30 mg/day; n=253) or placebo (n=131) for 6 weeks. Primary endpoint was mean change in YMRS Total score from baseline.

Results: Mean improvement from baseline in YMRS Total score at Week 6 (primary endpoint) was significantly greater with aripiprazole ()13.3±0.5 from 23. 1±0.3) versus placebo () 10.7±0.7 from 22.7±0.5; p=0.002 ; LOCF). Significant improvements in YMRS Total scores with aripiprazole versus placebo occurred from Week 1 onwards (p<0.05).

Improvement from baseline at Week 6 in Clinical Global Impressions Bipolar Version-Severity of Illness (mania) score was significantly greater with aripiprazole ()1.9±0.1 from 4.2±0.1) versus placebo () 1.6±0.1 from 4.1±0.1; p=0.014 ; LOCF). Remission rate (YMRS Total £12) was significantly greater with aripiprazole versus placebo as early as Week 1 (p=0.025), continuing to Week 6 (66.0 vs. 50.8%; p=0.004; LOCF). Response rate ( ‡50% improvement in YMRS Total) was also significantly greater with aripiprazole versus placebo at Week 6 (62 .8 vs. 48.5%; p=0.008 ; LOCF). Aripiprazole was well tolerated, with no significant between-treatment differences in clinically-relevant weight change from baseline at Week 6 (p=0.718; LOCF).

Conclusions: In patients partially non-responsive to lithium/ valproate monotherapy, adjunctive aripiprazole significantly improved mania symptoms versus lithium/valproate monotherapy as early as Week 1, with a tolerability profile similar to that of aripiprazole monotherapy studies. We handle only 4 dimensions and need models like Weygandt's T-A-M-model for ''bipolarity'' for understanding. Kathleen Askland 2006 proposed the bipolar spectrum to be due to the interaction of alterations of neurochemical capacity (!range) and neuroelectrical modulation (!tonicity) driven by genes for transmitter systems and ion-channels respectively. Using a 3Dmodel derived from Kraepelin (1913) it is argued that neurochemical capacity ''corresponds'' to the T-axis (representing 4-D-''Thought''-knowing that) and neuroelectrical modulation to the A-axis (summarizing higher-dimensional ''Action''-knowing how i.e. psychomotricity). 1 

At its corners Depression and Mania each have three mixed states with inverted values for T, A or M. It clarifies Kraepelin's cryptic illustration '' Fig.228'' showing two of six possible phaselagged T-A-M-sinus curves. These were borrowed from electrical RCL-circuits, which behave like spring-pendula. 2 . The cyclical T-A-M-model: a loop is inserted into the CUBE, which is made out of an approach wave closed to form a perception-action-cycle (quietness! need! appetitive planning ''Thought''! ecologic encounter by ''Action''! consumption!…). This cycle, when tilted, can generate the above sinus curves. It is attracted by the cubes corners (mixed states, anxiety disorders, basic emotions). 3 . The model predicts that psychomotoric systems (A) express ''tonicity'' and are more influenced by changing ion channels and vice versa that symbolic search systems (T) express ''range'' and are more influenced by changing main transmitters. Tonicity and range of ''Mood'' seem less illuminating. 4 . Deformed loops depict temperaments. Cholerics use quick frugal models (T) for ongoing affairs: their loop rapidly leads to ''Action'' or ANGER. As a spring-pendulum they have a weak ''T''-spring; sanguines with a stiff ''T''spring search for truthful, but too slow models. ANGER-FEAR (Lara 2006 ) is a skewed dimension in the T-A-plane. 5 . A graphical synopsis of these models and present evidence is shown. Friedel E., Schlagenhauf F., Park S.Y., Kahnt T., Wrase J., Ströhle A., Heinz A. Dept. of Psychiatry, Charité Hospital, Berlin, Germany Fear and anxiety depend on amygdala function. A functional polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with amygdala activation by emotionally salient faces, anxiety as well as mood disorder in healthy controls. Several studies showed that SCL6A4 genotype accounted for about 30% of the total variance in amygdala response during the presentation of aversive but not affectively positive visual stimuli, which were equally salient. S-allele carriers also showed stronger prefrontalamygdala connectivity.

This suggests that increased amygdala responses in s-allele carriers are related to altered serotonergic modulation of prefrontal afferents within the amygdala. In patients with major depression, amygdala activation to aversive stimuli and prefrontal connectivity may be dysfunctional. This was tested in 20 patients with major depression and 20 age-matched healthy controls. Results will be discussed with respect to genotype effects on limbic activation and connectivity. Objective: Worldwide, cancer is the second most frequent cause of death after the ischemic heart disease. Lifetime prevalence of psychiatric co-morbidities in cancer patients is 30-40%.

Major Depression is the most prevalent psychological disorder in patients with cancer. Major depression has a negative effect on quality of life, self-care, treatment compliance and treatment response. In our study, we evaluated the prevalence of major depression in patients with cancer and the related factors which might affect this co-morbidity.

Methods: Hundred patients with cancer (53 men and 47 women) who attended to oncology outpatient units were recruited to the study. Participants were assessed with ''Structured Clinical Interview for DSM-IV (SCID) -Mood Disorders Module'' and ''The Questionnaire for the Assessment of Patients with Cancer''.

Results: The prevalence of major depression in patients with cancer was 22%. The prevalence of major depression was higher in women than in men. Insomnia was found in 50% of the patients with cancer. Insomnia was recognized in 20% of patients with breast cancer and 15% of patients with lung cancer. Suicidal ideation was found in 11% of the patients with cancer. The prevalence of suicidal ideation increased with age and it decreased as the disease progressed.

Conclusion: Major depression is a frequent psychiatric problem in the patients diagnosed with cancer. By reason of frequency, early recognition of major depression and the related factors will provide appropriate psychiatric treatment. The frequency of suicidal ideation is even important in this population. Psychosocial support and psychiatric treatment approaches should be the focus of further attention in oncology clinics.

Introduction: Long has been interesting the fact whether the unipolar and bipolar patients show different level of cognitive function during periods of the exacerbation of disease (1) as is the case with the difference of the clinical profile of each of them (2). Additionally, lateralization potential has been compared in the two tested groups and in control group (3) .

Aim: The aim was the analysis within the scope of cognitive function and lateralization potential among the groups of patients with unipolar and bipolar affective disorder. In addition, a similar comparison has been carried out in the healthy control group.

Patients and Methods: The examination was carried out among 108 patients divided into three groups: D 1 -Unipolar, D 2 -Bipolar and K-Control. Persons from groups D 1 and D 2 were hospitalized due to low depression having similar exacerbation of disease in both groups. All the examined patients were right-handed which was confirmed by EHI (Edinburgh Handedness Inventory) and Gorynia & Dudeck tests. The RAVLT (Rey Auditory Verbal Learning Test), RCFT (Rey Complex Figure Test) and WCST (Wisconsin Card Sorting Test) tests were used during the examination. The lateralization index fixed based on the CV test (dichotic listening -consonant vowel). Results: HDRS: Similar level of depression in both groups: D 1 (23,3) vs. D 2 (21,7). RAVLT: Groups D 1 i D 2 function in a similar way, showing a small advantage of efficiency in group D 2. RCFT: Patients from group D 2 show better efficiency in spatial/visual memory in comparison with group D 1 . WCST: Better functioning of patients from group D 2 in comparison to group D 1 . CV: similar outcomes in groups D 1 and D 2, no differences. In comparison to the control group all the outcomes from groups D 1 and D 2 are clearly lower.

Conclusion: Repeatability of the outcomes in the three tests points at better cognitive functioning of the persons from Bipolar vs. Unipolar group. There are no differences in the lateralization potential in these groups. All the outcomes of the control group are much better than in the other two groups which confirms reliability of the carried out examination. Introduction: Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness and additional symptoms, such as cataplexy, hypnagogic hallucinations and sleep paralysis (1). Depressive symptoms are commonly reported in Narcolepsy (2) (3) .

Aim: To assess depressive symptoms in narcoleptic patients and controls and to compare depression scores of patients with (NC+) and without cataplexy (NC-).

Patients and Methods: Sixty-eight narcolepsy patients (33 NC+, 35 NC-) and age matched healthy control group (49 subjects) were seen for psychological testing. They completed Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (ZDS), Numeric Subjective Depression Scale (NDS), Profile of mood States (POMS) and Epworth Sleepiness Scale (ESS). The majority of patients were under pharmacological treatment.

Results: NC+ and NC-had significantly higher scores in BDI, ZDS and NDS than controls (Kruskal-Wallis, Chi 2 =11. 1, 15.8, 15.1, p < .01) . Between NC+ and NC-there was no significant difference. The percentage of depression (BDI >19 points) was 16.4% in narcolepsy vs.2% in controls, depressive symptoms (18-19 points) were 4.5 vs.0% and dysphoria (10-17 points) was 20.9% vs.14.3% (p=.01, Chi 2 =12.283). In NC+ and NC-the correlation (Pearson) between sleepiness (ESS) and depression (ZDS and BDI) was not significant. According to POMS, NC+ and NC-showed a much higher degree of impairment (p< .001) in all subscales compared with controls.

Conclusion: The narcolepsy patients are more depressed than controls, but for dysphoria the percentage is relatively similar. The lack of a significant difference between NC+ and NC-in the level of depression may indicate that the major psychosocial burden in narcolepsy is caused by the inevitable sleepiness, and not by cataplexy. Introduction: Sleep is critically involved in the consolidation of motor memory: It has been repeatedly shown that post-training improvements in several motor tasks strictly require a night of sleep.

Aim: We hypothesized that this kind of memory consolidation is strongly impaired in depressed older patients compared to depressed younger patients and healthy controls.

Patients and Methods: 12 young (22-30 years) and 23 older (32-64 years) medicated patients with an acute episode of major depression (HAMD>17), 35 healthy matched controls and 10 remitted patients (31-65 years, HAMD<8) were assessed using a sequential motor learning task: On the first day (between 0900 and 1200 h), subjects were required to repeatedly tap a sequence of 5 numbers during 12 periods of 30 sec, interrupted by a 20 sec pause each, as often and correctly as possible on a computer keyboard (training session).

Changes of motor performance were measured in a three periods test session 24 h later, after a night of sleep.

Results: In the older-age group the healthy controls showed a better overall performance than the acute patients and an 18% overnight increase in the number of correctly tapped sequences, whereas the patients showed a 12% overnight decrease (p<.01). In the young-age group, however, patients and controls showed almost the same motor performance and overnight increase (24% vs. 25%). Remitted patients and controls, too, did not differ significantly in their motor performance or overnight increase (14% vs. 18%), but remitted and acute patients in the older age group did (p<.01). There were no differences in training improvement between any of the groups.

Conclusion: Our results clearly show that age and an acute episode of major depression exert strong synergistic effects on sleep-dependent procedural learning: Overnight motor memory consolidation is not affected in young patients, but severely impaired in older patients with an acute episode of major depression. This impairment seems to recover after remission from depression. Introduction: During the 10 last years, more than 30 clinical trials assessed the therapeutic effect of repetitive Transcranial Magnetic Stimulation (r-TMS) in refractory depression, comparing r-TMS to placebo or to electroconvulsive therapy (ECT), but most of them were conducted with nonpsychotic major depression.

Aim: A 77 years old bipolar II woman was hospitalised in our Unit for a severe treatment-resistant depression with psychotic features (delusion, Cotard's syndrome). General anaesthesia needed for ECT was contraindicated. We decided to begin r-TMS sessions.

Material and Methods: 43 sessions of r-TMS (left dorsolateral prefrontal cortex, 90% Tm, 10 Hertz, 1600 stimulations/session) were administered. Antidepressant (moclobemide) and antipsychotic (olanzapine) remained unchanged during the hospitalization.

Results: The patient improved slowly during the two first weeks of r-TMS treatment. We then administered two sessions daily, and the patient dramatically improved. Delusional ideation totally disappeared. HAMD decreased from 32 to 12. BDI and CORE standardised assessments were also performed. No adverse affect of r-TMS was observed.

Conclusion: To our knowledge, there is no published case report about r-TMS and depression with psychotic features. After an individual benefit-risk clinical assessment, r-TMS may be considered as a possible second-line treatment strategy in some patients with psychotic major depression, when other treatment options (ECT, medications) are contraindicated, or are inefficient. Introduction and Aim: Biofeedback is an old recognized therapeutic method used in sleep and anxiety disorders but whose effects have been poorly objectively explored to date. The procedure that we wanted to test in this open, prospective, study includes five biofeedback sessions (with EMG, respiratory frequency, cardiac frequency and electrodermal activity monitoring), realized weekly after a first sequence of ten classical relaxation sessions.

Patients and Methods: One hundred and two patients with psychophysiologic insomnia, without significant psychiatric comorbidity, have been assessed before and after treatment through the Insomnia Severity Index (ISI) scale, anxiety and depression scales (HAD, BDI, STAI), somnolence scale (Epworth), morningness scale (Horne), and personality inventory (TCI-R). Our sample comprised a majority of women (70.6%), with a mean age of 47.5 ± 13.9 years.

Results: Post-treatment assessment showed a marked improvement of sleep disorders, with a significant decrease of ISI scores (19,0 vs 15,7; p<0,001). Moreover, a decrease of depressive (BDI, HAD-D) and anxiety (HAD-A) symptoms was also observed, despite relatively low initial scores. Pre-treatment insomnia scores were correlated with BDI scores (r=0.23; p=0.02), as well as with BMI (r=0.34; p=0.01). On the other hand, no significant correlation was observed between ISI scores and TCI-R personality dimensions. When compared to a 77-subjects normative sample, personality profiles of insomniac patients were distinguished by higher harm avoidance (HA) scores (p<0.001) and lower novelty seeking (NS) scores (p=0.02). Furthermore, patients with this more evident profile (high HA and low NS) seemed to be the best responders to biofeedback according to ISI scores decrease.

Conclusion: This study confirmed the efficacy of biofeedback, associated to relaxation, as a treatment of psychophysiologic insomnia, and the interest to continue its investigation in sleep and anxiety disorders.

Aim: To describe applicants for SNPD and to examine the necessity for a multidisciplinary advisory board.

Patients and Methods: Screening of patients applying to the Flemish advisory board on SNPD (SNPD-committee). Summary of the current practice of the SNPD-committee and analysis of a questionnaire investigating the attitude of clinicians on SNPD.

Results: In 7 years (2000 In 7 years ( -2006 91 application files were submitted, 65 patients received a positive advice, 50 SNPD procedures were performed. The medical history revealed that patients had tried a median of 9 antidepressants (range: 4-15), with a median of 5 (range: 3-7) antidepressant-trials conducted in adequate doses for adequate duration. Augmentation strategies with a median of 3 antipsychotics (range: 1-6) and 1 (range: 0-3) mood stabilizer were documented. Seventy-seven patients had documented trials of at least 10 sessions of Cognitive Behavioral Therapy (CBT). The median number of CBT sessions was 22 (range: 6-54). All patients had tried at least one other form of psychotherapy: family therapy (n=38); interpersonal therapy (n=17), insight oriented therapy (n=53). In 28% of the patients for whom additional treatment was recommended by the SNPD-Committee the symptoms improved to a level That SNPD was no longer required. The year-prevalence of SNPD in Belgium is 0.6/ million inhabitants, pointing out the incidental use of SNPD for severely incapacitated, treatment-refractory psychiatric patients.

Psychiatrists remain concerned about destruction of brain tissue and irreversible side effects by neurosurgical treatment. Ninetyseven percent of clinicians consider the expertise and advice of the SNPD-committee essential for indication setting. Forty-four percent of clinical psychiatrists consider referral of a patient for capsulotomy, 82% for electrical brain stimulation.

Conclusion: Neurosurgery is exclusively considered for severe, treatment-refractory psychiatric disorders. Clinicians consider the SNPD-committee essential in the decision-making process prior to intervention. Introduction: Life style intervention has shown in the general population to influence weight gain and delay metabolic complications.

Methods: ENERGIE is a lifestyle program adapted for psychiatric patients. Interactive open group sessions of 1h/week provide information about healthy food and physical activities.

Additionally healthy activities are organized. Patients did give their consent for anonymous data collection.

Results: 564 patients (54.4 % male) of all age categories have sent their follow up sheet for data entry. The median duration of the program was 84 days (0-381). Of all the patients 33.26 % were diagnosed with schizophrenia, 39 % for mood disorder and 32.60% for other psychiatric conditions. Patients had a mean illness duration of 11.17 years (0 -50 years) and dual diagnosis were not infrequent. Most patients were taking an antipsychotic drug (84.16%), 60.88% an antidepressant and 33.21% a mood stabilizer. BMI at baseline was normal in 24.51%, 33.33 % of the patients showed overweight and 42.16% obesity. Sixty-six % of the patients did complete the program and only in 2% interruption was due to dissatisfaction.

Sixty-two percent of patients found the program helpful in improving their psychological functioning. Sixty-eight percent found the program helpful in controlling their weight and 78.36 % contributed their ''feeling better'' to the ENERGIE program. Mean weight was 85, 33 kg at start of the program and 85, 17 kg at the end. More women started obese (49, 70 % vs. 36, 82 % men) , but also more women were able to change BMI category from obese to overweight (5, 65 % vs. 1, 53 % men) . Overall 3, 24 % had changed BMI category from obese to overweight (from 42, 16% to 38, and 93%).

Conclusion: Lifestyle programs can be successfully adapted for patients with psychiatric disorders and can therefore contribute in the short term to control weight as well to improve their general and psychological wellbeing. Nauczyciel C., Hellier P., Drapier D., Millet B. Affiliation Université Rennes 1, France Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive, painless new technique in the treatment of depression. Metaanalysis showed that it was more efficient than placebo and its efficacy enhanced with the knowledge of stimulation parameters. However, the target zone, the dorsolateral prefrontal cortex (DLPFC) is still located using an inaccurate standard method (SM) which might have therapeutic consequences. We needed to determinate and assess the different sources of inaccuracy of the SM before assessing therapeutic consequences. In a methodological study, we determined 3 sources of inaccuracy of the SM: cap repositioning, interjudge variability of coil positioning and distance between real and standard DLPFC. We used a neuronavigation system allowing us to locate accurately DLPFC on subject's brain and to record the coordinates of any point targeted. A healthy volunteer and 9 depressed unipolar patients were recruited: -Cap repositioning: 30 records of 1 point on the prefrontal cortex of the subject's brain after 30 cap repositioning by a trained clinician; Interjudge variability of the coil positioning, -10 records of the standard DLPFC by 10 trained clinicians, -Interindividual anatomic variability: distance between real and standard DLPFC for each subject. The methodological study showed that cap positioning was reliable with a standard deviation < 5mm in the 3 axis. The interjudge variability was important with a standard deviation > 5 mm in 2 of the 3 axis. Interindividual anatomic variability was congruent with the previous study: 50% of the patients had a distance higher than 20mm and 33% of the patients were correctly targeted. The main sources of error of the SM were the interindividual anatomic and the interjudge variability whereas cap repositioning was reliable. The neuronavigation system allowed us to correct these errors and to make reproducible studies to assess the therapeutic impact of an accurate stimulation of the DLPFC in the treatment of depression using rTMS.

subjects received a single oral dosage of either 200mg spironolactone (SP), 0.1mg fludrocortisone (FL) or placebo (PL) three hours before a stressful learning task. Number of trials, correct and false answers during the learning task and the number of correctly recalled associations at the end of the experiment were assessed.

Cortisol samples were obtained from saliva before and until 120 min. after the beginning of the stress task.

Results: The application of 200mg SP significantly increased baseline cortisol secretion compared to PL and FL. After the application of SP, cortisol secretion under stress was prolonged compared to FL. In addition, there was a trend for a better learning performance under FL.

Conclusions: Spironolactone is able to increase the basal activity of the HPA-axis and may prolong stress induced cortisol secretion. A faster learning performance under FL compared to SP suggests that the modulation of the MR-function is related to learning performance probably mediated by cortisol. Introduction: Even when people fail to recall a sollicited target, they can provide Feeling Of Knowing judgments (FOK) that reflects the ability to judge one's own memory capacity.

According to A. Koriat (1993 A. Koriat ( , 1995 , the computation of the FOK evaluations does not rely on the target answer, but on the accessibility of partial and/or contextual informations related to the target answer, irrespective of their accuracy. Cognitive deficits, as well as insight problems are today considered as core symptoms of schizophrenia. Also there are some evidences that the FOKs expressed by patients with schizophrenia differ from the controls' ratings, with patients expressing lower metamemory judgments. However, their predictive accuracy towards future recognition (G coefficient), is preserved (Bacon & al., 2001; .

Aim: The aim of the study was to see if patients with schizophrenia, as well as healthy people, rely on the products of retrieval in order to monitor their awareness about what they know and what they don't know in a task assessing episodic memory.

Patients and Methods: The accessibility to partial or contextual informations related to a memory target, as well as the relationships between the retrieved contextual informations and FOK ratings and the predictive accuracy of FOKs were investigated in 21 patients with schizophrenia and 21 matched healthy volunteers. The task was adapted from Koriat (1993) .

Results: In spite of lower global FOL estimations, patients showed a remarkable consistency between the retrieval of partial information and their metamemory ratings.

Conclusions: It seems that as well as healthy people, patients with schizophrenia rely on the products of retrieval to monitor their awareness of what they do or do not know. The different metamemory ratings of patients seem to result from their memory problem itself. Also the validity of the accessibility model of metamemory accuracy of A. Koriat was confirmed in a psychopathological context. Introduction: The pathophysiology of obsessive-compulsive disorder is still far from resolved. However, there is compelling evidence for the involvement of the frontal-subcortical circuits originating within the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively.

Aim: We tested the hypothesis that the production of compulsive behaviors results from an overactivity within these corticalsubcortical loops. For this purpose, we used a pharmacological approach primarily based on central administration of bicuculline, a GABA A antagonist, in subhuman primates. The ventral anterior (VA) and medial dorsal (MD) nuclei of the thalamus were chosen as targets for these microinjections because they are both strongly connected to the OFC and ACC. We also examined the behavioral consequences of intra-thalamic microinjections of the GABA A agonist muscimol.

Methods: Experiments were conducted on three female monkeys (Macaca mulatta). General locomotor activity and specific behaviors (grooming, food seeking, toy manipulation, and exploration) were counted using the vigiprimateÒ system (Viewpoint, France) over a 45-min period following intra-thalamic microinjections of bicuculline (20 lg/2 ll) or muscimol (2 lg/2 ll).

Results: Microinjections of bicuculline within the VA (n=8) caused repetitive motor acts including: i) seeking behaviors of food hidden in litter through the floor bars of the experimental cage; ii) meticulous and unusual manipulations of toys with thumb and index finger grip; and, iii) excessive grooming with examination and licking of various body parts, especially trunk, tail, legs, fingers… In contrast, microinjections of bicuculline within the MD (n=17) gave rise to severe symptoms of dysautonomic dysregulation including heart rate fluctuations, paleness, salivation, nausea, vomiting, urination, and defecation along with generalized body shudder, abnormal vocalizations, strong fatigue and reduced vigilance responsible for marked motor inhibition. Finally, microinjections of muscimol within the VA (n=4) and the MD (n=3) produced both a syndrome of marked hyperactivity with entirely disorganized behavioral sequences because of successive and rapid shifts from one behavior to another.

Conclusions: These findings suggest that VA is particularly involved in the production of compulsive-like behaviors whereas MD rather participates in the regulation of emotional responses. However, both VA and MD seem to play a central role in processing cognitive functions such as focused attention. Grad. Sch. Environment. and Human Sciences, Nagoya, Japan Introduction: Recently, the number of patients with atherosclerotic cardiovascular diseases has increased, raising the important issue of dysfunction of higher brain functions after the onset of cerebral infarction. Cilostazol, an antiplatelet agent used to treat cerebral infarction, inhibits platelet aggregation, increasing cerebral blood flow. Therefore, it may be effective for cerebrovascular dementia (Watanabe et al., 2006) . However, it is suggested that the apoptosis of nerves, cerebral ischemia-related inflammatory response, and oxidative stress are involved in the mechanism of cognition disorder following cerebral infarction.

Aim: In this study, we investigated the effects of cilostazol on learning and/or memory impairment induced by the administration of b-amyloid peptide (25-35) to mice, in which apoptosis and oxidative stress may also be involved (Medeiros et al., 2007) , from the perspective of behavioral pharmacology.

Animals and Methods: In our experiment, we conducted spontaneous alternative behavior (Y-type maze) and passive avoidance tests after the administration of b-amyloid peptide (25-35) (9 nmol/mice, i.c.v.) using 7-to 9-week-old ddY mice (Hiramatsu et al., 2000) to evaluate the effects of cilostazol on learning and/or memory functions.

Results: Continuous administration of cilostazol (30 and 100 mg/kg, p.o.) for a few days (from the administration of b-amyloid peptide (25-35) until the day of our experiment) significantly inhibited learning and/or memory impairment induced by b-amyloid peptide (25-35). Another antiplatelet agent, aspirin (30 and 100 mg/kg, p.o.), did not show such effects. Neither single-dose administration of cilostazol nor its continuous administration before b-amyloid peptide (25-35) administration prevented learning and/or memory impairment.

Conclusion: As cilostazol inhibits apoptosis, it may have reduced b-amyloid peptide (25-35)-related learning and/or memory disorders via an action mechanism differing from the inhibition of phosphodiesterase III. In the future, the involvement of inflammatory cytokines and oxidative stress should be examined.

APPLICATIONS OF NAVIGATED TMS AND EEG Zanow F. Eemagine Medical Imaging Solutions GmbH, Berlin, Germany TMS technology has become widely available as a stimulation device in the investigation of brain functions. Applications such as the examination of facilitatory and inhibitory processes within the motor cortex, the effect of attentional manipulations on those processes, or therapy-induced changes in cortical plasticity following stroke have become possible with the use of navigated TMS, which allows precise positioning and dosage of nerve excitation in the brain.

We introduce the technology of navigated TMS and show examples of simultaneous EEG analysis that reveal the power of this tool in research and diagnostic applications.

Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) is a widely used technique for source localization. However, this technique still has some limitations, especially under realistic noisy conditions and in the case of deep sources. To overcome these problems, we present here swLORETA, an improved version of sLORETA, obtained by incorporating a singular value decomposition based lead ) eld weighting. We show that the precision of the source localization can further be improved by tomographic phase synchronization analysis based on swLORETA. Phase synchronization analysis turns out to be superior to standard linear coherence analysis, since the latter cannot distinguish between real phase locking and signal mixing. It has been proposed that, in schizophrenia, basic cognitive impairments like masking represent a vulnerability factor originating disorders in more complex cognitive functions. However, how such impairments relate with each other remains to be unravelled. Here we propose to explore the ability to distinguish events in time, basing our approach both on phenomenological issues that relate time with consciousness and on an experimental approach allowing to evaluate judgments of simultaneity in patients. The choice of this paradigm is motivated by the fact that performance is independent from a memory, persistence or bias effect. It thus allows to isolate a time component more easily than duration evaluation or masking. Two bars are displayed on a computer screen, and participants judge whether they are simultaneous or not. Simultaneity judgments are contrasted with the effects of subthreshold priming, which influences simultaneity judgments. Nineteen outpatients and their individually matched controls, participated in the study. Patients showed higher thresholds than controls in all tests. This contrasted with subthreshold priming effects, which were uniform across groups and allow to eliminate an effect of bias. Subjective evaluation of simultaneity is impaired in patients. Whatever the origin of this impairment it may have a large impact on cognitive functions, inasmuch the normal consciousness flow requires the integration of successive moments, past, present and future. The present results suggest that these 'moments' are enlarged in patients. The method used in the present study represents an original way to asses disturbances related to time in patients with schizophrenia. Processing visual information involves automatic grouping processes and top-down attentional processes that help to reorganize information. Many studies have now suggested that grouping in vision is impaired in patients with schizophrenia, but without distinguishing between automatic and top-down processes. We used a paradigm derived from Beck and Palmer (JEP, 2002) in 30 patients with schizophrenia and 30 matched controls. Subjects decided whether series of stimuli with geometrical features included, or not, two consecutive identical stimuli. The manipulation of proximity defined pairs of two figures. Patients, like controls, benefited from grouping by proximity: they were faster and more accurate when the two identical stimuli belonged to the same group than to different groups of figures. However patients had difficulties reorganizing information. Reorganization of information was explored by means of three experimental blocks that were defined by the percent of target-present trials where the targets belonged to the same pair (within-group trials) or to different pairs (between-group trials): 25-75%, 50-50%; 75-25%. Recordings of ocular movements and behavioural data showed that healthy volunteers control the exploration of between-group regions independently from within-group regions. Hence healthy volunteers were able to prioritize selectively objects even if they were part of different groups. Patients were able to prioritize pairs of objects defined by proximity when targets belonged more frequently to the same pair. This shows that they take into account the experimental manipulations as well as controls. However, they were unable to prioritize objects that were part of different groups selectively. The results suggest that healthy volunteers create a representation involving pairs of figures that belong to different groups. Such representations help to focus on group parts without fragmenting information. Patients with schizophrenia appear to be impaired in the building of such representations, which might severely impact on the way they explore and adapt to a complex environment. Purpose: Recent research on RBC membrane in patients with schizophrenia showed a significant increase in the percentage of phosphatidylethanolamine (PE) on the external membrane leaflet. Increase in the external PE percentage was found in 2/3 of a schizophrenia population (n=65). Age, sex and antipsychotic treatment were not associated with this PE abnormality. This result could be associated with the membrane lipid modifications described in the patient with schizophrenia population, showing in particular a total membrane PE and PC decrease along with a compensatory PS increase. Membrane abnormal PE distribution is under scrutiny as it seems to be a stable trait associated with the disease or some of its endophenotypic characteristics. Both bipolar disorder (BP) and schizophrenia (SCZ) are multi factorial diseases likely to share common biological predispositions. A recent publication studying the sPLA2 activity, an enzyme involved in membrane modelling and known to be increased in serum of schizophrenia patients, showed an increased activity only in bipolar patients with a history of psychosis. It suggests a possible association between PL metabolism and endophenotypic psychotic manifestations (Ross et al., 2006) . We wanted to address the question whether the PE membrane biomarker described in patients with schizophrenia could also exist in a subgroup of bipolar patients in particular those with a history of psychosis. In order to address the first point, a membrane PE distribution analysis was performed on RBC membranes from patients suffering from bipolar I disorder.

Method: RBC from age and sex matched patients with bipolar disorder (n=5), schizophrenia (n=5) and healthy controls (n=5) were collected. RBC membranes were isolated and labelled using TNBS (trinitrobenzensulfonic acid) a colorimetric probe able to specifically label the externally located PE. Membrane phospholipids were extracted by the method of Bligh and Dyer. Liquid chromatography mass spectrometry (Q-Trap LC-MS/MS) was performed to analyse membrane phospholipids ratio. PE molecular species from each leaflet were analysed and compared for the two patients' population.

Results: An abnormal PE distribution was found in the RBC membrane of 1 patient with bipolar disorder. This patient was the only one among the 5 BP individuals with a history of psychosis. Research in a larger bipolar population is needed to validate this finding. Introduction: Cortisol secretion is closely related to stress stimulation and learning and memory processes.

Aim and Methods: In order to establish a new standardized learning paradigm, which is able to provoke a stress reaction, we applied a computerized pair-association learning task in 48 healthy male subjects (age 18-34 years). The task was performed without (control condition) and with a) time limitation and b) the possibility to gain extra money in case of excellent performance (stress condition). Both conditions were randomly assigned and completely balanced. The number of trials participants needed to recall all pair-associations within one trial and the averaged number of errors per trial were assessed. The number of correctly recalled associations after 1,5 hours delay was available in 22 participants. Cortisol samples were obtained from saliva before and up to 1,5 hours after the learning task. Blood pressure and heart rate as well as subjective mood (BSKE-scale) and vegetative symptoms (MSKLscale) were measured before and after the learning task.

Results: The stressful learning condition resulted in a significantly higher cortisol response compared to the control condition and showed significant effects on systolic as well as diastolic blood pressure and heart rate. Correspondingly, stress related items of subjective mood (tension and anger), and vegetative symptoms reflecting sympathetic nervous system activity increased significantly. Cortisol increase during stressful learning was not related to general learning performance, but to the number of trials needed to perfect task performance.

Although delayed recall was slightly superior in the stressful learning condition, there was a trend that subjects with a stronger cortisol response during stressful learning performed worse in delayed free recall. Increase in diastolic blood pressure was slightly associated with lower task performance. Good learning performance was somewhat associated with subjective well-being, whereas lower performance was associated with restlessness and moroseness. In contrast, no correlation of learning performance with subjectively experienced vegetative symptoms was found.

Conclusion: In summary, the stressful learning task applied in this study was able to provoke a stress response in young healthy volunteers on the endocrine, cardiovascular and subjective level, somewhat affecting learning and memory performance. Introduction: Movement is strongly influenced by the cognitive and emotional context in which it takes place. Basal ganglia are known to be implicated in motor functions. Current models suggest that these structures are also implicated in cognitive and emotional processing (Alexander 1980; Parent 1986) . Although the exact nature of the processing of motor, cognitive and emotional modalities in the basal ganglia is still unknown, several observations from high frequency deep brain stimulation (DBS) and neuroimaging suggest that the subthalamic nucleus (STN), a basal ganglia nucleus which is part of the striato-pallidonigral pathways, operates some kind of integration of motor, emotional and cognitive information (Mallet 2007) .

Aim: To determine how the STN is implicated in emotional and cognitive processing at the level of neuronal assemblies in human.

Patients and Method: Local field potentials (LFP) were recorded in the STN of 5 parkinsonian patients that underwent bilateral electrode implantation in the STN for DBS.

Recordings were made while the subjects were executing an emotional and decision task, in on and off dopa conditions. The task implying emotional, metacognitive and motor processing, was based on a go-no go paradigm, with emotional (positive and negative) and neutral pictures as stimuli. Subjects had to decide whether a picture was emotional or not, and to indicate or not indicate their decision, according to the instruction given, as a motor response.

Results: Both the presentation of the picture and the motor response evoked a potential in the STN. For the picture presentation, the STN evoked potential has a mean latency of 150 ms and reached his maximal amplitude at 450 ms. Evoked potentials were significantly larger for emotional than for neutral pictures. In all patients, STN emotional evoked potentials recordings were obtained from contacts localised within the associative territory of the STN (Yelnik 2007) .

Conclusion: These results suggest that emotional and cognitive information is processed in the same subterritories in the STN, suggesting a certain degree of integration of motor, cognitive and emotional information in the STN. 3. Mallet L, Schupbach M, N' Introduction: Clinical investigations in obsessive-compulsive disorder (OCD) have proposed that the internal perception of error generating pathological doubt plays a major role in the production of compulsive behaviours (1, 2) . Aim: The present study concerns the objective and quantitative measurement of checking activity, which represents the most frequently observed compulsions. To address this issue, we developed an instrumental task producing repetitive checking in OCD subjects.

Patients and Method: Fifty OCD patients with or without intensive checking compulsions (OCD CC+: n=36; OCD CC-: n=14, respectively) and 50 age-and sex-matched normal volunteers (NV) were administered a delayed matching-to-sample task that offered the unrestricted opportunity to verify the choice made. Response accuracy, number of verifications, and response time for choice taken to reflect the degree of uncertainty and doubt, were recorded over 50 consecutive trials.

Results: Despite similar levels of performance, OCD CC+ demonstrated a significantly greater number of verifications than OCD CC-, yet both experienced more intensive checking than NV. Furthermore, OCD CC+ showed a significantly longer response time for choice before checking than NV, whereas OCD CC-did not. Although there was a gradual rise in the number of verifications throughout the task in both OCD subgroups, only OCD CC+ differed from NV in their behavioral profile.

Conclusions: The present task might be of special relevance for the quantitative assessment of checking behaviors and for determining relationships with cognitive processes. Such an experimental approach might be useful for further studies focused on the identification of the neurobiological substrates of checking. Introduction: The term of Theory of Mind (ToM) has been coined in reference to the capacity of inferring mental states (1) . A conceptual approach, Relational Frame Theory (RFT), has tried to investigate perspective-taking skills, a capacity to adopt someone different points of view among temporal, spatial and interpersonal dimensions. According to RFT, perspective-taking skills are needed to infer others' mental states (2) . Patients with schizophrenia show difficulties in inferring mental states (3) . This impairment could be involved in delusion of persecution (4) and in disorganized thought (5) . Schizotypy, a personality disorder with proneness to schizophrenia, shares characteristics with this illness on several dimensions (6) . Impairments in ToM have also been observed in this population (7) . RFT view has never been tested neither in schizotypy nor in schizophrenia.

Aim: Testing spatial, temporal and interpersonal perspectivetaking in people scoring high on social anhedonia, a common characteristic of schizotypy and schizophrenia.

Participants and Methods: 30 Participants scoring high on Social Anhedonia Scale (SAS -8 ). 30 participants with a modal score on the same scale. In a previous study, we observed that social anhedonia is involved in social abilities, since score on SAS discriminate people with and without ToM impairments (9) . Social anhedonia may predict ToM impairments. In this task, participants have to change perspective on three levels of difficulty (simple, reversed, double-reversed perspective-taking). For example, the higher level of difficulty was: ''I was sitting then, on the blue chair and now I'm sitting here on the black chair. If here was there and then was now: where would I be sitting now?'' A ToM task based on (10) was also proposed.

Results: Participants scoring high on SAS were significantly less accurate than controls on double-reversed perspective-taking questions (p<0001); no difference appeared on reversed questions. Results revealed a correlation between perspective-taking and ToM performances for all participants (r=0.64; p<0.0001). IQ does not account for these results since there is correlation between Raven's Progressive Matrices and perspective-taking scores (r=0.073, p>0.05).

Conclusion: Results supports the view that perspective-taking skills are at the core of ToM abilities and should be specifically investigated in schizophrenia to understand ToM impairments, and possibly extend remediation. mind'' in people with schizophrenia. Schizophrenia Research, Introduction: Impaired recognition of facial expression has been largely observed in schizophrenia (Edwards & al., 2002) but has never been studied as a possible consequence of visual impairments. Several studies have proposed a dysfunction of the magnoand parvocellular pathways (Butler & al., 2005) , involved respectively in the treatment of low-and high-spatial frequencies (LSF and HSF). In normal control subjects, different spatial scales tend to convey different information for recognition of facial expressions (Schyns & al., 1999) .

Aim: We test the hypothesis that visual dysfunctions in schizophrenia may impair the processing of spatial frequencies and thus affect the recognition of facial expression.

Patients and Methods: 16 patients with schizophrenia and 15 normal control subjects performed 2 experiments. In experiment 1, they performed 2 different tasks with hybrids stimuli, combining a face in HSF scale and another face in LSF scale. Because each face presented a different expression, the response allowed us to infer which spatial scale was preferentially perceived. In experiment 2, we used filtered stimuli, presenting a single face filtered on HSF or LSF.

Results: We observed with hybrid stimuli a LSF bias on each task for patients with schizophrenia whereas control subjects presented a HSF bias. In experiment 2, there was no significant difference between performances of patients with schizophrenia in LSF or HSF.

Conclusion: These results indicate a preferential LSF treatment of faces in schizophrenia (experiment 1) and this preferential treatment was not due to a HSF perception deficit (experiment 2). These results can not be explained by a magnocellular perceptual deficit but suggest a higher-order deficit involving integrated magno-and parvocellular informations. Introduction: Disorder of consciousness has been pointed to explain several symptoms in schizophrenia. Hallucinations might be internal representations raising to conscious perception, and wrongly classified as externally generated. Neural correlates of conscious vision have been studied in healthy subjects. Some results suggest that a fronto-parietal network interacts with visual cortex to enable conscious access to visual processing (1).

Aim: Our aim was to investigate neural correlates of visual consciousness in schizophrenia.

We made the assumption of a disorder of conscious access, which could be reflected by an over-activity of the fronto-parietal network involved in conscious access, and so could facilitate hallucinations.

Patients and Methods: An event related fMRI paradigm was used with a visual detection task (2) . Presented at threshold, a same stimulus allows switches between conscious and unconscious visual processing. By comparing neural activity between these ''conscious'' and ''unconscious conditions'', we investigated neural correlates of visual consciousness in 10 healthy subjects and 10 schizophrenics.

Results: Patients had higher detection thresholds than healthy subjects. Our results showed differences in brain activity between patients and healthy subjects, regarding to the neural network involved in visual consciousness. Patients displayed hypo-activations of subcortical and limbic areas (insula, hippocampus, thalamus), but over-activations of a cortical fronto-parietal network. Moreover, positive symptoms were correlated with an increased activity of visual areas.

Conclusion: Our results confirm a disorder of conscious access in schizophrenia. Hypoactivations might be explained by a deficit in early stages of sensory integration (3), whereas overer-activations might reflect an attentional compensatory mechanism. Further studies of conscious and unconscious perception processing could be a relevant way to understand symptoms in schizophrenia. Introduction: Visual scanning of faces is known to be impaired in schizophrenia. Patients with schizophrenia usually make fewer fixations than healthy controls on salient facial features and their exploration duration is reduced. However, previous studies (e. g., Bestelmeyer et al., 2006) have examined visual scanning under passive viewing conditions. Aim: Our study was designed to examine whether individuals with schizophrenia are able to control the spatial orientation of their attention when they are guided by instructions.

Patients and Methods: Visual scan paths were measured in patients with schizophrenia (n=20) and control participants (n=20) by means of an eye tracker (Senso-Motoric Instruments). Participants started with a ''free viewing'' task of faces followed by tasks in which they were asked to determine the gender, the facial expression, estimate the age and decide whether the face was known or unknown. Temporal and spatial characteristics of scan paths were compared for each group and task.

Results: The ''passive viewing'' task induced fewer fixations and longer fixation durations than the ''active viewing'' tasks for the two groups. In comparison with controls, patients with schizophrenia exhibited reduced attention to salient facial features in passive viewing condition, but did not differ from controls in the active viewing conditions.

Conclusion: This study shows an improvement of facial exploration in patients with schizophrenia when they are guided by instructions. This improvement can be explained by a better control of the spatial orientation of their attention. Introduction: Patients with Borderline Personality disorder (BPD) and with Anxiety Disorders (AD) contrast in personality traits and behavior. According to Gray, impulsivity and anxiety are independent traits characterized by a different susceptibility for stimuli of reward and punishment. These traits have been related to serotonergic and dopaminergic neurotransmission. Aim: To further elucidate this relationship, we investigated personality traits, behavioral performance and neuroendocrine responsiveness to serotonergic and dopaminergic stimulation in patients with BPD and AD.

Patients and Methods: 30 Patients (AD: N = 15; BPS: N = 15) had to complete personality inventories (e.g. NEO-FFI, TCI) and underwent an approach-avoidance paradigm in which reward and punishment were systematically varied. Furthermore, a serotonergic (oral citalopram 20mg vs. placebo) and dopaminergic (oral bromocriptin 1.25mg ) challenge test assessing cortisol and prolactin was performed.

Results: Cortisol and prolactin were significantly more stimulated by citalopram in BPD compared to AD. No differences between groups were observed in the dopaminergic stimulation. The approach-avoidance paradigm revealed a significant better performance in the condition, in which reward could be easily achieved for BPD compared to AD.

Conclusion: Patients with AD und BPD differ in personality traits and show a different neuroendocrine response according to citalopram stimulation. The observed difference in serotonergic neurotransmission may be related to personality pattern and performance. Introduction: Reaction Time (RT) slowing down is observed in Alzheimer's disease and schizophrenia. RT analysis through cognitive models of stimulus processing allows to estimate mental steps duration, postulated in cognitive models. Computerized paradigms measuring visual stimuli RT have been developed and analyzed through a cognitive model derived from that of Bonnet (1989) .

Aim: The aim of this study was to analyse and compare the impaired cognitive processes in schizophrenia and Alzheimer's disease.

Patients: 14 Healthy young subjects; 36 healthy elderly subjects; 15 young schizophrenic patients; 16 middle-aged schizophrenic patients and 13 patients with mild Alzheimer's disease were included.

Methods: RT paradigms include: simple visual reaction time (TRV) ; Visual Backward Masking (VBM) ; Mnemonic Visual Prospection; Visual Prospection using two SOA (0 ; 600 ms). Same stimuli were used in all paradigms as response mode except for the VBM. The analysis was done on correct responses only (ANOVA). It concerns TRV, the durations of stimulus structuration and its mental representation elaboration, SOA sensitivity and modality effect (difference between « Different » and « Identical » responses).

Results: The main results were: 1) in the 3 pathological groups: a 30-50% slowing down of central steps of the visual processing with a slight structuration lengthening but without mental representation elaboration lengthening; 2) a dramatic SOA sensitivity decrease in schizophrenic groups whereas an important increase is observed in the Alzheimer group; 3) the modality effect was by far higher in the Alzheimer group compared to this in the schizophrenic and control groups.

Conclusion: According to the cognitive model, these results suggest that visual processing dysfunction occurs later in Alzheimer than for schizophrenic patients. It lies in conscious steps in Alzheimer's disease and in unconscious processes in schizophrenia maybe the mental representations automatic managing.

Reference 1. K. Le Roch'h and al., 1995. La Presse Médicale, 24 supp.16:12-18; C. Sebban and al., 1998. L'Encéphale, 190-4 ; E.Eusop and al., 2001. L'encéphale, 26:39-44 ; S.Schumm and al., March 2007. Schizophrenia Bulletin, 33, 2. Methods: Cross-sectional survey in 14 Belgian psychiatric hospital pharmacies. Information was collected for patients treated since at least 6 weeks with AAP (N=1828) in 2007 about demographics, DSM-IV diagnosis (axis 1), and dosages of AAP. The data were compared with a similar study in 2003.

Results: 1828 patients are included. 59% are male. The mean age is 48 years. The diagnosis of schizophrenia diminishes from 63% in 1999 to 52.4% in 2003 and 52.2% in 2007. AAP therapy is also used in dementia (5.2%), depression (7.7%), bipolar disorders (4.7%) anxiety (1.2%), and in other diagnoses (29.1%).The mean daily doses have evolved: Clozapine 388mg (394mg in 2003), Olanzapine 16.6mg (14,4mg) , Risperidone 4.0mg (4.2)mg, Risperidone inj. LA 3.1mg. Quetiapine 565mg (552mg), Amisulpiride 560mg (498mg), Aripiprazole 14.6mg. The doses of AAP are higher in schizophrenic patients than in non-schizophrenic patients. The progression is more marked in the schizophrenic group. The doses remain higher than the Defined Daily Dose (DDD) with exception for oral Risperidone and Aripiprazole. Obviously, the costs progress in the same trend.

Conclusions: Demographic data and indications remain similar. Psychiatrists prescribe always AAP in more different disorders than expected. The doses of AAP for in-patients are superior to their DDD, with exception for oral Risperidone and Aripiprazole. Except clozapine and oral risperidone, AAP dosages are always in augmentation with an underlying financial load. Method: Cross-sectional survey in 14 Belgian psychiatric hospital pharmacies. A one shot review of treatments of patients on atypical therapy since at least 6 weeks was performed. Demographic data, DSM IV diagnosis (axis 1) and dosages of AAP's were collected. Typical neuroleptic drugs (e.g. prothipendyl, levomeprom-azine…) only used as hypnotic (i.e. one single dose at evening) are not included. Data were compared with a similar study in 2003.

Results: 1828 patients were included (59% M., mean age: 48 years). 52.2% are diagnosed following schizophrenia or psychotic disorders criteria (S/PD). 75.9% (2003: 91,4%) received one AAP and 22.3% (8,5%) received two AAP's. 41% (43.5%) received at least one typical with 48% (49%) in the S/PD group. 24% (30%) received at least one anticholinergic drug with 32% (35.7%) in the S/PD group. 39 .3% (44%) of patients received one single AAP (without typical and anticholinergic drugs) but only 26.8%(37%) for the S/PD group. 3 .6% (7,5%) of the patients on AAP monotherapy still received one anticholinergic (11,5% in1999). 57% (48,2%) of the patients on AAP received at least one other antipsychotic (AAP and Typicals).

Conclusions: Polypharmacy is very frequent among hospitalized patients in psychiatric hospitals and the rate of association of AAP and typical antipsychotics is nearly the same in 2007. The ''pure'' AAP monotherapy has decreased from 51.8% to 43% in 2007. Overall use of anticholinergic drugs is reduced. Contrary to the international guidelines, we clearly see an increase in the atypical antipsychotics association without a decrease of the use of typical antipsychotics, and with a risk of adverse drug reactions. Financial loads are worsened by growing dosages and by associations of expensive drugs. Introduction: There is a growing body of evidence that oxidative stress, caused by reactive oxygen species, plays a substantial role in the pathophysiology of psychotic disorders. Altered activities of antioxidant enzymes are described in drug naive schizophrenic patients as well as in patients treated with antipsychotics.

Aim: The purpose of the present study was the examination of effects on the expression of the key enzymes of antioxidant metabolism after treatment with haloperidol and quetiapine.

Methods: The effects of haloperidol and quetiapine were tested in concentrations of 0.3, 3, 30 and 300 lM in the human neuroblastoma SH-SY5Y cell line after 24 hours of incubation. The investigated enzymes were Cu, Zn superoxide dismutase, Mn superoxide dismutase, glutathione peroxidase, and catalase via reverse transcriptase polymerase chain reaction.

Results: Within the scope of the present study, we observed merely significant decreases of mRNA contents. We detected especially significant effects on the expression of the hydrogen detoxifying enzymes (glutathione peroxidase and catalase) after treatment with both substances. All used concentrations exerted impacts. Examinations of the superoxide dismutase isoforms revealed only significant effects after treatment with the higher antipsychotic concentrations.

Conclusion: Our findings demonstrate that antipsychotics are able to exert a wide range of effects on the expression of the four key antioxidant enzymes. Introduction: Alterations of antioxidant enzyme activities are found in various psychiatric diseases like major depression. Also treatment with antidepressants leads to altered antioxidant enzyme activities.

Aim: The target of the present study was to investigate the effects of treatment with different antidepressants (desipramine, imipramine, maprotiline, and mirtazapine) on the expression of the key enzymes of antioxidant metabolism.

The impacts of antidepressants were tested in concentrations of 10 )5 , 10 )6 and 10 )7 M in the human monocytic U-937 cell line after 2.5 and 24 hours of incubation. The investigated enzymes were Cu, Zn superoxide dismutase, Mn superoxide dismutase, glutathione peroxidase, and catalase via reverse transcriptase polymerase chain reaction.

Results: After short-term treatment significant decreases of mRNA levels of both superoxide dismutase forms, glutathione peroxidase, and catalase were found. In addition, after long-term treatment significant increases were seen in the cases of Cu, Zn superoxide dismutase in concentrations of 10 )7 M.

Conclusion: Our findings demonstrate that antidepressants change antioxidant enzyme expression. The alterations of antioxidant enzyme expression could be a possible target for the action of antidepressants. Mathot F., Noel Ch. Centre Hospitalier Psychiatrique, Pharmacy, Liège, Belgium Introduction: Our daily practice confronts us with large differences, sometimes paradoxical, in the therapeutic practices with frequent inadequacies between the recommended guidelines and the real practice. We are often faced with comorbidities, interface between psychiatric and somatic pathologies, long pharmacological history with various therapists, useless medical excess loads and pharmacological accumulation.

Aim:

The medico-pharmaceutical staffs should try to improve the quality of the pharmacotherapy of their institutions and they should feed the data of pharmacovigilance.

Better is the medical treatment, better is the tolerability and so, the observance and the quality of life (QoL) of the patients. The aim is to bring to the patient the most rational pharmacotherapy.

Method: We get together psychiatrist, somatician, nurse and clinical pharmacist with the databank Drugdex°. All treatments are revised with the necessary detachment and reflection for an optimalised use of the drugs. The interventions, recommendations, follow-ups and results are encoded on a database for the tracability.

Results: After 8 years of functioning, 4763 treatments were revised with 1269 interventions for 833 patients. The results are positive for:the patient: he benefits from a better clinical judgment thanks to a control which can only improve his therapy; evident interests for the QoL, for instance, for 377 propositions for stopping some medications, 367 were followed; for 214 dose adjust proposals, 199 were agreed. -the doctors are conscious of the positive aspect of these meetings thanks to the contribution of different multi-field sensibilities without the pressure of urgency. They are consolidated in their prescriptions thanks to Drugdex°with EBM criteria. -the nursing: the explained medicine reassures the nursing as well as the transparency of the dialogues of the three resource present persons. The numerous exchanges often allow to recover certain underlying problems.

-The pharmacist is comforted by a better use of medicines with a real and effective surveillance. Drug management is facilitated. -the Health Service can obtain more pharmacovigilance data and can better estimate the use of therapeutic decision-making trees (EBM). It can also better control the financial loads (pharmacoeconomy).

Conclusion: This experience tends to demonstrate that, with sufficient human and technical means, a hospital pharmacy is susceptible to improve the quality of the pharmacotherapy.

Schwan R., Luthringer R., Llorca P.M., Zannad F., Gailledreau J. EDDH, Nancy, France In March 2000, the Lisbon Council defined the development of the most competitive and dynamic knowledge-based economy in the world as a strategic goal. Pharmaceutical innovation and clinical research add a significant value to this development, both in public and private health sectors. However, the European Commission noted in 2001 in a report analysing the competitiveness in European Pharmaceuticals that: ''Europe is lagging behind the USA in its ability to generate, organise and sustain innovative processes that are increasingly expensive and organisationally complex''. Since new and innovative medicines should be available to European patients as quickly as possible, this flaw in the EU treatment development has become not only an industrial problem, but a major politic concern. One of the identified structural Achilles 'heels provoking the erosion of clinical research in Europe is that research and development in EU is hindered by fragmented research systems and a lack of coherent and integrated approach between public and private sectors. In the same time, the United States of America have undoubtedly succeeded in co-ordinating public and private research, especially in clinical trials. Part of the reasons for its success relies in relative facility of cooperation between public and private institutions strengthened by the pragmatic action of the National Institutes of Health. In France as well as in many EU countries, public institutions have to jump over huge inconveniences in setting up and conducting clinical trials, and consecutively obtain poor competitiveness. In parallel, despite private groups of investigator are able to conduct large clinical trials in an efficient manner, they often lack studies for which they are available. However the French Government tries to create modern legislative framework and initiatives to ensure that public and private sectors will operate smoothly. The present presentation will examine these various initiatives like PHRC, Clinical Investigation Centres, foundations, contribution of private groups of investigators… in a European perspective. Aim: To assess at the population level whether the prescription of antidepressant drug treatment in real-life settings is associated with an increased or reduced risk of suicide relative to the absence of antidepressant drug treatment in depressed patients.

Methods: Decision analysis method was used to estimate the number of suicides prevented or induced by the antidepressants in patients diagnosed with major depression in children and adolescents (10-19 years old), adults (20-64 years old) and elderly (65 years and older).

Decision analysis is a modelisation method based upon a probabilistic Bayesian approach allowing to compare in a target population the risks and benefits of two extreme therapeutic scenarii. The population impact may be estimated by using a virtual randomisation of all subjects from the general population between these therapeutic strategies, without being restrained by ethical issues. The modelisation is based upon ''real'' data and applied to a ''real'' population. However, ''realistic'' assumptions were made when no data were available for some specific estimates. The impact of gender and parasuicide history on the findings was explored within each age group. Sensitivity analyses were used to assess the robustness of the models.

Results: Prescribing an antidepressant therapy to all patients diagnosed with depression would prevent more than one out of three suicide deaths compared to the absence of antidepressant strategy, irrespective of age, gender or parasuicide history. Sensitivity analyses showed that persistence in taking antidepressant therapy would be the main characteristic influencing effectiveness of ADT on suicide risk.

Conclusions: Public health decisions that directly or indirectly contribute to reducing the number of patients with depression who are effectively treated by antidepressants may paradoxically induce a rise in suicide deaths.

CATATONIA SYNDROME AFTER DELAYED CLOZAPINE WITHDRAWAL: A CASE REPORT Grès H., Haouzir S., Desbordes M., Lemoine X., Guillin O., Petit M. Dept. of Psychiatry, University of Rouen, Rouvray Hospital, Sotteville Lès Rouen, France Introduction: Caution has been recommended with the use of first generation antipsychotic drugs in catatonia. Interestingly, it is suggested that patients with catatonia might favorably respond to second generation antipsychotics and catatonia emerging during abrupt withdrawal of clozapine have been reported. Therefore, gradual tapering has been recommended. Here, we report for the first time the case of a patient who presented a catatonic episode after gradual tapering of treatment by clozapine.

Aim: To discuss the role of clozapine withdrawal in inducing catatonia after gradual tapering of this drug.

Results: Mr L., a 43-years-old man, was hospitalized for delirious exacerbation of a schizo-affective disorder (according to DSM-IV). The patient was treated with clozapine (200-450 mg/day) for more than one year. The poor tolerance and efficacy of clozapine lead us to stop this treatment. Thus, a gradual discontinuation over four weeks was done. Three weeks after discontinuation, Mr L. displayed a stuporous catatonic state with verbigerations, fading, speech rare and irrelevant, cataleptic postures, catalepsy, waxy flexibility. All catatonic features resolved spontaneously within forty eight hours.

Conclusion: The role of clozapine withdrawal in inducing the catatonic condition could be argued on: i) this patient had no past history of catatonia ii) Extensive clinical and paraclinical investigations failed to reveal any other possible cause to this catatonic syndrome iii) the existence in literature of similarly cases resolving after clozapine reinstatement, iv) at the time catatonia features appeared clozapine is supposed to be completely cleared from the brain.

This case differs from previous reports because it occurred at a more delayed time and no cholinergic hyperactivity signs were observed. This leads to the hypothesis that catatonia occurring after gradual discontinuation and after abrupt withdrawal are not supported by the same neurobiological mechanisms.

SEROTONIN SYNDROME ASSOCIATED WITH SERTRALINE MONO-THERAPY AT THERAPEUTIC DOSES Ozdemir S. 1 , Yalug I. 2 1 Istanbul University Cerrahpasa Medical Faculty, Dept. of Psychiatry, Istanbul; 2 Kocaeli University Medical Faculty, Dept. of Psychiatry, Kocaeli, Turkey Introduction: Serotonin syndrome is a serious and potentially lifethreatening medical condition due to serotonergic hyperstimulation and it has been characterized by mental status changes, neurologic abnormalities and autonomic instability. It usually results from combination of serotoninergic agents; however monotherapy can also elicit this condition in some cases.

Aim: We aimed to report the onset of serotonin syndrome in a patient who was treated with only sertraline, a selective serotonin re-uptake inhibitor.

Patients and Methods: A 66-year-old man was diagnosed with major depression and sertraline was commenced at 50 mg once daily. 6 weeks later, he was admitted to our psychiatric outpatient's unit with the complaints of irritability and agitation, palpitation, sweating, shivering, subjective fever and flushing, fatigue, dry mouth, insomnia, weight loss, probably due to lack of appetite and dysphagia for solid foods, and constipation.

Results: On presentation, he was alert, fully orientated, and could follow commands, but he was seemed to be apparently anxious, restless and extremely diaphoretic. He was unable to stand up without assistance. On physical examination, his arterial blood pressure was 140/90 mmHg, heart rate was 110 bpm, respiratory rate was 18 breaths/min, and tympanic temperature was 36.5°C (97.7°F) . Neurological examination revealed bilateral slight papillary dilatation, tremors in rest, ataxia, symmetrical hyperreflexia of extremities, and multifocal myoclonus predominantly in both of his lower extremities. No extremity rigidity was present. The rest of the neurological examination was essentially normal. Routine blood chemistry, a complete blood count and urine analysis revealed no significant changes from baseline. All the findings were consistent with mild serotonin syndrome and sertraline was suspected as the possible causative agent.

Conclusion: Diagnosis of serotonin syndrome is based on clinical presentation, history of serotoninergic agent use and the exclusion of other potentially causative conditions. Serotonin syndrome due to a single serotoninergic agent is a rare condition and there have only a couple of cases been reported up to date. We recommend that the physicians should know the diagnostic criteria of this syndrome and should have a lowered threshold to make the diagnosis. A 72-year-old patient with probable diffuse Lewy body disease (DLB) who developed a dropped head syndrome is presented. 1 Noticeable head flexion started after two days treatment with the atypical antipsychotic olanzapine which was initiated because of severe confusion, delusions and visual hallucinations. The patient could maximally lift her head 20 degrees. Painful neck rigidity was noticed, particularly in case of backward extension (video fragment 1). One week after olanzapine withdrawal, the patient's posture started to improve slightly (video fragment 2). From time to time, the patient was able to drink with nearly full neck extension, which was interpreted as being a sensory trigger. Repeated needle electromyography showed marked myopathic changes in dorsal paraspinal muscles and sustained contraction of the right splenius capitis muscle. Further improvement was achieved by starting a treatment with benserazide-levodopa. Because of peak-dose dyskinesias, entacapone was associated. Because of persisting severe delusions despite treatment with a maximal daily dose of rivastigmine, aripiprazole 10 mg was started. Four months later, a remarkable recovery of the head drop was noticed (video fragment 3). In conclusion, this is the first report of a case with dropped head syndrome in a patient with DLB. Dropped head syndrome has been reported in Parkinson's disease and multiple system atrophy. 2, 3 Its underlying pathophysiology remains to be elucidated. Our clinical and electrophysiological observations suggest neck extensor myopathy due to axial rigidity or focal neck dystonia, induced by dopamine receptor blockade. This hypothesis is underbuilt by the fact that improvement was achieved after withdrawal of olanzapine and following the start of a treatment with levodopa. Due to its partial dopaminergic agonistic effects, treatment with aripiprazole might have had beneficial effects too.

Koener B., Hermans E., Constant E.L., Maloteaux J.M. Dept. of Psychiatry, Cliniques Universitaires St-Luc, Laboratory of Experimental Pharmacology, Brussels, Belgium Antidepressant drugs have been evolving, from the TCAs, to the SSRIs and more recently the norepinephrine selective reuptake inhibitors (NRIs). Indeed, the serotoninergic system has a crucial role in both depression and anxiety, but the implication of norepinephrine remains debated. On a clinical point of view, NRIs and SSRIs improve rates on the Hamilton scale as well as on the social adaptation and self-evaluation scale. But, considering the items as social functioning, interests and motivation, NRIs seem more efficacious than SSRIs, raising questions regarding the role of norepinephrine system in depressive symptoms.

Norepinephrine selective reuptake inhibitors are selective of the norepinephrine synaptic transporter (NET): reboxetine, atomoxetine and desipramine have a Ki value of 1.1, 5.8 and 7.4 nM respectively for the NET, compared to 130, 1451 and 163 nM respectively for the serotonin transporter (SERT). Even if this selectivity is high at the transporter site, reboxetine may activate the serotonergic neurons in the dorsal raphe nucleus. Thus, through inhibition of norepinephrine reuptake, reboxetine promote activation of a2-adrenergic receptors on those serotoninergic neurons, responsible for an increase in their firing rate and serotonergic release in the rat prefrontal cortex and hippocampus (1) . Accordingly, the functional response to NRIs should not be norepinephrine restrictive.

Some studies have focused on the role of serotonin in the behavioral effects of NRIs. In different mice models of serotonin depletion treated with desipramine or reboxetine, no changes in the animal behaviour have been observed as compared to control littermate. So, evidence for a role of serotonin in the clinical effects of NRIs remains unclear.

In summary, the molecular selectivity of NRIs at the reuptake site does not only lead to a modulation of norepinephrine system, but certainly influences serotonergic pathways.

Similarly, the well-documented selectivity of SSRIs at serotonin uptake site is not necessarily reflected at the functional or clinical levels, suggesting that other neurotransmitter could be secondarily affected by these drugs. These observations highlight the difficulty to predict the therapeutic profile of antidepressants on the sole basis of their presumed mechanism of action. Here we report a case of reported exposure to Baclofen toxicity and a subsequent withdrawal state. This occured in a 45 year old patient suffering from progressive spastic quadriparesis of unknown origin, on oral Baclofen, with no previous psychiatric diagnosis, who following elective insertion of an intrathecal Baclofen pump (ITB) went from a comatose state to a fulminant psychotic episode. During the planned elective intrathecal surgical insertion of the Baclofen pump, the patient was inadvertently given a twenty times higher than usual daily dose as a result of which she became progressively drowsy and unresponsive (GCS 3). The pump was promptly stopped and within 24 hours she regained consciousness but developed vivid visual, auditory and tactile hallucinations. She was found to experience intensive feelings of derealisation and depersonalisation and appeared to have developed a complex paranoid delusional system. On assessment she also reported Schneiderian first rank symptoms but interestingly, otherwise appeared cognitively intact, fully orientated throughout and with retained attention. A withdrawal reaction was diagnosed and Baclofen reintroduced. Although the patient's mental state improved following the reestablishment of Baclofen, the elaborate delusional ideation and feelings of depersonalisation continued prompting introduction of Risperidone 1 mg nocte. Over the following days further improvement was noted and eventually Risperidone was stopped. Once discharged, the patient was followed in the psychiatric outpatient clinic where she continued to report some altered perceptions but no psychotic symptoms during the next few months. In conclusion, ITB therapy is increasingly used to treat medically intractable spasticity. There needs to be a greater awareness of the dangers of Baclofen toxicity and withdrawal including its neuropsychiatric effects. Of interest, Baclofen is a well known GABA B receptor agonist. In recent studies of rodent models activation of GABA B receptors with Baclofen it was reported to reverse sensory gating deficits (1), a known endophenotype of psychosis. The pathophysiology of the effect of Baclofen in humans in producing psychotic symptoms during withdrawal states, such as were present in our patient, is as of yet unclear but warrants further investigation. Introduction: Women have a higher prevalence of major depressive disorders (MDD) than men. However, there is an ongoing controversy about whether men and women respond equally well to antidepressant medications. Some studies suggested that allelic variation of the serotonin transporter genelinked polymorphic region (5-HTTLPR: long (L) or short (S)) could influence emotions in males and females in opposite directions. L allele has also been associated with higher antidepressant response but some replications found contradictory results. We assessed the potential role of Gender x Genotype interactions to explain these conflicting results.

Aim: The purpose of the present study was to explore the extent to which gender modulates antidepressant response and its possible interaction with 5-HTTLPR polymorphism.

Patients and Methods: In a naturalistic prospective open study, 106 inpatients (77 women and 29 men) with DSM-IV MDD, completed a 4-week treatment period. The severity of depression was assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at baseline and after 4 weeks treatment; 5-HTTLPR genotype was determined by PCR and Genescan analysis, independently from clinical assessment.

Results: Even when controlling for higher scores at baseline (p<0.01), women had a higher response rate than men (p<0.05). A Gender x Initial Severity interaction was shown for antidepressant response, which decreased with increasing initial severity in women, while increased with initial severity in men (p<0.05). A trend towards Gender x Genotype interaction was also shown (p=0.08): Lallele tended to be associated with a greater response in women and a lower response in men.

Conclusion: Even if lacking statistical power, our results show gender differences in antidepressant response and suggest that 5-HTTLPR L allele may be one pathway that activates different responses to antidepressant in females than in males. Continuing research is needed to determine how gender influences response to antidepressant treatment in MDD.

OLANZAPINE PLASMA CONCENTRATION AND ANTIMANIC RESPONSE-PRELIMINARY RESULTS FROM AN OPEN LABEL, LONGITUDINAL MULTICENTER TRIAL Denizot H. 1 , Libert F. 2 , Blanc O. 1 , Bourdel N. 3 , Dubray C. 4 , Schwan R. 5 , Llorca P.M. Service de Psychiatrie B, Laboratoire de Pharmacologie et de Toxicologie, 3 Unité Inserm UMR 384, 4 Unité Inserm CIC 501, Clermont-Ferrand; 5 CHU Nancy, Service de Psychiatrie, Nancy, France Introduction: Olanzapine is an atypical antipsychotic that is effective in the treatment of acute mania. Olanzapine plasma concentration ‡ 23, 2 ng/ml have been identified as a predictor of clinical response in acutely ill patients with schizophrenia.

Aim: To determinate the relation between plasma concentration of olanzapine in a sample of inpatients or outpatients with acute mania.

Patients and Methods: Open label, longitudinal, multicenter trial including patients with acute mania and treated with olanzapine for 6 weeks; dosage of olanzapine was adjusted according to clinical response and plasma concentration of olanzapine was measured at 3 and 6 weeks by high-performance liquid chromatography (HPLC). Clinical status was assessed by Young Mania Rating Scale (Y-MRS) and Clinical Global Impression (CGI). Patients were considered ''responsive'' if they showed at least a 50% reduction in Y-MRS score and a CGI Severity scale score of £ 3.

Results: We include twelve patients (6 men and 6 women), mean age 57.4 yr. The mean olanzapine dosage was 11.46 mg/day (SD=2.49) at the same dosage for 16.8 days (SD=6.5) .

Receiver operating characteristic (ROC) curve analysis at 3 weeks determined a plasma threshold (above which a better clinical response was obtained) to be 15, 9 ng/ml. There was no correlation between the daily dosage of olanzapine and the plasma level (p< 0.05).

Olanzapine plasma levels were not significantly different between responders (n=6) and non responders (n=6) at 3 weeks.

Conclusion: Our threshold is lower than those reported in schizophrenia. This may be related to lower dosage used in treatment in mania than in schizophrenia and particularly to the small number of our sample and the large variability between patients of the olanzapine plasma levels. Because this study did include a small number of patients, further research on this specific issue is urgently needed. Djerada Z., Hamadache H., Houery M., Niel P. Hôpital Paul Guiraud, Laboratoire de Biologie Polyvalente, Villejuif, France Introduction: Therapeutic indice of lithium is narrow, so laboratory suggests drug monitoring.

Aims: Look for pharmacokinetic interactions (PKI) between lithium and associated treatments in psychiatry. We calculate normal range of Concentration/Dose (NRC/D) which will permit, despite variable posologies, to see PKI and non-compliance.

Patients and Methods: Plasmatic dosages were done by selective-electrode NOVA for 52 patients (sex ratio1) average age 40 years during 12 months. Treatments were collected.

Interactions analysis was done according to previous studies 1 . Therapeutic Range 1 (TL) are respectively for prolonged/immediate release galenic forms between 0.5 -0.8 mmol/L/0.6-1.20 mmol/l. For the calculation of the ratio C/D, we selected patients with normal renal function (NA+/K+/creatinine/TR after steady-state 1 ) without PKI.

Results: Despite the recommendations 2 , only 166 lithium dosages were done during 12 months, for 52 patients out of 68 (76%) treated with lithium. We find 35 plasmatic values below the TR in 26 (50%) patients. Among them, 12 had 15 values below relapse level (0.3 mmol/l) 1 . 12 values were beyond TR for 10 patients (20%) of which 6 (11%) were above the toxic level (> 1.5 mmol/l) 1 . Inadequate dosage was the main reason, and the compliance was confirmed by nursing. We did not find PKI for any of the patients, however pharmacodynamic interactions were observed; 57 associations with neuroleptics, 7 with antiepileptics and 6 with antedepressant-SSRI. 27 patients were selected to calculate the average, standard deviation and variation coefficient of C/D. Values were (n = 79) m=0.036 +/)0.028 l )1 with CV=40% for both galenic forms. We observe in 7 cases that the association with laxatives diminishes C/D by 44%.

Conclusion: Inadequate dosages are the main reason for lithium levels out of the TR for 30 % of the cases. This orientates our information for the doctors for a better dosage adaptation.

The calculation of C/D will allow us to better detect the PKI and the non compliance.

We suspect an interaction between laxatives and lithium; more studies are necessary to confirm these results. Introduction: Considering the co-administration in psychiatry, our laboratory proposes a therapeutic drug monitoring of clozapine (TDMC).

Aim: Display the importance of the TDMC and the impact of PKI, and studying the relationship between the ratio Concentration/ Dose (C/D), outside the normal values (0,6 -1,2) 1 , and the occurrence of PKI or non-compliance.

Patients and Methods: Serum concentrations of clozapine (SCC) (therapeutic range (TR) 350-600 lg/l) 1 were determined by HPLC-UV for 48 refractory schizophrenics (16 females, 32 males, mean age 42 years) during 15 months. The PKI analyses were established on reviews 1 .

Results: Despite international recommendations 2 , only 340 SCC were measured during 15 months, on 48 patients out of 72 (67%) treated by clozapine. More than 59% measures outside the TR, 20% were toxic or lower than the relapse threshold (RTh= 200 lg/l) 3 . 101 SCC on 25 (53%) patients, were below TR. Among these 25 patients, 9 had 29 out of 83 SCC below the RTh. These last are explained by PKI: 5 associations with tobacco, 3 with Omeprazol, 3 with Valproic acid, 1 with Carbamazepine and three cases of non-compliance.

101 SCC over TR have been observed on 26 subjects (54%), including 14 who presented at least one toxic SCC (>900 lg/l) 1,2 . These last are explained by PKI: 13 pulmonary bacterial infections, 1 smoking cessation, 10 associations with Valproic acid, 3 with Antipsychotics, 2 with Fluoroquinolones, 2 with antedepresseur-SSRI, and 1 with oral contraceptive.

Individuals sensitivity/specificity of the pharmacokinetic parameter C/D outside the Normal values are respectively, 67%/94 % and 80%/83% for the minimal and maximal values of TR,.81%/77 % for the presence of enzymatic inhibitors, 50%/55 % for the presence of enzymatic activator, finally the sensitivity of C/D below 0.6 for the non-compliance is 100%.

Conclusion: The TDM is justified in more than half of the dosings. It has also been shown that 90% of extremes values (200-900 lg/l) were explained by PKI. Moreover, our studies have allowed us to prove that C/D can be used to predict PKI and especially non-compliance. Introduction: Methadone is currently used as substitution for illegal opiates. The recommended oral daily dose of methadone is 40 to 60 mg which are administered as a racemic mixture. In humans, the Renantiomer is 50 times more active than the S-enantiomer.

Concentrations over 250 ng/ml and 400 ng/ml for the R-enantiomer and the racemic mixture, respectively, are most often required to stabilize maintenance treatments.

Aim: The objective of this work was to evaluate the impact of therapeutic drug monitoring (TDM) on the treatment of patients with clinical disorders, signs of withdrawal or side-effects related with methadone therapy. This drug monitoring was performed in order to correlate R-methadone plasma concentrations with dose and pharmacological effects.

Patients and Methods: Fifty-three hospitalized patients were followed by the addictology department of a French University Hospital. The study was conducted over two years and included 128 dosages by chiral liquid chromatography (1 to 9 dosages/patient, mean: 2.4) .

Results: Mean prescribed doses ranged from 15 to 180 mg/day (70 ± 43 mg/day). Seventy-four percent of the results were out of range, over or under 250 ng/ml for the R-enantiomer.

There was no correlation between the daily dose and the plasma concentration: 64% of the patients with maintenance doses between 60 and 120 mg/day were out of the therapeutic range. Plasma concentrations over or under therapeutic range were found in cannabis or other illicit drug consumers cannabis mainly, tobacco smokers, alcohol addicts (29%). Insufficient (20%) or excessive (3%) prescribed doses were also identified. Lack of observance was notified in 23% of these patients. In most of cases (75%), the initial dose of methadone was modified in order to reach TDM goals.

Conclusion: In conclusion, TDM of R-methadone can be useful in methadone maintenance therapy follow up as plasma concentrations are not correlated to daily doses. However, clinical evaluation remains fundamental, especially in multi-drug addicts who require lower therapeutic doses. TDM may also be used when poor adherence to treatment is suspected. Introduction: The dopaminergic (DA) and the vulnerability/stress models of schizophrenia postulate an over DA activation in stress condition in schizophrenia. Indeed, it has been reported that the increase in plasma HVA (a DA metabolite) measured after a 2DG challenge (a metabolic stressor) was significantly stronger in patients than in controls.

Aim: The aim of this study was to compare in a double blind sham controlled cross over study, elevations of plasmatic HVA levels after a 2DG challenge in 10 patients with schizophrenia, 10 of their unaffected siblings and 9 frequency matched controls.

Results: We reported a significant intermediate 2DG-induced plasma HVA peak increase (mean ± SEM ng/mL) in siblings (+4.45 ± 1.5) compared with patients and (+8.95 ± 1.7) and with controls (+3.61 ± 1.2) . Additionally, we reported a significant 2DG-induced increase in 5HIAA (a serotonin metabolite) levels between groups. The increase in plasma 5HIAA in siblings (+4.64 ± 1.2) was higher than in patients (+1.78 ± 0.5) and than in controls (+1.84 ± 0.6). No significant difference was observed between patients and controls. Introduction: Long-term stability of schizophrenic syndromes constitutes an important challenge, notably in a therapeutic point of view and long-term studies of anhedonia, one of the main negative symptoms, are rare.

Aim: The present study was to explore the stability of anhedonia and its relationships with schizophrenic symptoms across a 13-year study period. We test the hypothesis that trait anhedonia, rated by the Physical Anhedonia Scale (PAS), is stable and independent of schizophrenic symptoms across this period, while measures of state anhedonia are not.

Methods: 150 Schizophrenic subjects were evaluated at two points in time; at admission to a hospitalization, and 13 years later. Trait anhedonia was assessed using the Chapman physical anhedonia scale, while state anhedonia was assessed with a subscale extracted from the Beck Depression Inventory. The Positive and Negative Syndrome Scale (PANSS) was used to rate schizophrenic symptomatology.

Results: Based on results from multiple regressions, negative and depressive dimensions were significant predictors of state anhedonia. Trait anhedonia was not associated with negative symptoms, but was associated with severity of disorganization symptoms and with state anhedonia. Following effective treatment, the relationship between trait anhedonia and disorganization symptoms decreased, while state anhedonia continued to a be a significant associate of trait anhedonia. Importantly, in the current study, state and trait anhedonia were found to be linked, but depressive symptoms in general were not associated with physical anhedonia.

Conclusions: The results indicated that trait anhedonia, in contrast to state anhedonia, had absolute stability, was independent of the negative dimension of schizophrenic symptomatology and partially linked to depressive anhedonia. that P300 potential amplitude in an auditory paradigm is marginally attenuated in first degree relatives of Schizophrenic patients in e. g. siblings (e.g. Turetsky et al. 2000) . We investigated in healthy volunteers whether Event Related Oscillations are more appropriate to characterize deficits in information processing than the amplitude measures. In relation to the NMDA hypothesis, research on ketamine effects has been carried out and will be presented. They will be compared to the effects of apomorphine and preliminary data on the interaction with neuroleptics. Moreover evaluations of the biomarker obtioned in parents of patients will be shared with the audience. We hope so to develop deepened thoughts on the P300 endophenotype. We recently identified time resolution as measured by simultaneity perception to be a basic cognitive function implicated in some schizophrenias 3 . We re-analyzed our data concerning a group of 38 patients after classifying them according the three families of Leonhard. As a comparison, we also tested the three DSM4R categories of schizophrenia, schizo-affective depressive and schizoaffective bipolar, chosen because of their prognostic implications.

Our results show that time resolution is different among Leonhard diagnostic families (F1,69 = 4.8, p = 0.004) but not among the current DSM4R diagnostic groups (F1,65 = 2.4, p = 0.07). Systematic schizophrenia (n = 10) demonstrated significantly poorer time resolution relative to the non-systematic group (n = 13) (p = 0.02). Cycloid psychosis (n = 15) only tended to differ from the nonsystematic group (p = 0.09). Both cycloid psychosis and systematic schizophrenic patients had significantly poorer time resolution relative to controls (n = 35) (all p < 0.02), whereas those of the nonsystematic group were similar. Accordingly, in this sample, patients who better fit to a neuro-developmental disorder (cycloid psychosis and systematic schizophrenia), appeared distinct relative to the groups that better fit to an hereditary disease (non-systematic schizophrenia). Thus Leonhard's empirical and clinically oriented diagnosis differ according to this basic cognitive function.

Introduction: Switching between antipsychotics is common practice when patients experience efficacy and/or tolerability issues. Few studies have investigated different switching strategies.

Aim: To evaluate safety, tolerability, effectiveness and impact on social cognition of a titrated-versus fixed-dose switching strategy from risperidone to aripiprazole in a general practice setting.

Methods: This 12-week, multicentre, open-label study included patients with schizophrenia (DSM-IV-TR) experiencing insufficient efficacy and/or safety/tolerability issues while receiving risperidone for ‡6 weeks. Patients were randomized to titrated-or fixed-dose switching regimens.

Primary endpoint was the proportion of patients who discontinued due to adverse events (AEs) at Week 12. Secondary end- Results: Discontinuations due to AEs were similar between titrated-and fixed-dose strategies (3.5% vs. 5.0%; p=0.448 ). Titratedand fixed-dose groups showed improvements (Week 12) in mean PANSS Total scores ()14.8 vs. )17.2; LOCF), mean CGI-I scores (2.9 vs. 2.8; p=0.425 ; LOCF), ASEX scores ()1.5 vs. )1.9 from baseline; OC) and serum prolactin levels ()48.7 vs. )48.5 from baseline; OC). The POM scores indicated a preference for aripiprazole compared with risperidone using either regimen. SWN scores showed improvement from baseline in both groups (titrated-dose, +8.6; fixed-dose, +10.3; p=0.223 ; OC). Both switching strategies showed improvements (titrated-dose vs. fixed-dose; Week 12; LOCF) in social cognition as indicated by decreased GEOPTE patient ()5.3 vs. )6.1), caregiver () 5.4 vs. ) 9.9 ) and Index scores ()5.1 vs. ) 9.8) .

Conclusion: Switching to aripiprazole from risperidone can be effectively and safely achieved in a general practice setting, with beneficial effects on social cognition and physical functioning, through a slow down-titration of risperidone and either a titratedor fixed-dose switching strategy for aripiprazole. Following Hardy-Baylé's proposal, setting communication disorders as a central and specific deficit in schizophrenia 1 , two new tools for the evaluation of (1) communication disorders [2] [3] and (2) intentional reading 4 have been developed in our team. We have previously demonstrated that both instruments separate significantly schizophrenic patients from normal controls and depressed patients [3] [4] .

Aim: The present study aims at demonstrating, on a large number of schizophrenic patients, the validity and utility of these two scales for the clinical quantitative evaluation of schizophrenic patients.

Patients and Methods: The study was part of a pharmacological trail assessing a large number of patients (n=206; age mean=41 .3 SD=10.49 ) with different clinical scales (PANSS, BPRS) and measurements of social cognition (SCD * , V-SIR * ).

Results: The mean value and the range previously reported on smaller groups are confirmed (SCD mean=7.49 SD=4.11; V-SIR mean=24.36 SD=8.00). Results from both scales demonstrate a normal distribution. Intrinsic qualities will be described (Alpha Cronbach SCD= 0.88; V-SIR=0.76). The use of these two tools for the assessment of patients in a large scale multi-centric pharmacological essay indicate that feasibility and transferability of expertise for testing are very good. Scores from these two tests were significantly correlated.

V-SIR scores do not correlate with BPRS scores. Interestingly, only few individual items of the BPRS and the PANSS correlate significantly (p>.05) with ToM scores (SCD scores: 6 out of the 18 items of the BPRS and 17 out of 30 PANSS scores correlate with SCD scores; V-SIR scores: only one out of the 18 items of the BPRS and six out of 30 PANSS items correlate with the V-SIR scores).

Conclusion: Evaluation of severity in schizophrenia needs quantitative assessments of communication and ToM disorders. We aimed to demonstrate here, for the SCD and for the V-SIR, the feasibility and utility of their use in a comprehensive battery for clinical and cognitive evaluation in Schizophrenia. English versions of these two scales are now being validated within English-speaking normal and pathological groups. Poor compliance is a major concern. It depends on the treatment, the patient, the patient's environment, the physician and the illness. In schizophrenia, a low level of insight (i.e., awareness of the disorder) is thought to weaken compliance, but the link is not well-established. Our aim was to study the relations between compliance, insight and therapeutic alliance in a population of patients with schizophrenia and schizoaffective disorder, and to identify clinical and sociodemographic risk factors responsible for poor compliance. We used the self-scored MARS (Medication Adherence Rating Scale) to measure compliance, the SUMD (Scale to assess Unawareness of Mental Disorder) to measure insight, and a specific self-questionnaire to measure therapeutic alliance. Our results confirm that low insight and a weak therapeutic alliance are correlated to poor compliance. The gravity of the illness, the severity of the overall disability and addictive disorders are also liable to weaken compliance.

Compliance, insight, therapeutic alliance and these risk factors should be assessed regularly.

The scales used in our study may provide a useful support. The development of psychoeducational programmes targeting patient insight and information could improve compliance in schizophrenia treatment. Further work is needed in this area.

Introduction and Aim: Patients with schizophrenia are impaired in the fluent execution of action sequences. But, the fluent sequencing of action requires timing of the different elements of the sequence as well as the integration of the information pertaining to time and force. The aim here was to assess whether these deficits might be due to a problem in the timing of action, or rather in the more complex problem of integrating information from multiple sources.

Patients and Methods: A rhythm production task was used in a group of patients with schizophrenia (N= 10) and pair matched controls. The subjects' task was to squeeze a load cell in its centre in order to produce force pulses that were synchronised with each tone, that were presented with equal time intervals (600 ms) or alternating time intervals (400/800ms), with either equal force levels (12N) or alternating force (8N/16N). To assess the influence on performance of self versus external pacing, each trial was constituted of a 12s period of synchronisation followed by a 24s period of continuation. Results: These preliminary results suggest that schizophrenia is characterised by a timing deficit. Time intervals are shortened, hence, patients accelerate and this is especially observed when subjects are to act upon an internal representation of the rhythm to produce (i.e. during continuation). Results were similar for equal and alternating force levels.

Conclusion: These findings suggest that fluency problems in schizophrenia are not a problem in integration but rather a problem in the timing of multiple elements of a sequence. It would be interesting in future studies to investigate the role of dopamine as it is known to play an important role in the control of the internal clock.

We report here the case of a hospitalized 11-year-old child (YP), with a positive diagnosis of very early onset schizophrenia. YP experienced verbal auditory hallucinations, a delusion of alien control and hetero aggressive behavior. Antipsychotic drugs were unsuccessful and furthermore, provoked severe acute dystonia. We present here YP's functional MRI scan during auditory verbal hallucinations (Fig.1) .

Methods and Results: Ten sessions of fMRI-guided, low frequency (1 Hz), repeated trans-cranial magnetic stimulation (rTMS) over the right temporo-parietal cortex, were successful in improving YP's sense of agency ( Fig.3) but not the auditory hallucinations. Thus, a second series of rTMS was run over the left temporoparietal cortex. This was successful in improving both YP's sense of agency and stopping the verbal auditory hallucinations.

Conclusion: To our knowledge, this is the first published case demonstrating the efficacy of fMRI-guided rTMS in the treatment of verbal auditory hallucinations in a child with early onset schizophrenia. Both the subjective ratings (Children's Global Assessment Scale) and the objective cognitive improvements remained stable 5 weeks after each rTMS session. Introduction: Sleep regulation is closely associated to HPA activity. Alterations in both systems may be precursors of psychiatric dis-orders like depression even at an early stage of development, i.e. in children (1) . So far the impact of microstructure in sleep regulation like sleep spindles is unknown. In recent studies, sleep spindles have been linked to efficient cortical-subcortical connectivity and cognitive abilities especially during neurodevelopment.

Aim: Sleep spindles in kindergarten children were analyzed and related to sleep regulation and HPA axis functioning.

Patients and Methods: Nine five-year old kindergarten children were enrolled in a cross-sectional examination of HPA system activity assessed by saliva cortisol measurements (morning cortisol after awakening) and sleep regulation investigated by sleep EEGmonitoring. Sleep EEG spindles were visually scored and were put into relation to macrostructural sleep and HPA activity parameters.

Results: Sleep spindles were correlated to basal morning cortisol secretion (AUC basal) (curvilinear r = .83, p = .01), though were negatively correlated to cortisol increase (AUC netto) after awakening (r = -.77, p < .05). Though not statistically significant but by trend, spindle density (i.e. number of spindles per hour of stage 2sleep) is negatively correlated to REM density (r = -.57, p = .11), as increase of awakening cortisol was associated to REM density by trend (r = .63, p = .07).

Conclusion: Not only sleep continuation parameters as reported before (2) but also sleep microstructure reflected by sleep spindles may be associated to sleep regulation and HPA system functioning. The results are discussed within the frame of the extended twoprocess-model of sleep regulation. Objective: Many overweight adolescents display elevated risk for the development of eating disorders, also experience elevated levels of negative affect, impairment in health-related quality of life, and eating disturbances, although prospective data are needed to determine the directionality between eating disorder pathology and general psychopathology. Body dissatisfaction is commonplace for teenage girls and is associated with dieting and unhealthy weightcontrol behaviours. The idealisation and pursuit of thinness are seen as the main drivers of body dissatisfaction, with the media prominent in setting thin body ideals. Multiple impulsive behaviours are common in adolescent's eating disorders, and multiimpulsive patients appear to do more poorly in treatment. However, comparatively little is known about the origins of multi-impulsivity in such cases. History of childhood trauma was associated with a higher number of impulsive behaviours and with the presence of multi-impulsivity.

Childhood sexual abuse was particularly important, and was associated with self-cutting, alcohol abuse, and substance abuse (amphetamines, cocaine, cannabis and 'other substances', including ketamine and benzodiazepines. Childhood trauma and comorbid psychopathology in anorexia nervosa. Adolescent delinquents appear to have a different experience of negative emotions than comparison adolescents and to have low incidence for eating disorders. The experience of emotions appears to differ in state and trait conditions. These emotions may be related to childhood experiences of trauma. To evaluate the role of mirtazapine in the treatment of anorexia nervosa in adolescents.

Data Sources: There are not data in the literature regarding mirtazapine use in adolescents with diagnosis of Anorexia nervosa. Ten females and four males patients suffering from AN restricting subtype (DSM-IV TR criteria) were admitted to a closed ward (Day Hospital Service) and treated with mirtazapine for twenty four weeks receiving 5 mg intravenous mirtazapine on day baseline; 15 mg intravenous mirtazapine on day 2 and 3; and 30 mg oral mirtazapine per day from day 4 up to the end of the study (day 180). Besides weekly determination of clinical parameters (Body Mass Index [BMI], Hamilton Depression Rating Scale [21-HAMD], Hamilton Anxiety Rating Scale [HAMA], Sleep Disorders Questionnaire -SDQ) were measured before treatment (day -1), at the beginning of treatment (baseline), after 1 week (day 7), and after 4 weeks (day 28) and after 8 weeks (day 56) and to the end of the study (day 180) with mirtazapine treatment.

Results: Mirtazapine use increased in BMI was seen (p=0.002). Subjects with sleeping difficulties reported an improvement sleep quality.

Conclusion/Discussion: Preliminary evidence supports the use of mirtazapine for treatment of anorexia nervosa in adolescents by demonstrating that mirtazapine 15-30 mg daily promotes weight gain and has positive effects on associated psychological symptoms.

Limitations of the reported data include small sample size. Studies with larger sample sizes are necessary to establish its role in therapy. Introduction: The war is a process in which people try to solve accumulated antagonisms by using the available power with a vast use of armed violence. The war in Bosnia and Herzegovina, from 1991 till 1995 is 14.534th in the human history, and in all of them about 3 billion and 643 million people were killed, of which 21%, i.e. 765 . 030 .000 were children (Arnautovic, 2000) .

Methods: The children of the 2nd, 3rd, 4th and 5th grade of elementary school from the region of the town Banja Luka in Bosnia&Herzegovina, who were born from 1989 to 1992, and who, in their early pre-school age, went through various war situations. At the time of the formal end of the war, in November 1995, the oldest of them were six years old. The investigation was carried out during 2000/1. The sample consisted of the children of the E and the C groups. The E group comprised the children who had experienced a number of ''difficult'' war situations, while the C group consisted of the children who did not experience any such situation, they were only exposed to slight effects of a general nature, characteristic of environments outside the war action zones (the relatives coming as refugees, a short stay in the shelter, changes in food, life without electricity, a longer staying at home, and alike). In that way, a sample was formed of 428 children, 214 of the E group (120 boys and 94 girls) and 214 of the C group (120 boys and 94 girls). The children with mental retardation, sensory disorders or the bilingual children were not taken into consideration.

Result: According analyses of results of frequency appearance of stuttering in E group was 18 (8,41%) and in C group was 10 (4,67%); in E group the frequency of articulation disorders was 51 (28,83%) and C group 49 (22,90%); in E group the frequency of dysgraphy was 28,04% and C group 17,76%; frequency of dysorthograpia in E group was 33 (15,42%) and C group 19 (8,88%) and summary frequency of speech and language disorders in E group is166 (77,57%) and C group 120 (56,07%).

Conclusion: Research pointed that there is immediate need, after life danger is stopped, for making conditions for preventive acting and following, discovering and giving advisory and direct logopedics help.

FREQUENCY OF DEVELOPMENTAL DYSGRAPHY AFTER BOMBING Golubovic S. Faculty of Special Education and Rehabilitation, University of Belgrade, Belgrade, Serbia Introduction: Developmental dysgraphia, according to Golubovic, S.(1998 Golubovic, S.( , 2000 Golubovic, S.( , 2003 Golubovic, S.( , 2005 Golubovic, S.( , 2006 is poor writing abilities in spite of adequate intelligence and in the absence of a sensory disorder or neuropsychological signs. A few children with dysgraphy lack only the fine-motor coordination to produce legible handwriting, but some may have a physical tremor that interferes with writing. In most cases several brain systems interact to produce dysgraphy.

Methodology: We examined 306 children of young school age, I, II, III, IV grade of primary school, 173 male and 133 female, with goal of confirming fluency in appearance of dysgraphy. With test for searching dysgraphy of handwriting, The Scale for the Assessment of the Handwriting Dysgraphy (Ajuriaguerra & Auzias, 1971) consists of taking handwriting samples in the three forms of writing: dictation, a free composition and rewriting. The texts of the dictation and rewriting were identical and contained all the letters of the Cyrillic alphabet, while the free composition was titled: ''An Experience of Mine''. The dysgraphy of the handwriting has been assessed on the basis of the sum of the points obtained, whereby the handwritings have been classified into 4 categories: the handwriting without dysgraphic elements (0-9.5 points), dysgraphic handwriting (14-18.5 points), exceptionally dysgraphic handwriting (19 points and more).

Results: The biggest frequency in appearance of dysgraphy is 46,7%, mainly graphomotoric, in children of I grade whose intrauterine development was during bombing in 1999 year, after comes II grade-33,8%, and III, IV grade-20%, while characteristics of bad hand writing had 19%, and harmonious handwriting had 52,6%. Children of I grade are significantly unsuccessful in relation with children of same age in previous generations. It is confirmed that fluency in appearance of dysgraphy in children of younger school age in this school is significantly bigger, in relation with frequency of dysgraphy which confirmed in earlier searches.

Conclusion: Derived results show that fluency of appearance of dysgraphy in total sample is 28%, and in boys 35%, while in girls is 18,8%. Many children with dysgraphy are extremely slow in their writing performances.

THE WAR CONDITIONS AND THEIR CONSEQUENCES Salic J. 1 , Golubovic S. 2 1 Center for Education and Rehabilitation Hearing and Speech, Banja Luka, Bosnia & Hercegovina; 2 Faculty of Special Education and Rehabilitation, University of Belgrade, Belgrade, Serbia Introduction: The war conditions and their consequences, which represent the most frequent experience of the children of the sample under investigation are: refuge and separation; life of the children in the zones of the battle and their exposure to the explosions of bombs, shells, mines and alike; death and/or the child's attendance to deaths, massacres, tortures or seeing the dead bodies of their closest relatives, missing or imprisonment of the closest relatives; the children who personally experienced maltreatment and intimidation and/or were present during maltreatment and intimidation of close persons; physical wounding of the child or his/her close persons, the children who suffered burns or longer freezing, the children who suffered longer or more frequent hunger; living in refugee camps.

Method: The corpus was formed on the basis of answers of parents surveyed through a questionnaire covering 17 war situations that their children had been through. The experimental (E) group (214) included children who had been through a few ''difficult'' war activities and situations, and the control (C) group (214) included those children who had been through situations typical of environments outside the war activities zone.

Results: In this study 146 (68,22%) of the children in the E group lived in the zones of the battle (from a few months up to 2 and 5 years) and 124 children (57.94%) who were exposed to the explosions of bombs, shells, mines and alike. In the sample studied, out of 214 children of the E group, the killing of the closest relatives experienced 132 children (61.68%), and that: the killing of the father 78 children (59.09%), the death of other closest members of the family -51 (38.64%) the killing of the mother 2 children, and the killing of both parents one child.

Conclusion: Research pointed that there is immediate need, after life danger is stopped, for making conditions for preventive acting and following, discovering and giving advisory and direct psychological and logopedic help. Introduction: In attempting to ''even the playing field'' in competitive sports, the World Anti-Doping Code (WADC) bans specific performance enhancing medications. 1 This might create novel discrimination against medically ill competitors. To avoid such inequities, therapeutic use exemptions (TUE) are utilized in special circumstances (medical necessity with no alternative treatment available). One such situation involves psychostimulants, used to treat ADD/ADHD, which are prohibited in-competition. 1 Worldwide ADHD pooled prevalence is 5.3%, ranging from Middle East's 2.4%, Europe's 4.6%, North America's 6.3%, to South America's 11.8%, with prevalence in boys 10.1%, girls 4.1%, children 6.5%, and adolescents 2.7%. 2 No prevalence studies have been done with gymnasts. At gymnastic meets, parents volunteered the existence of ADHD or treatment for ADHD features.

Aim: To address preliminary findings regarding ADD/ADHD in a boys' gymnastic team, implications for further studies with proposed research survey questionnaire to measure prevalence of ADD/ADHD with behavioral effects of gymnastics, and ethical considerations.

Method: Analysis of ADD/ADHD prevalence in a boys' gymnastic team from informal interview with literature review.

Results: By parent report, >50% of gymnasts in a boys' gymnastic team were noted to have been diagnosed with ADD/ ADHD in the past and/or to have been treated with a psycho-stimulant. Parents commented that gymnastics served as ''behavioral therapy'' in controlling ADHD symptoms and that this effect carried into the classroom. Only one parent was cognizant of WADC in-competition ban for psychostimulants and need for TUE.

Conclusion: ADD/ADHD prevalence is reported in a surprisingly large proportion of gymnasts in a boys' gymnastic team. Detailed survey of a larger number of gymnasts of both genders is required to verify the high prevalence of ADD/ADHD in this population and behavioral effects of gymnastics noted in this one team. A proposed research survey questionnaire to measure both prevalence of ADD/ADHD and behavioral effects of gymnastics is presented. Introduction: Morningness is a stable characteristic of individuals, related to impulsivity and novelty seeking. The evening orientation is a risk factor for psychiatric conditions such as depression and personality disorders. Attention-Deficit/Hyperactivity Disorder (ADHD) affects 4% in adults but remains under-diagnosed. We hypothesized that adults suspected of having ADHD are more evening oriented than adults without ADHD.

Method: The Composite Scale of Morningness (CSM) is a measure of morningness with 3 factors: Activity Planning (F1), Morning Affect (F2) and Time of Rising (F3). The Adult Self-Report Scale (ASRS) is a self-reported questionnaire devised to facilitate the screening of ADHD in primary care settings. It is part of the World Health Organization Composite International Diagnostic Interview (WHO-CIDI). The 18 items are written to reflect the DSM-IV diagnostic criteria for ADHD. Subjects were students from a large university in Paris (France) and parents of children referred to a specialized consultation in Nice (France) for ADHD. Three hundred and twelve subjects completed the ASRS (98 males, 31.4%), and among them one hundred and eighty four subjects completed the CSM (38 males, 20.7%).

Exploratory factor analyses with oblique rotation were performed on the polychoric correlation matrices of the full ASRS and the CSM.

Results: All three CSM factors correlated negatively with ASRS Inattention factor (F2), none with ASRS Impulsivity/Hyperactivity factor (F1).

Conclusion: Inattention is more strongly related to eveningness than Impulsivity/Hyperactivity is and, therefore, eveningness may constitute an endophenotype of the predominantly inattentive subtype of ADHD in adults. Introduction: In Europe, the potential consequences of the increasing use of psychoactive substances by pregnant women are a major public health concern. Alcohol and substance use (tobacco, cannabis, cocaine...) prevalence during pregnancy remains under estimated.

Consumption of one or more psychoactive substances during pregnancy may have serious consequences on child development. In France, the prevalence of alcohol and drug use during pregnancy remains poorly studied.

Aim: The objectives of this study were: (1) to assess the prevalence of alcohol, tobacco, cannabis, and cocaine consumption during pregnancy (2) to improve our knowledge of sociodemographic characteristics of tobacco, alcohol and substance users during pregnancy.

Patients and Methods: An epidemiological observational multicenter study was carried out in the three main maternities hospitals in Haute Normandie (France). Every pregnant woman leaving in Haute Normandie who gave birth to a living child and who agreed to participate in the study was included. Mothers were evaluated from Day 1 to Day 3 after childbirth using the Addiction Severity Index (ASI) in order to assess the frequency (during the last month) and the severity of alcohol, tobacco and substance use.

Results: One hundred and ninety three were eligible for this study. Three refused to participate in this study and in three cases the interview was not fully completed. Among the 187 women who were included: 23% (n= ) were smokers. None declared to use regularly alcohol, 5.5% only occasionally. None declared to use cannabis or other psychoactive substances.

Concerning the fathers, according to women's interviews: 39.5 % were smokers. 6 .8% were drinking alcohol regularly and 38% occasionally. 4% were using cannabis regularly. None was using other psychoactive drug.

Conclusion: According to the prevalence of tobacco use in the general population, tobacco use was adequately reported during mothers' interview. In contrast, alcohol and drug use were under estimated by the interviews, this study emphasizes the need for alcohol and drug use biological markers in this population. Objective: Alcohol-dependence is a complex multifactorial disease. Identify predictors of outcome is an important stake for better treatment matching. Severity, age, gender, marital status and psychiatric comorbidities are often reported as predictor of relapse. Our objective was to identify and compare predictors of detoxification.

Method: The study concerns a sample of 122 DSM IV alcohol dependent patients (83% of men) enrolled by their usual GPs. Standardized questionnaires collected clinical and social data on each visit during a prospective follow-up lasting 18 months. GPs had any obligation in management. Analysis was conducted using Cox's regression for each potential factor such as socio-demographic characteristic, clinical or life events, factor linked to the management.

Results: 43% of patients attempted at least one detoxification during 18 months of follow-up.

Results concerned 875 visits. Severity of alcohol-dependence [RR 1.17] , gender and life events [RR 1.48 ] predicted detoxification whereas depression [RR 0.26 ] and somatic problems [RR 0.24] limited it. Frequency of the visits (addressing alcohol consumption [RR 1.73] ) and co-management by a psychiatrist [RR 1.76] or other specialists lead to detoxification. Benzodiazepines were the only medication linked to detoxification [RR 1.81 ] but sustained prescription was related to relapse [RR 3.15] .

Conclusions: Besides patient's characteristics, quantitative management by the GP appears to predict better outcome in alcohol-dependence. Simple warning and non-structured advice by untrained GPs, repeated in close consultation, could increase detoxification. The role of life events and the role of other practitioners confirm also the importance of a medico-psycho-social management in alcohol dependence. Introduction: Most clinicians agree to judge the impact of cannabis use as minor in opioid dependent patients. Nevertheless, cannabis dependence may be a risk factor for a poorer outcome.

Patients and Methods: We measured cannabis use, abuse and dependence and lifetime psychiatric disorders in a sample of hospitalised French opioid dependent subjects, mainly poly-drug users. Patients were evaluated using structured interviews, allowing DSM IV diagnoses of current abuse or dependence to every substance, and current or past psychiatric disorders. The variables of poor outcome were: dependence on others substances, use of IV route, lifetime DSM IV psychiatric diagnoses. The association between cannabis abuse and dependence and the variables of poor outcome were tested with khi 2 tests. Due to the number of tests performed, significance level was chosen at p = . 005 .

Results: Here we show the results of the first 66 patients analysed. Cannabis use was found in 75.8% of patients and cannabis dependence in 30. 3% . Cannabis use and cannabis dependence were not found to be associated with more alcohol, sedatives, cocaine, crack, heroin dependence and were also not associated with the use of IV route. Cannabis dependence, but not cannabis use, was associated with more lifetime psychotic symptoms (p = .002).

Conclusion: Cannabis use regarded the majority (75.8%) of opioid dependent patients evaluated in hospital setting. Although the sample was small, cannabis dependence was found to be associated with lifetime psychotic symptoms. Cannabis dependence should be evaluated and psychotic symptoms searched in order to provide these patients with help in quitting cannabis and/or antipsychotic medication. Introduction: Lateralisation investigation evaluates the efficiency of connective fibres describing the advantage of one brain hemisphere over the other. The result of this is the description of the lateralisation index as the indicator of cognitive skill, covering the range of -100 for the total advantage of the right hemisphere to 100 for the left hemisphere. Despite the fact that the physiological pattern was confirmed a long time ago (1, 2) , it is still an intriguing fact whether lateralisation potential correlates with other indicators. It is well known that this indicator is not constant. It is different in left and right hand individuals, it may also undergo certain modifications; it changes, for example, in musicians (3) or in sleep deprived individuals (4) . Certain changes are also quite probable to take place with age, expressing diminishing of the intellectual potential.

Aim: The aim of the study was showing the correlation between the value of the lateralisation index value and the cognitive skill. Additionally, the values describing the number of wrong answers or absence of answers from each of the studied groups were taken into account.

Patients and Methods: The study encompassed 160 individuals (72 women and 88 men) in 4 groups counting 40 individuals, each. All subjects were right -handed, confirmed by proper tests. D1, K1 and K2 groups had 21 men each and 19 women, D2 group 25 and 15 respectively. D1 and D2 groups were constituted by patients hospitalized due to Unipolar and Bipolar Disorder. According to Hamilton's scale the intensification of depression was average, 22,3 and 22,7 for each of the groups. The remaining K1 and K2 groups were healthy individuals, not burdened in their family with psychic illnesses. The difference between K1 and K2 groups depends on the fact that K1 group was only constituted by the students of the first year of the medical course.

Results: High value of lateralisation indicator correlates with high level of cognitive skill. It is visible both in K1 and K2 groups and with D1 and D2. Similar dependences may be noticed in the absence of the answer range, however such a correlation is missing in the answers with an error.

Conclusion: Lateralisation index may be considered as the indicator of the cognitive skill.

The lateralisation index decrease is quite probable with age and the natural decrease of intellectual ability.

RISK REDUCTION IN A 57 YEAR OLD SCHIZOPHRENIC SMOKER WITH KLEPTOMANIA Kieffer P., Wirth N., Martinet Y., Kahn J.P., Schwan R. Dept. of Psychiatry, CHU Nancy, France Tobacco use is a major public health problem in Europe. Both prevalence and types of tobacco use vary from one country to another according to Tobacco Control policies. In France the 1 st February 2007 decree set out the Government's strategy for tackling smoking in France. Tobacco free areas were installed in all public zones including hospitals. Cigarette smoking is more frequent among psychiatric patients with a smoking prevalence among those with schizophrenia 2 to 3 times higher than in the general population. If quitting smoking for these patients is more difficult, in contrary to a common view, these patients are as motivated to quit smoking and try to quit as often as non-psychiatric smokers. Their greater difficulty in quitting smoking is, as least in part, due to their higher level of tobacco addiction, and to their lower confidence in their ability to quit smoking. Until recently, most physicians considered a smoking cessation as almost impossible for these patients. Consequently, these patients experience earlier smoking related morbidity and mortality. Indeed, ischemic heart disease is the first cause of death among patients with schizophrenia, and this high rate of smoking, results in a 20 % reduction of their life expectancy. In respect to patients with schizophrenia, the usual smoking cessation programmes (nicotine replacement therapy, bupropion, varenicline …) may not be efficient and appropriate. Specific smoking cessation programs have been developed but most of the evaluated programs included only younger non deficient subjects. To our knowledge no study has evaluated smoking cessation in older patients with chronic deficient schizophrenia. In this case report, we will describe the smoking cessation in a 57 year old man with chronic deficient schizophrenia, kleptomania and nicotine depen-dence. It will be shown that cigarette smoking should not be considered ''as normal'' for patients with deficient schizophrenia. Encouraging them to quit smoking, treating them, and supporting their efforts, should be almost ''mandatory''. For smokers unable or unwilling to quit, harm reduction can be proposed as an alternative.

Rengade C.E., Lambert H., Senninger J.L., Schwan R. CHU Nancy, Pôle des Spécialités Médicales 1, Service de Psychiatrie, Hôpital Jeanne d'Arc, Toul, France Background: 5 to 49% of the patients undergoing M.M.T. consume alcohol. They show less willingness and are less involved in the maintenance program. They have to stick longer to it and their observance is weaker. Alcohol misuse is the main cause for their increased mortality ad morbidity rate. Several reasons for alcoholic relapse have been identified among alcohol addicts, such as alexithymia for a start; 40,8% of drug addicts seem to be suffering from that ''difficulty to identify one's feelings and to tell them from physical sensations''. Besides, self-esteem may be weaker in alcoholics and drug addicts than in sample population. Eventually, several studies on temperament have underlined the connection between some emotions or features of temper -such as selfdirectedness-and alcohol dependence. However such a connection has never been established for methadone patients depending both on opiates and on alcohol.

Objectives: We aim at defining the influence of alexithymia, selfesteem and temperament on the consumption of alcohol of methadone patients.

Methods: We conduced a multivariate, prospective and openlabel study, including two groups of methadone patients; the first one suffering from alcohol misuse according to the criteria of the Alcohol Use Disorder Test; the second one being abstinent. In the process we complete Bagby's Toronto Alexithymia Scale (TAS-20), together with Coopersmith's Self-Esteem Inventory and Eysenck's Temperament and Character Inventory (revised version by Cloninger).

Results and Conclusion: Our study includes 100 patients, 57% of which are typical alcohol misusers. After comparing the alcohol dependent group and the abstinent one we notice among the first higher rates of alexithymia, a weaker self-esteem -particularly in the social and family sphere -and lower scores of self-directedness and persistency. The significant positive correlations between the various tests allow us to assert strong connections between alexithymia, self-esteem and temperament. We will discuss our results in the light of the data available in the literature.

Caci H. 1 , Bouchez J. 2 , Baylé F.J. 3 1 Service de Pédiatrie, Hôpital Archet 2, Nice ; 2 Clinique 'Liberté', Substance Abuse Dept., Bagneux; 3 Université Paris-Descarte, Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne IN-SERM U796, Paris, France Introduction: Impulsivity is involved in many psychiatric disorders. But with regard of the construct definition or its measurement, the discussion remains open. The Barratt Impulsiveness Scale (BIS-11) is extensively used worldwide in psychiatry and psychology research. Unlike the original concept of a one-dimensional construct, it proposes a three-subtrait structure of impulsiveness (namely cognitive, motor and non planning) that has been operationalised in recent versions of this instrument. The difficulties in different studies to clearly identify cognitive impulsiveness subtrait originally conceptualized lead to a new label as an antinational factor. The BIS is a 30item self-report instrument with overlapping items and items with weak intercorrelations. The aim of the study was to validate a short form of the BIS-11 with as few as 5 items for each substraits.

Method: An expert panel classified items in three lists with regard of their content (cognitive/attentional, motor, non-planning).

Students from a large university in Paris (France) served as subjects and filled out the BIS-11. Only completed questionnaires were analyzed (n=1639 subjects, including 965 female, 58%). Polychoric correlation matrices of the three lists of items were analyzed using both exploratory factor analyses and confirmatory factor analyses on two randomly-created independent subgroups.

Results: We were able to identify three 5-item unidimensional factors. Gender differences are reduced when the two subgroups are pooled.

Conclusion: The BIS short form has an improved reliability and supports the three-subtrait structure of impulsiveness postulated by Barrat. It may be a useful instrument to further assess cross-cultural differences in the measurement of impulsivity. Aim: The aim of our study is to investigate QOL and QOL's psychological determinants of patients with TS aged of 16 years or older. Since the QOL assessment included self-rating questionnaires, a pilot study was necessary.

Patients and Methods: In the final study, a total of 372 members of the French Association of GTS will receive 4 questionnaires: the GTS-related symptoms questionnaire, the WHOQOL-26 (World Health Organization Quality Of Life), the FSQ (Functional Status Questionnaire) and the SCL-90 (self-rating questionnaire about psychiatric symptoms).

Results: The feasibility study included 17 patients who fulfilled DSM-IV criteria for GTS, referred to a specialized unit in an university hospital. The mean time to complete them was: 31.5 ± 10.2 minutes. Fifteen of 17 patients had completed and returned the questionnaires: 10 were perfectly completed, one was unusable due to a lot of invalid answers and 4 had only one answer missing which didn't invalidate the assessment. The questionnaires did not seem lengthy or cumbersome. Thus questionnaires were easily completed by subjects.

Conclusion: Some adjustments were realized to make questionnaires more readable. The final study started in March 2007, 169 members returned our questionnaire. Detailed final study methodology and statistical analyses will be presented later.

B12 DEFICIENCY IN CAPGRAS SYNDROME: A CASE REPORT Yalug I. 1 , Kirmizi-Alsan E. 1 , Ozdemir S. 2 1 Kocaeli University Medical Faculty, Dept. of Psychiatry, Kocaeli; 2 Istanbul University, Cerrahpasa Medical Faculty, Dept. of Psychiatry, Istanbul, Turkey Introduction: Capgras Syndrome (CS) is a rare delusional misidentification syndrome which is characterized by the belief that a significant other has been replaced by an identical-looking imposter. It is usually seen in schizophrenia or dementia; however some organic etiologies such as B12 deficiency, migraine, hashimoto thyroiditis, drugs (adrenaline, atropine methonitrate, morphine) and AIDS related pneumocystis pneumonia were identified.

Aim: We present a CS case with a diagnosis of delusional disorder and an underlying B12 deficiency.

Patients and Methods: 32-year-old male patient was brought to our emergency psychiatry department after assaulting his mother with a penetrating object. He was claiming that his wife, child and mother had been kidnapped and replaced by identical impostors. He had deliberately assaulted her mother in an attempt to test whether she was his real mother or not. He was diagnosed with schizophrenia seven years ago; however he was unresponsive to antipsychotic treatments, even to clozapine. He was medication free on admission.

Results: Physical and neurological examinations didn't reveal any pathology. Laboratory findings such as blood chemistry, complete blood count, folic acid, ECG, EEG, PA Lung X-ray and cranial CT were in normal limits, but vitamin B12 level was found to be low. The patient hospitalized in psychiatric ward and treated with I.M. B12 injections and 30 mg/d aripiprazole. The severity of the delusional misidentification decreased and the patient gained insight towards his condition during the 30 day clinical follow up at the hospital. The psychiatric examination revealed a complete remission of the CS on discharge. The final diagnosis was delusional disorder (axis I) and B12 deficiency (axis III). The patient was not diagnosed with schizophrenia because the diagnostic criteria for schizophrenia, were not met apart from the delusions which were seen to decrease dramatically by the pharmacological treatment.

Conclusion: To our knowledge, this is the second CS case report with B12 deficiency in literature. The fact that the patient has received antipsychotic medication and B12 replacement therapy simultaneously makes it difficult to isolate the organic cause in terms of etiology. Nevertheless, it can be suggested that the alleviation of a potential organic etiology, that is the B12 deficiency through replacement therapy, could be the reason behind the significant improvement in the patient's symptoms which had not been achieved by previous treatment attempts.

Introduction: Ekbom Syndrome (ES) or Delusional Parasitosis is a rare and not widely known monosymptomatic psychosis in which the patient has a delusion of being infested with parasites. The patient has the belief that insects, worms or other small pests live in his/her body and feed on it. Visual or tactile hallucinations that are consistent with the thought content can accompany the delusions. It is typically observed with females over the age of 50.

With some patients, an underlying physical disorder such as hypertension, heart failure, hypoparathyroidism, Huntington's chorea and Alzheimer's disease can be detected.

Aim: To present an elderly patient, who was diagnosed with ES, concomitant with hyperthyroidism and achieved remission with combination of pimozide and propylthiouracil.

Patients and Methods: A 70 year-old female patient was previously hospitalized in endocrinology ward with the complaints of weight loss, tremor, sweating, palpitations, intolerance to heat and fatigue, and was diagnosed with hyperthyroidism. During the hospital stay, increased speech and the feeling of large worms going around in her body were added onto her initial complaints. Haloperidole was started additionally to antithyroid medications in psychiatric consultation and the psychiatric symptoms of the patient decreased in time. 2 weeks after discharge, her somatic delusions were relapsed. She was hospitalized in a psychiatric inpatients clinic with the complaints of feeling flat worms which were moving all over her body and accumulating in her stomach.

Results: The patient was diagnosed with ES, concomitant with hyperthyroidism. Her treatment was initiated with pimozide 2mg/ day and titrated up to 4mg/day. The patient was followed up for a month without any antithyroid medication based on the endocrinology consultation, during which an increase in thyroid hormone levels was observed.

Propylthiouracil, an antithyroid agent was started and as the thyroid levels dropped, the movement of the tape worms began to slow down. It was observed that her somatic delusions appeared and/or the severity of the delusions increased in parallel with the increases in the thyroid hormone levels. When the psychiatric symptoms disappeared completely, she was discharged from the hospital and followed up at the outpatient setting. She remained in euthyroid state and her psychiatric symptoms were never observed again until now.

Conclusion: Researchers have pointed out to the relationship between ES and physical diseases. It has been reported that there has been 80-90% improvement in somatic delusions with pimozide treatment. In our case, pimozide along with antithyroid medication alleviated the patient's symptoms. Multidisciplinary approach is necessary for a successful treatment in disorders such as ES.

However, there seems to be room for improvement as a number of suggestions were formulated to support these pathways of drug information.

PSYCHIATRIC SYMPTOMS AFTER BILATERAL SUBTHALAMIC NUCLEUS STIMULATION IN PARKINSON'S DISEASE Bourgognan F., Barroche G., Lefebure I., Colnat-Coulbois S., Kahn J.P., Schwan R. CHU Nancy, Dept. Psychiatrie, Hôpital Jeanne d'Arc, Toul, France Background: Stimulation of the subthalamic nucleus (STN) is currently recognized as the treatment of choice for severe levodoparesponsive forms of Parkinson's disease (PD). This technique improves parkinsonian motor disability; levodopa induced dyskinesias and permits a reduction in the doses of antiparkinsonian medication. However, the treatment may result in psychiatric complications which are most often precocious and transient.

Objective: The objective was to investigate, in patients with advanced PD, the occurrence of psychiatric disorders after bilateral STN stimulation.

Methods: We conducted, in CHU de Nancy, a six-month prospective open-label study.

Patients were assessed before and after surgery by using open interviews and psychiatric scales: mini international neuropsychiatric inventory (MINI), apathy scale of Starkstein, social adjustment scale (SAS-SR) and also others psychiatric scales if a psychiatric disorder was present (MADRS, MAS, HAMA).

Results: Eight consecutive patients (6 men, 2 women) were included in this study. Several kinds of problems were observed after surgery: two cases of apathy, one subject show emotional reactivity, one patient developed agoraphobia and one patient fall in depression. In addition, social adjustment did not improve in all patients, even when was observed a marked improvement in parkinsonian motor disability. In this study, psychosocial factors appear to be allimportant.

Conclusion: A multidisciplinary approach should be taken to patient care, not only after surgery but also before. Notably, a preoperative psychosocial preparation could contribute to ameliorate patients' social adaptation after surgery.

Lack of impact of repetitive High Frequency Transcranial Magnetic Stimulation on mood in healthy female subjects

The biological affects: a typology

rTMS studies of mood and emotion. Electroencephalogr

Neurological soft-signs and minor physical anomalies in schizophrenia: differential transmission within families

Validation of the French version of CAARMS in a psychiatric outpatient clinic for emerging psychological disorders

Validation an factorial structure of a standardized neurological examination assessing neurological soft-signs in schizophrenia

Adult psychosis, common childhood infections and neurological soft signs in a national birth cohort

Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition American Psychiatric Association

Psychological theories of depression: potential application for the prevention of acute coronary syndrome recurrence

Time-related predictors of suicide in major affective disorder

Association between depressive symptoms and mortality in medical inpatients

L'anhédonie en psychiatrie: revue

Frequency of symptoms in Melancholia (Depressive Illness)

Treatment resistant depression in an Australian context II: Outcome of a series of patients

The Hamilton Depression Rating Scale: Has the gold standard become a lead weight?

Responses to cancer diagnosis and treatment: posttraumatic stress and posttraumatic growth

Psychological interventions for distress in cancer patients: a review of reviews

Prevalence of acute and post-traumatic stress disorder and comorbid mental disorders in breast cancer patients during primary cancer care: a prospective study

Neuroendocrine interaction In: Psychopharmacology, The fourth generation of progress

Interrelationships among anxiety, aggression, impulsivity, and mood: A serotonergically linked cluster? Psychiatry Research

Neurobiology of emotion perception II: Implications for major psychiatric disorders

Unmasking disease-specific cerebral blood flow: Mood challenge in patients with remitted unipolar depression

18F]MPPF as a tool for the in vivo imaging of 5-HT1A receptors in animal and human brain

Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with

Serotonin type-1A receptor imaging in depression

Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior

Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment

Ü ber die Mischzustände des manisch-depressiven Irreseins

The Mirror-Neuron System

Depression in cancer patients: a critical review

Depression and cancer: mechanisms and disease progression

Distinct Profiles of Neurocognitive Function in Unmedicated Unipolar Depression and Bipolar II Depression

Choroby afektywne'' w: ''Psychiatria'' red. Bilikiewicz A., Strzy_ zewski W. PZWL Warszawa; 1992: s

Lateralized auditory processing in depression: dichotic click detection

The International Classification of Sleep Disorders 2°ed

Daily rTMS improves in mood depression

TMS in the treatment of depression

Has rTMS treatment for depression improved? A systematic review and meta-analysis comparing the recent vs the earlier rTMS studies

TMS Studies: Examination of the Reliability of ''Standard'' Coil Positioning by Neuronavigation

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

Extrinsic connections of the basal ganglia

Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology

Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder

Does the chimpanzee have a theory of mind?

Self and self-directed rules

Theory of mind'' in schizophrenia: a review of the literature

The cognitive neuropsychology of schizophrenia

Organisation de l'action, phénomènes de conscience et représentation mentale de l'action chez des schizophrènes

Single indicator of risk for schizophrenia: Probable fact or likely myth?

Theory of mind and its relation to schizotypy

Scales for physical and social anhedonia

Decisions in conditional situation and theory of mind in schizotypy

Schizophrenia, symptomatology and social inference: investigating ''theory of

Emotion recognition via facial expression and affective prosody in schizophrenia: a methodological review

Early-stage visual processing deficits in schizophrenia. Current Opinion in Psychiatry

Dr Angry and Mr. Smile: when categorization flexibly modifies the perception of faces in rapid visual presentation

Conscious, preconscious, and subliminal processing: a testable taxonomy

The neural correlates of conscious vision

Neurophysiologic mechanisms of attention: a selective review of early information processing in schizophrenics

The serotonin syndrome

Serotonin syndrome in the elderly after antidepressant monotherapy

References 1. Selective noradrenaline reuptake inhibition enhances serotonergic neuronal activity and transmitter release in the rat forebrain

Jia Zhou 3. The role of noradrenaline and selective noradrenaline reuptake inhibition in depression

Gender-specific differences in depression and treatment response

Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene

2002 -The course of anhedonia during 10 years of schizophrenic illness

Modèle quadridimensionnel des schizophrénies chroniques issu de la structure factorielle de l'échelle des syndromes positif et négatif (PANSS). Étude chez un groupe de 153 schizophrènes chroniques et comparaison avec la structure factorielle de la BPRS. Encéphale, XXIII

Is anhedonia a specific dimension in chronic schizophrenia?

Classification of endogenous psychoses and their differentiated etiology, Second, revised and enlarged edition

Big bang nosographique: la classification des psychoses endogènes de Karl Leonhardsynopsis et revue des travaux

Low time resolution in schizophrenia Lengthened windows of simultaneity for visual, auditory and bimodal stimuli

PATIENTS WITH SCHIZOPHRENIA WITH INSUFFICIENT EFFICACY/TOLERABILITY ON RISPERIDONE

Dillenschneider A. 3 , Hanssens L. 4 , Sieglinde M. 5 , Kerselaers W. 6

Dommartin les Toul; 3 Bristol-Myers Squibb Company, Rueil-Malmaison, France; 4 Bristol-Myers Squibb Company

PsychRes. (in revision) *SCD: Scale of the assessment of communication disorders

Versailles Situational Intentional Reading References

Efficiency of grip force adjustment for impulsive loading

Voluntary movement dysfunction in schizophrenics

A disturbance in the control of muscle force in neuroleptic-naive schizophrenics patients

Abnormal Sequencing of motor actions in patients with schizophrenia: evidence from grip force adjustments during object manipulation

Deficient motor synchrony in schizophrenic disorders: clinical correlates

Time estimation in schizophrenics. Perceptual and motor skills

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Hypothalamic-pituitary-adrenocortical (HPA) activity in kindergarten children: Importance of gender and associations with behavioural/ emotional difficulties

Electroencephalographic sleep profiles and hypothalamic-pituitary-adrenocortical (HPA)-activity in kindergarten children: Early indication of poor sleep quality associated with increased cortisol secretion

Institut za istrazivanje zlocina protiv covecnosti i medjunarodnog prava

Uticaj neposrednih ratnih dejstava na pojavu govorno-jezickih poremecaja. Magistarska teza, Defektoloski fakultet

Delachau-x et Niestle. L'eciture de l'enfant

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Disleksija/Dyslexia

Dysgraphia in the children of primary school. 7. Congress of the European Federation of Neurological Societies

Disgrafije kod dece mladjeg skolskog uzrasta. U Golubovc, S., i grupa autora: Smetnje u razvoju kod dece mladjeg skolskog uzrasta. Defektoloski fakultet

Razvojni jezicki poremecaji / Developmental language disorders

USADA Guide to Prohibited Substances and Prohibited Methods of Doping

The worldwide prevalence of

Speech representation in an unbiased sample of left -handers

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Laterality. Functional asymmetry in the intact brain

Dichotic listening and sleep deprivation: vigilance effects

References 1. Garden G. Physical examination in psychiatric practice. Advances in Psychiatric Treatment

Is there a stethoscope in the house (and is it used)? Arch Gen Psychiatry

The psychiatric physical examination

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A neuropsychological analysis of Capgras Syndrome

Delusional parasitosis or Ekbom's syndrome

Delusional parasitosis: a dermatologic, psychiatric and pharmacologic approach

Author Index

Introduction: Cognitive deficits have been described in patients during major depressive episode. Several studies show that depressed people have difficulties in being specific in autobiographical memory. However, due to methodological and conceptual issues, little attention has been paid to episodic autobiographical memory in depression.Aim: The present study investigated the specificity of autobiographical memories among twenty-eight depressed patients; the relationship between autobiographical memory, depression and quality of life. Alternatively, we also evaluated the effect -on autobiographical memory -of antidepressant therapy ((clomipramine (150 mg / day) or venlafaxine (150 mg / day)) in acute depressed patients.Patients and Methods: During an episode of major depression and after remission (J0, J4, J32-46, J74) we investigate 28 patients compared with 28 normal volunteer controls. Among patients 14 patients were treated with clomipramine (150 mg/day) and 14 patients with venlafaxine (150 mg/day). Efficacy variables included the 21-item Hamilton Depression Rating Scale (HAM-D 21 ) total score, HAM-D 21 depressed mood item score, scores on the Montgomery Å sberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity of Illness (CGI-S) and Improvement (CGI-I) scales, and rates of response (based on change from baseline HAM-D or MADRS score or CGI-I score). Quality of life was assessed with the Beth Israel/UCLA Functional Status Questionnaire (FSQ). We used neurocognitive tests (Della Salla autobiographical memory interview, the Dritschel's autobiographical fluency task, a free recall task, Digit Symbol Substitution Test, visual analogical scale, Semantic Verbal Fluency test) exploring attention, implicit, anterograde, retrograde memory and an autobiographical memory test.Results: Our preliminary findings confirm a negative effect of depression on autobiographical memory with a significant but incomplete improvement after remission. The effects and differences between clomipramine (150 mg / day) and venlafaxine (150 mg / day) will be presented and their implication in clinical practice will be discussed.Conclusion: Improvement in depression is associated with decrement of depressive symptoms but also with cognitive improvements. Our results will be presented and their implication in clinical practice will be discussed. Prospective studies are warranted to study the effects of potential differences among antidepressant therapies on long-term cognitive outcomes in depression. Modern biological psychiatry should probably also emphasize on the relevance of physical symptoms and signs during care management [1] . Psychiatric physicians probably face a new era where integrative medical practice will become the rule.

Aim: The aim of the study was to identify the degree of importance and the performance of physical examination in clinical psychiatric practice in Belgium.Methods: We sent questionnaires to 250 psychiatrists and psychiatry residents about stethoscope use, clinical attitude to physical symptoms and signs and about interpretation of para-clinical routine examinations. Furthermore we asked for the degree of importance regarding physical examination and whether the present situation should change. The results were stratified and correlations with sex, age and main activity (stationary/in-patients or ambulatory/out-patients) were carried out.Results: We report the preliminary results of 105 responders (response rate 42%, mean age 43.7 years, 63 males). 36.2% used their stethoscope and 22.9% performed standard neurological examination during clinical activity of the last 7 days. 20% reported that a physical symptom or sign changed their diagnostic or treatment attitude during the last day.Psychiatrists treating mostly in-patients performed more physical examinations but there was no significant difference between academic and non-academic hospitals. Younger male psychiatrists tend to perform more often physical examination than any other group.Nevertheless the majority of all interviewed psychiatric physicians attributed a high degree of importance to physical health in their patients and agreed that the actual situation regarding the positioning and the management of physical health in daily psychiatric practice should change or improve.Conclusion: The topic whether psychiatrists should somewhat get physically closer to their patients from time to time is always hotly debated since the beginnings of our speciality as a whole [2, 3] . It is striking that despite recent efforts in several countries to improve the skills of psychiatrists in this area of clinical practice, the literature reporting the actual state of the art is extremely rare and poor [1] [2] [3] .Financial Support: Daniel Neu is supported by a research grant from the National Funding for Scientific Research from the Ministry of Research, Culture and Superior Education of the Grand-Duchy of Luxembourg. Introduction: Informing patients on their medicines is a patient right. What does current information provision on antidepressants to patients admitted to a psychiatric hospital look like? What is the current practice of health care professionals? What are the experiences of patients?

Aim: This study aims to explore current practice on drug information provision on antidepressants in psychiatric hospitals from the point of view of health care professionals as well as patients with a depression.Patients and Methods: A qualitative study in eight Flemish psychiatric hospitals consisting of semi-structured interviews with separate interview guides for health care professionals and for patients. Interviews were tape recorded, verbatim transcribed and analyzed using NVivo7.Results: Interviews with 9 patients and 34 health care professionals were performed and analyzed.Patients get information on antidepressants, firstly, through psychiatrists and, secondly, through nurses. Hospital pharmacists have a supporting role.The approach in giving information depends on patient characteristics and his/her mental state. Information is provided mainly orally. Leaflets are not frequently distributed. Patients also get information on antidepressants during psycho-educational sessions. On request, patients can read a package insert under supervision of a health care professional.Health care professionals pay attention to non-verbal cues of patients to verify if information has been understood. Information is repeated when the first instruction was not clear for patients. Patients as well as health care professionals are satisfied with current practice on information provision. Health care professionals reported lack of time and lack of interdisciplinary contacts as negative aspects. Patients indicated that health care professionals take too little initiative to give information about medicines. Positive aspects reported by health care professionals are the hospitals' openness and the opportunity for patients to ask questions to psychiatrists as well as nurses. Suggestions for improving practice are: providing more medication information to patients, in particular on side-effects; enhancing the availability of easy readable information; and organizing continuing education for nurses on medicines.Conclusion: Patients are informed about their antidepressants through various pathways.