key: cord-0990462-bt7zkarw
authors: Ng, Qin Xiang; Yeo, Wee Song; Lim, Donovan Yutong; Chee, Kuan Tsee
title: Re-examining the association between COVID-19 and psychosis
date: 2020-06-23
journal: Psychosomatics
DOI: 10.1016/j.psym.2020.06.013
sha: 9ae28cb90a9024b7ab5ec9ce47d0cef8ef4e4a39
doc_id: 990462
cord_uid: bt7zkarw

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Qin Xiang Ng conceived the original idea for the manuscript while Kuan Tsee Chee supervised the study. All authors contributed to the writing and proofreading of the final manuscript. The final manuscript was discussed and approved by all authors. All authors are responsible for the content and writing of the paper.

We read with great interest the recent report by Ferrando et al., which described three patients who presented to the Emergency Department with similar presentations of agitation, disorganization, paranoid ideation and auditory hallucinations. 1 They were all tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) albeit the method of testing was not specified, and found to be positive for the Coronavirus Disease 2019 (COVID-19).

We have some thoughts on the observed association and hope this would generate greater discourse on the subject.

First, possible infective origins of mental illness were probably first hypothesized in 1845 by French neurologist Jean Esquirol, and the theory later refined by Swiss psychiatrist Eugen Bleuler in the 19th century. 2 Given the systemic effects of SARS-CoV-2, which are wellreviewed in literature, it is certainly plausible that the coronavirus could, directly or indirectly, affect the brain and the central nervous system. However, in this case, we are mindful that the observed association in this report could also be fortuitous as this is a small sample of three individual cases, and in terms of epidemiological evidence, the onset of first-episode psychosis (FEP) in the 30s is not uncommon. In a study of 555 individuals with FEP, the median age of onset was found to be 27.3 years (interquartile range 21.2, 36.5). 3 Second, the authors appropriately mentioned the possibility of a stress-related trigger from the COVID-19 pandemic in psychiatrically vulnerable individuals. We recognise that all three of the patients presented had a prior psychiatric diagnosis: patient 1 and patient 2 both had a prior diagnosis of panic disorder while patient 3 had opioid use disorder, on methadone maintenance. Anxiety is the mother of psychopathology in predisposing, precipitating, and perpetuating symptoms. All three patients also appeared to respond to clonazepam, lorazepam and low doses of quetiapine, which all exert anxiolytic effects.

In terms of their physical symptoms (or the lack thereof) and stable hemodynamics, there was no evidence of an excessive immunologic response. Interestingly, Esquirol himself was also of the view that some mental illnesses may be caused by emotional disturbances rather than by organic brain damage. 2 If we accept the prevailing biopsychosocial model of mental illness, psychosis is likely to have multiple causes, including genetic, neurobiological, psychological and environmental factors. Psychiatric manifestations may be the indirect ("reactive" stress) result of this pandemic rather than the direct pathophysiological effects of the virus.

Third, the classification of acute-onset psychotic disorders is rather inexact, and although the authors reported that the patients did not verbalise preoccupation with COVID-19, this may be difficult to elicit from the patients when they are in an acute agitated and psychotic state.

Fourth, clinically, the elevations in C-reactive protein (0.6 to 1.9 mg/dL) were relatively minor and could well be within normal variations. 'Normal' C-reactive protein (CRP) levels have not been rigorously studied or defined and the levels are known to vary with population, age and ethnicity. 4, 5 To play devil's advocate, we know that struggling against restraints, physical agitation or other common events could all result in an elevated CRP. Due to the highly variable causality, a single CRP value at admission lacks clinical utility and is difficult to interpret in isolation.

Last but not least, it would be of value to follow up these patients and their symptoms longitudinally. Outcomes of patients with FEP are known to be heterogeneous, ranging from complete recovery to recurrent and resistant psychotic symptoms. This may give us new insights beyond that of a 'snapshot' picture or cross-sectional mental state examination. The SARS-CoV-2 is undoubtedly a novel virus and there is much to be learnt from it -and it does surprise us sometimes.

COVID-19 Psychosis: A potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response? Psychosomatics

Viruses, schizophrenia, and bipolar disorder. Clinical microbiology reviews

Environmental factors and the age at onset in first episode psychosis

Gender and C-reactive protein: data from the Multiethnic Study of

Interpretation of circulating C-reactive protein levels in adults: body mass index and gender are a must

The authors report no conflicts of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors alone are responsible for the content and writing of the article.

No conflict of interests to declare.