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This systematic review and meta-analysis examines data from studies of patients with first-episode psychosis to estimate the prevalence of clinically relevant neuroradiological abnormalities detected using magnetic resonance imaging. Key Points: Question: How common are neuroradiological abnormalities in first-episode psychosis? Findings: In this systematic review and meta-analysis, we found approximately 6% of patients with first-episode psychosis had an abnormality that required a change in clinical management. The number of patients needed to scan to detect 1 clinically relevant abnormality was estimated to be 18. Meaning: These findings support the routine use of magnetic resonance imaging as part of the initial assessment in patients presenting with first-episode psychosis. Importance: Individuals presenting with first-episode psychosis (FEP) may have a secondary ("organic") etiology to their symptoms that can be identified using neuroimaging. Because failure to detect such cases at an early stage can have serious clinical consequences, it has been suggested that brain magnetic resonance imaging (MRI) should be mandatory for all patients presenting with FEP. However, this remains a controversial issue, partly because the prevalence of clinically relevant MRI abnormalities in this group is unclear. Objective: To derive a meta-analytic estimate of the prevalence of clinically relevant neuroradiological abnormalities in FEP. Data Sources: Electronic databases Ovid, MEDLINE, PubMed, Embase, PsychINFO, and Global Health were searched up to July 2021. References and citations of included articles and review articles were also searched. Study Selection: Magnetic resonance imaging studies of patients with FEP were included if they reported the frequency of intracranial radiological abnormalities. Data Extraction and Synthesis: Independent extraction was undertaken by 3 researchers and a random-effects meta-analysis of pooled proportions was calculated. Moderators were tested using subgroup and meta-regression analyses. Heterogeneity was evaluated using the I2 index. The robustness of results was evaluated using sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests. Main Outcomes and Measures: Proportion of patients with a clinically relevant radiological abnormality (defined as a change in clinical management or diagnosis); number of patients needed to scan to detect 1 such abnormality (number needed to assess [NNA]). Results: Twelve independent studies (13 samples) comprising 1613 patients with FEP were included. Of these patients, 26.4% (95% CI, 16.3%-37.9%; NNA of 4) had an intracranial radiological abnormality, and 5.9% (95% CI, 3.2%-9.0%) had a clinically relevant abnormality, yielding an NNA of 18. There were high degrees of heterogeneity among the studies for these outcomes, 95% to 73%, respectively. The most common type of clinically relevant finding was white matter abnormalities, with a prevalence of 0.9% (95% CI, 0%-2.8%), followed by cysts, with a prevalence of 0.5% (95% CI, 0%-1.4%). Conclusions and Relevance: This systematic review and meta-analysis found that 5.9% of patients presenting with a first episode of psychosis had a clinically relevant finding on MRI. Because the consequences of not detecting these abnormalities can be serious, these findings support the use of MRI as part of the initial clinical assessment of all patients with FEP. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms are common and important to people with Parkinson's disease (PD), but their etiology is poorly understood. Plasma neurofilament light (NfL) and p-tau181 are biomarkers of neuro-axonal degeneration and tau pathology respectively, which have yet to be explored in association with the affective and psychotic symptoms in PD. Objective: To investigate the relationship between plasma NfL and p-tau181 with the affective and psychotic symptoms in PD. Methods: We assessed the baseline concentration of plasma NfL and p-tau181 in a cohort of 108 patients with PD and 38 healthy controls. A subgroup of patients (n = 63) were assessed annually with clinical measures for up to 7 years. Psychotic symptoms were assessed using the Non-Motor Symptom Scale and affective symptoms were measured in the Hospital Anxiety and Depression Scale. Results: Baseline plasma NfL was a significant predictor of psychotic symptoms longitudinally across the study adjusted for age, Hoehn and Yahr stage, duration of follow up, duration of disease, baseline levodopa and dopamine agonist medication, and baseline cognition: (OR 8.15 [95% CI 1.40–47.4], p = 0.020). There was no association between NfL concentration and the cumulative prevalence of affective symptoms. Plasma p-tau181 concentration was not associated with psychotic or affective symptoms. Conclusion: These findings suggest psychotic symptoms are associated with greater neurodegeneration in PD. Further studies are needed to explore NfL as a potential biomarker for psychosis in PD. [ABSTRACT FROM AUTHOR]

Background: Autoimmune encephalitis (AE) is an important consideration during the diagnostic work-up of secondary mental disorders. Indeed, isolated psychiatric syndromes have been described in case reports of patients with underlying AE. Therefore, the authors performed a systematic literature review of published cases with AE that have predominant psychiatric/neurocognitive manifestations. The aim of this paper is to present the clinical characteristics of these patients. Methods: The authors conducted a systematic Medline search via Ovid, looking for case reports/series of AEs with antineuronal autoantibodies (Abs) against cell surface/intracellular antigens combined with predominant psychiatric/neurocognitive syndromes. The same was done for patients with Hashimoto encephalopathy/SREAT. Only patients with signs of immunological brain involvement or tumors in their diagnostic investigations or improvement under immunomodulatory drugs were included. Results: We identified 145 patients with AE mimicking predominant psychiatric/neurocognitive syndromes. Of these cases, 64% were female, and the mean age among all patients was 43.9 (±22.1) years. Most of the patients had Abs against neuronal cell surface antigens (55%), most frequently against the NMDA-receptor (N = 46). Amnestic/dementia-like (39%) and schizophreniform (34%) syndromes were the most frequently reported. Cerebrospinal fluid changes were found in 78%, electroencephalography abnormalities in 61%, and magnetic resonance imaging pathologies in 51% of the patients. Immunomodulatory treatment was performed in 87% of the cases, and 94% of the patients responded to treatment. Conclusions: Our findings indicate that AEs can mimic predominant psychiatric and neurocognitive disorders, such as schizophreniform psychoses or neurodegenerative dementia, and that affected patients can be treated successfully with immunomodulatory drugs. [ABSTRACT FROM AUTHOR]

When psychosis develops in NMDA receptor (NMDAR) antibody encephalitis, it usually has an acute or subacute onset, and antipsychotic treatment may be ineffective and associated with adverse effects. Serum NMDAR antibodies have been reported in a minority of patients with first-episode psychosis (FEP), but their role in psychosis onset and response to antipsychotic treatment is unclear. Sera from 387 patients with FEP (duration of psychosis <2 years, minimally or never treated with antipsychotics) undergoing initial treatment with amisulpride as part of the OPTiMiSE (Optimization of Treatment and Management of Schizophrenia in Europe) trial (ClinicalTrials.gov number NCT01248195) were tested for NMDAR IgG antibodies using a live cell–based assay. Symptom severity was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale at baseline and again after 4 weeks of treatment with amisulpride. At baseline, 15 patients were seropositive for NMDAR antibodies and 372 were seronegative. The seropositive patients had similar symptom profiles and demographic features to seronegative patients but a shorter duration of psychosis (median 1.5 vs. 4.0 months; p =.031). Eleven seropositive and 284 seronegative patients completed 4 weeks of amisulpride treatment: after treatment, there was no between-groups difference in improvement in Positive and Negative Syndrome Scale scores or in the frequency of adverse medication effects. These data suggest that in FEP, NMDAR antibody seropositivity alone is not an indication for using immunotherapy instead of antipsychotic medications. Further studies are required to establish what proportion of patients with FEP who are NMDAR antibody seropositive have coexisting cerebrospinal fluid inflammatory changes or other paraclinical evidence suggestive of a likely benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Recent findings implicate the complement C4 gene in gray matter loss in schizophrenia. In a large cohort of patients with first-episode psychosis (FEP), we aimed to (1) characterize the frequency of C4 gene copy number variations (CNVs) and HERV-K Ins/Del events as compared to that in healthy controls (HCs) and (2) evaluate whether C4 gene structural variants influence baseline clinical symptoms and treatment response to amisulpride. A total of 271 FEP subjects and 221 HCs were genotyped for C4 CNV and HERV-Ins/Del (C4A and C4B isoforms; C4-HERV structural forms [C4AL, C4AS, C4BL, C4BS] variations using droplet digital PCR. Overall, the gene frequencies of both C4 isoforms and C4-HERV structural forms did not significantly differ between groups. At the genotype level, we found that the C4 AL-AL-BL-BL genotype (AL-BL haplotype) was significantly more frequent in FEP as compared to HC. Apart from a marginal observation concerning the C4 AL-AL-BL-BL genotype (AL-BL haplotype), possibly reflecting a relationship with schizophrenia, we did not find any correlation between C4 genetic and clinical characteristics or treatment response in FEP. [ABSTRACT FROM AUTHOR]

The relationship between visual loss and psychosis is complex: congenital visual loss appears to be protective against the development of a psychotic disorder, particularly schizophrenia. In later life, however, visual deprivation or visual loss can give rise to hallucinosis, disorders of visual insight such as blindsight or Anton syndrome, or, in the context of neurodegenerative disorders, more complex psychotic presentations. We draw on a computational psychiatric approach to consider the foundational role of vision in the construction of representations of the world and the effects of visual loss at different developmental stages. Using a Bayesian prediction error minimization model, we describe how congenital visual loss may be protective against the development of the kind of computational deficits postulated to underlie schizophrenia, by increasing the precision (and consequent stability) of higher-level (including supramodal) priors, focusing on visual loss-induced changes in NMDA receptor structure and function as a possible mechanistic substrate. In simple terms, we argue that when people cannot see from birth, they rely more heavily on the context they extract from the other senses, and the resulting model of the world is more impervious to the false inferences, made in the face of inevitably noisy perceptual input, that characterize schizophrenia. We show how a Bayesian prediction error minimization framework can also explain the relationship between later visual loss and other psychotic symptoms, as well as the effects of visual deprivation and hallucinogenic drugs, and outline experimentally testable hypotheses generated by this approach. [ABSTRACT FROM AUTHOR]

Associations between influenza infection and psychosis have been reported since the eighteenth century, with acute "psychoses of influenza" documented during multiple pandemics. In the late 20th century, reports of a season-of-birth effect in schizophrenia were supported by large-scale ecological and sero-epidemiological studies suggesting that maternal influenza infection increases the risk of psychosis in offspring. We examine the evidence for the association between influenza infection and schizophrenia risk, before reviewing possible mechanisms via which this risk may be conferred. Maternal immune activation models implicate placental dysfunction, disruption of cytokine networks, and subsequent microglial activation as potentially important pathogenic processes. More recent neuroimmunological advances focusing on neuronal autoimmunity following infection provide the basis for a model of infection-induced psychosis, potentially implicating autoimmunity to schizophrenia-relevant protein targets including the N-methyl-D-aspartate receptor. Finally, we outline areas for future research and relevant experimental approaches and consider whether the current evidence provides a basis for the rational development of strategies to prevent schizophrenia. [ABSTRACT FROM AUTHOR]

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the antibody repertoire. Here we review the evidence for antibodies (to self-antigens as well as infectious organism and dietary antigens) as biomarkers of diagnosis, prognosis, and treatment response in psychotic disorders. Neuronal autoantibodies have current, and increasing, clinical utility in the diagnosis of organic or atypical psychosis syndromes. Antibodies to selected infectious agents show some promise in predicting cognitive impairment and possibly other symptom domains (eg, suicidality) within psychotic disorders. Finally, infectious antibodies and neuronal and other autoantibodies have recently emerged as potential biomarkers of response to anti-infective therapies, immunotherapies, or other novel therapeutic strategies in psychotic disorders, and have a clear role in stratifying patients for future clinical trials. As in nonpsychiatric disorders, combining biomarkers and large-scale use of "bottom-up" approaches to biomarker identification are likely to maximize the eventual clinical utility of antibody biomarkers in psychotic disorders. [ABSTRACT FROM AUTHOR]

Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19+ and reduced CD3+ lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post-mortem studies have found CD3+ and CD20+ lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody-mediated ( NSAb) central nervous system disease provides an antigen-specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo-controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis. [ABSTRACT FROM AUTHOR]

Background Exposure to infectious microorganisms has been implicated as an important risk factor in the development of psychotic disorders. Epidemiological and laboratory evidence suggests that exposure at various developmental periods may increase psychosis risk, from in utero through to childhood and adult life. Individuals who meet clinical high risk (CHR) criteria are at substantially increased risk of developing a psychotic disorder; however, no study to date has explored whether exposure to schizophrenia-associated pathogens is associated with clinical outcomes in this population. Methods Plasma samples from 254 subjects at ultra-high risk of psychosis from the EU-GEI cohort and 116 age- and sex-matched controls were tested for antibodies to the following infectious organisms: Toxoplasma gondii, herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus (EBV) and influenza. Samples were also tested for antibodies to the NMDA receptor using a fixed cell-based assay and for levels of S100B (a putative marker of blood-brain barrier disruption) and complement pathway protein expression. Only pathogens which predicted case-control status were taken through to further analysis looking at symptomatic associations and clinical outcome measures, which included the Positive and Negative Symptom Scale (PANSS), the Scale for Assessment of Negative Symptoms (SANS) and Global Assessment of Function (GAF). Results In logistic regression analysis, exposure to Toxoplasma was associated with increased risk of meeting CHR criteria (OR 2.66; p = 0.04), whereas EBV exposure was associated with decreased risk of meeting CHR criteria (OR 0.34; p = 0.006). Toxoplasma IgG antibody status was associated with higher SANS scores (p = 0.032) and higher GAF symptoms (p = 0.003) and disability scores (p = 0.003). EBV antibody status was associated with lower GAF scores (p = 0.007), indicating better functioning. In clinical outcome analysis, EBV antibody positivity was associated with a reduced risk of transition to psychosis (OR 0.44; p = 0.04), whereas Toxoplasma IgG seropositivity was associated with poorer functional outcomes at follow-up. The presence of NMDAR autoantibodies was associated with higher Toxoplasma IgM (p = 0.024), but not IgG (p = 0.972), titres. Furthermore, Toxoplasma IgM was associated with increased levels of serum S100B (p = 0.007) and with increased expression of Complement C4 (p = 0.018, FDR corrected), both of which have been independently implicated in psychosis risk. Discussion Toxoplasma exposure is associated with severity of negative symptoms and poor functional outcomes in CHR individuals, consistent with the known associations of Toxoplasma exposure in psychotic patients. Specific mechanisms by which Toxoplasma exposure might confer risk of poor outcomes include activation of specific complement pathway proteins, disruption of the blood-brain barrier and infection-induced production of brain-reactive autoantibodies. EBV exposure appears to have a mitigating effect, symptomatically and in terms of outcome, in this population, and as such may represent one of the first reported neurobiological protective factors for the CHR state and for the subsequent development of psychosis. [ABSTRACT FROM AUTHOR]

Highlights from the article: Su116peptide sharing between schizophrenia-related proteins and the influenza a virus may offer a link between immunity and psychotic disorders B Background: b Immunity and influenza infection are implicated in schizophrenia by historical epidemiological evidence and recent genome-wide association study (GWAS) findings. B Discussion: b This evidence suggests that peptide sharing occurs between schizophrenia-related proteins and specific proteins integral to the influenza virus rather across the entire virus proteome.

Blood-brain barrier pathology is recognized as a central factor in the development of many neurological disorders, but much less is known about the role of the blood-brain barrier in psychiatric disorders. Similarly, blood-gut barrier dysfunction is increasingly recognized as an important contributing factor in medicine far beyond narrowly-defined gastroenterological disorder, with neuropsychiatric disorders such as schizophrenia the focus of recent attention. Furthermore, in schizophrenia research there has been heightened interest in the aetiological role of systemic inflammation/immune responses and diet. As the blood-brain and blood-gut barriers are the chief interfaces via which systemic factors can influence the brain, they are a natural focus of interest to understand the neurobiology of psychotic disorders, potentially also representing a novel constellation of therapeutic targets. Measurement of blood-brain and blood-gut barrier function in humans is far from straightforward, a state of affairs which has perhaps led to barrier function research in psychosis being sidelined in the past. However new methodologies and models have enabled a new wave of research, bolstered by fundamental advances in our understanding of concepts such as neuroimmune privilege, the gut-brain axis, the role of the microbiome and brain autoimmunity. In this symposium, we will take a multidisciplinary tour of recent exciting developments focusing on multiple aspects of barrier dysfunction in the pathogenesis of psychotic disorders. Experts from the field of clinical psychiatry, neuroimmunology, genetics and epidemiology will be invited to share their findings and thoughts on the future of barrier function research in psychosis. We will explore the following questions: - Is there evidence for blood-brain and blood-gut barrier dysfunction in psychotic disorders? - Does barrier function cause psychotic disorder or is it a consequence of another pathology? - Is there a role for measurement of barrier function in the clinical management of patients with psychosis? - How does blood-gut barrier dysfunction impact the blood-brain barrier? - What is the significance of barrier function in light of recent immunological and inflammatory hypotheses of psychotic disorders, including neuronal autoantibody-associated psychosis? - Do schizophrenia-relevant genetic polymorphisms affect barrier function? - Could diet affect barrier function in a way that is relevant to the development of psychotic disorders? - How does the microbiome or systemic infection affect barrier function in psychotic disorders? - Could restitution of impaired barrier function represent a fruitful therapeutic strategy for the treatment of psychotic disorders? Dr. Bob Yolken will be the discussant, drawing on an extensive experience of schizophrenia research at the intersection of microbiology, immunology, genetics and epidemiology. [ABSTRACT FROM AUTHOR]

Abstract Background A relationship between non-neurological autoimmune (NNAI) disorders and psychosis has been widely reported but not yet subjected to meta-analysis. We conducted the first meta-analysis examining the association between NNAI disorders and psychosis and investigated the effect of 1) temporality (as determined by study design), 2) psychiatric diagnosis, and 3) specific autoimmune disorders. Methods Major databases were searched for articles published until April 2018; 31 studies, comprising data for >25 million individuals, were eligible. Using random-effects models, we examined the overall association between all NNAI disorders and psychosis; rheumatoid arthritis was examined separately given the well-established negative association with psychosis. Stratified analyses investigated the effect of temporality, psychiatric diagnosis, and specific NNAI disorders. Results We observed a positive overall association between NNAI disorders and psychosis (odds ratio [OR] = 1.26; 95% confidence interval [CI], 1.12–1.41) that was consistent across study designs and psychiatric diagnoses; however, considerable heterogeneity was detected (I 2 = 88.08). Patterns varied across individual NNAI disorders; associations were positive for pernicious anemia (OR = 1.91; 95% CI, 1.29–2.84), pemphigoid (OR = 1.90; 95% CI, 1.62–2.24), psoriasis (OR = 1.70; 95% CI, 1.51–1.91), celiac disease (OR = 1.53; 95% CI, 1.12–2.10), and Graves' disease (OR = 1.33; 95% CI, 1.03–1.72) and negative for ankylosing spondylitis (OR = 0.72; 95% CI, 0.54–0.98) and rheumatoid arthritis (OR = 0.65; 95% CI, 0.50–0.84). Conclusions While we observed a positive overall association between NNAI disorders and psychosis, this was not consistent across all NNAI disorders. Specific factors, including distinct inflammatory pathways, genetic influences, autoantibodies targeting brain proteins, and exposure to corticosteroid treatment, may therefore underlie this association. [ABSTRACT FROM AUTHOR]

Circulating autoantibodies against glutamatergic N -methyl-D-aspartate receptor (NMDAR) have been reported in a proportion of patients with psychotic disorders, raising hopes for more appropriate treatment for these antibody-positive patients. However, the prevalence of circulating autoantibodies against glutamatergic NMDAR in psychotic disorders remains controversial, with detection prevalence rates and immunoglobulin classes varying considerably between studies, perhaps because of different detection methods. Here, we compared the results of serum assays for a large cohort of patients with first-episode psychosis using classical cell-based assays in three labs and a single molecule-based imaging method. Most assays and single molecule imaging in live hippocampal neurons revealed the presence of circulating autoantibodies against glutamatergic NMDAR in approximately 5% of patients with first-episode psychosis. However, some heterogeneity between cell-based assays was clearly observed, highlighting the urgent need for new sensitive methods to detect the presence of low-titer autoantibodies against glutamatergic NMDAR in seropositive patients who cannot be clinically identified from seronegative ones. [ABSTRACT FROM AUTHOR]

• CHR subjects who transitioned to psychosis have higher baseline levels of VEGF. • CHR subjects who transitioned to psychosis have higher baseline IL-10/IL-6 ratio. • IL-6 and IL-4 levels were the main immune markers distinguishing CHR from controls. Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood–brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group. Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes. At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69–0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p <. 01). Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis. [ABSTRACT FROM AUTHOR]

• Viruses and immune function have been associated with psychosis through genetic and epidemiological research. • We critically evaluate the case for psychosis in COVID-19 through analysis of reported cases and historical precedents. • Potential infectious, post-infectious and neurodevelopmental aetiologies are explored. • Further appraisal of potential neurobiological and psychosocial mechanisms of 'COVID-19 psychosis' is urgently needed. Historical epidemiological perspectives from past pandemics and recent neurobiological evidence link infections and psychoses, leading to concerns that COVID-19 will present a significant risk for the development of psychosis. But are these concerns justified, or mere sensationalism? In this article we review the historical associations between viral infection and the immune system more broadly in the development of psychosis, before critically evaluating the current evidence pertaining to SARS-CoV-2 and risk of psychosis as an acute or post-infectious manifestation of COVID-19. We review the 42 cases of psychosis reported in infected patients to date, and discuss the potential implications of in utero infection on subsequent neurodevelopment and psychiatric risk. Finally, in the context of the wider neurological and psychiatric manifestations of COVID-19 and our current understanding of the aetiology of psychotic disorders, we evaluate possible neurobiological and psychosocial mechanisms as well as the numerous challenges in ascribing a causal pathogenic role to the infection. [ABSTRACT FROM AUTHOR]