key: cord-1037474-k3ovm43p
authors: Palladini, M.; Mazza, M.G.; Rovere-Querini, P.; Benedetti, F.
title: P.0691 Mood-congruent cognitive distortion and processing bias in depressed covid-19 survivors: a comparison with major depressive disorder
date: 2021-12-30
journal: Eur Neuropsychopharmacol
DOI: 10.1016/j.euroneuro.2021.10.651
sha: 580f61a3f2c57c303870363f8b5bc408bd44d1e3
doc_id: 1037474
cord_uid: k3ovm43p

Introduction. COVID-19 survivors often experience psychiatric sequelae, with depressive psychopathology as the leading cause for needing psychiatric intervention [1]. Depressive cognitive distortion is a core feature of major depression, fostering the experience of negative emotions and hampering recovery [2]. Moreover, cognitive biases are well-documented in patients with inflammatory diseases and associated depressive symptomatology [3]. Considering both the high prevalence of clinical depression among COVID-19 survivors and the critical role of cognitive distortions in depression, we consider of crucial importance to investigate cognitive processing biases in COVID-19 survivors. Methods. We studied 729 participants, divided in three groups: (1) 362 COVID-19 survivors;(2) 73 inpatients with Major Depressive Disorder (MDD);(3) 294 healthy participants (HC). Severity of depression was self-rated on the Zung Self-Rating Depression Scale (ZSDS). Neuropsychological bias toward emotional stimuli and the general negative outlook on the self were tested in a self-description task [4], during which subjects were asked to self-attribute or refuse positive and negative morally tuned adjectives, and latencies and frequencies of attribution were recorded. Depressive dysfunctional attitudes in causal attribution and interpretation of hypothetical events were measured on the Cognition Questionnaire (CQ). We performed homogeneity of slope or separate slopes analysis when appropriate in the context of Generalized linear model (GLMZ), with an identity link function. Likelihood ratio test was computed as a measure of significance for tested effects and Akaike Information Criterion (AIC) was obtained as goodness of fit measure [5]. Results. 22.4% COVID survivors self-rated their depressive symptoms above the clinical threshold. Bias in speed of information processing significantly predicts self-description in all groups (COVID depressed: Wald W2=19.81;COVID non depressed: W2=15.48;MD: W2=13.65;HC: W2=33.54;all p<0.001). Information processing bias and frequencies of attribution of morally negative elements strongly predicted the severity of self-rated depressive psychopathology (ZSDS scores) (Processing bias: LR χ2=40.99, p<0.0001;Frequencies: LR χ2=127.89, p<0.0001). Additionally, the cognitive distortion in causal attribution and interpretation of hypothetical events (CQ scores) in depressed post-COVID patients showed intermediate levels of severity in all dimensions between non-depressed post-COVID patients, and MDD (post-hoc Fisher's least significance test: p<0.05 at all comparisons). Moreover, the CQ total score significantly influenced the ZSDS scores (χ2=84.60, p<0.0001). Interestingly, homogeneity of slope analysis revealed regression slopes were parallel in COVID-depressed and hospitalized MD patient groups in all models, yielding no significant group interaction. Finally, bias in information processing and negative self-description both predicted CQ scores (Latencies ratio: χ2=3.91, p=0.0479;Frequencies: χ2=42.96, p<0.0001). Conclusions. The breadth of moral self-reproach and the severity of cognitive distortion in evaluating events showed the same association with severity of depression in MDD and in post-COVID depressed patients, distributing along a gradient of severity, thus suggesting that these individual features of depressive cognitive distortion are shared in these conditions and should be addressed as treatment targets in depressed COVID-19 survivors. No conflict of interest

Background : Depression has been ranking as one of the leading causes of disability from 1990 throughout 2017, showing the absence of progress in adequate treatment [1] . Increasing evidence exists that inflammatory factors play an important role in the pathogenesis of depression. A consequence of inflammation appears to be the deceleration of adult neurogenesis [2] . In a rodent model neurons were chronically exposed to bacterial lipopolysacccharides (LPS) as a model for chronic inflammation. In these animals the dendritic length of immature new-born granule cells in the hippocampus was reduced [3] . How human neurons react to inflammatory processes is, however, not entirely clear. This is in part due to the limited availability of human neurons. Human circulating monocytes have pluripotent capacities. Bellon et al. (2018) showed that they can be transdifferentiated into neuronal-like cells in only 20 days. This method is minimally invasive, fast and allows individualized examinations on a cellular level [4] . In our study we will assess three questions: Firstly, if there is a difference in dendritic growth in neuronal-like cells in different groups of patients. Secondly, if the cell morphology differs in an inflammatory environment in different disease conditions. And lastly, if there are differences in expression of inflammation-relevant proteins of interest. Our hypothesis is that dendritic growth is attenuated in patients with depression, in particular in patients with high peripheral inflammatory markers. Furthermore, neurogenesis might be inhibited in an inflammatory surrounding and expression of inflammatory proteins might differ between the groups. Methods : We aim to recruit 10 patients with depression of whom 5 have elevated peripheral inflammatory markers (CRP, IL6) and 5 do not. As a comparison, we include 5 patients with schizophrenia and 5 healthy controls. Fresh blood is obtained from patients and healthy controls and within 24 hours we separate peripheral blood mononuclear cells (PBMCs) by Ficoll-Paque. Thereafter, CD14 + cells are isolated using the magnetic separation protocol by Milenyi biotec. We then transdifferentiate cells into neuronal-like cells. At day 20 we treat one group of the cells with LPS and polyinosinic:polycytidilic acid to model respective inflammatory surroundings. At day 21 cells are fixed and differentiation is measured by morphology, specifically arborisation. The cells are stained using MAP2 and Rbfox1 antibodies. The supernatant of the cells is collected for protein analysis. Finally, we perform cell lysis and protein extraction on one group of the samples on day 22. Results and expected outcome : Recruitment of patients started in May 2021 and is ongoing. Preliminary results will be presented. Conclusion: With our study we hope to contribute to a better understanding of the connection between depression and inflammation. Our cell model might offer the possibility to examine inflammatory processes in individual patients on a cellular level. Furthermore, it could be possible to study the reaction of neuronal-like cells to different treatment options. depression, fostering the experience of negative emotions and hampering recovery [2] . Moreover, cognitive biases are well-documented in patients with inflammatory diseases and associated depressive symptomatology [3] . Considering both the high prevalence of clinical depression among COVID-19 survivors and the critical role of cognitive distortions in depression, we consider of crucial importance to investigate cognitive processing biases in COVID-19 survivors. Methods. We studied 729 participants, divided in three groups: (1) 362 COVID-19 survivors; (2) 73 inpatients with Major Depressive Disorder (MDD); (3) 294 healthy participants (HC). Severity of depression was self-rated on the Zung Self-Rating Depression Scale (ZSDS). Neuropsychological bias toward emotional stimuli and the general negative outlook on the self were tested in a self-description task [4] , during which subjects were asked to self-attribute or refuse positive and negative morally tuned adjectives, and latencies and frequencies of attribution were recorded. Depressive dysfunctional attitudes in causal attribution and interpretation of hypothetical events were measured on the Cognition Questionnaire (CQ). We performed homogeneity of slope or separate slopes analysis when appropriate in the context of Generalized linear model (GLMZ), with an identity link function. Likelihood ratio test was computed as a measure of significance for tested effects and Akaike Information Criterion (AIC) was obtained as goodness of fit measure [5] . . Moreover, the CQ total score significantly influenced the ZSDS scores ( χ 2 = 84.60, p < 0.0001). Interestingly, homogeneity of slope analysis revealed regression slopes were parallel in COVID-depressed and hospitalized MD patient groups in all models, yielding no significant group interaction. Finally, bias in information processing and negative self-description both predicted CQ scores (Latencies ratio: χ 2 = 3.91, p = 0.0479; Frequencies: χ 2 = 42.96, p < 0.0001).

Conclusions. The breadth of moral self-reproach and the severity of cognitive distortion in evaluating events showed the same association with severity of depression in MDD and in post-COVID depressed patients, distributing along a gradient of severity, thus suggesting that these individual features of depressive cognitive distortion are shared in these conditions and should be addressed as treatment targets in depressed COVID-19 survivors.

Background: Starting treatment with an oral contraceptive (OC) has been associated with an increased risk of a subsequent depressive episode [1] . This might be related to OCs effect on the serotonergic brain system as suggested by recent cross-sectional data from our group which show that healthy OC users relative to non-users have lower cerebral serotonin 4 receptor (5-HT 4 R) levels as measured with Positron Emission Tomography (PET) [2] . This may be linked to a depressive state at least in some individuals and, intriguingly, may be critical for antidepressant drug treatment outcome [3] . Aims: The primary aim is to determine if regional brain 5-HT 4 R non-displaceable binding potentials (BP ND ) measured by [ 11 C]-SB207145 PET differs between OC users and nonusers among women with an untreated depressive episode. The secondary aim is to evaluate if baseline regional 5-HT4R BP ND before treatment start is associated with treatment outcome in a manner dependent on OC status. Methods: [ 11 C]-SB207145 PET imaging data from the Neu-roPharm 1 Study [4] were available from 56 premenopausal women with a depressive episode, of which 23 used OCs. Treatment outcome after starting on escitalopram (or duloxetine due to switch at week 4 or later) was measured by relative change in the Hamilton Depression Rating Scale 6 items (r HAMD 6 ) from baseline to week 8. The association

COVID-19 BioB Outpatient Clinic Study group %J Brain, b., immunity, 2021. Persistent psychopathology and neurocognitive impairment in COVID-19 survivors: effect of inflammatory biomarkers at three-month follow-up

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University of Copenhagen, Faculty of Health and Medical Sciences