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Introduction Widespread white matter abnormalities and alterations in glutamate levels have been reported in patients with schizophrenia. We hypothesized that alterations in white matter integrity and glutamate levels in individuals at clinical high risk (CHR) for psychosis are associated with the subsequent development of psychosis. Methods Participants included 33 antipsychotic naive CHR (Female 7/Male 26, Age 19.55 (4.14) years) and 38 healthy controls (Female 10/Male 28, Age 20.92 (3.37) years). Whole brain diffusion tensor imaging for fractional anisotropy (FA) and right frontal white matter proton magnetic resonance spectroscopy for glutamate levels were acquired. CHR participants were clinically followed for 2 years to determine conversion to psychosis. Results CHR participants that transitioned to psychosis (N = 7, 21%) were characterized by significantly lower FA values in the posterior thalamic radiation compared to those who did not transition and healthy controls. In the CHR group that transitioned to psychosis only, positive exploratory correlations between glutamate levels and FA values of the posterior thalamic radiation and the retrolenticular part of the internal capsule and a negative correlation between glutamate levels and the cingulum FA values were found. Conclusion The results of the present study highlight that alterations in white matter structure and glutamate are related with the conversion to psychosis.

Background Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g., psychosis in bipolar disorder vs. schizophrenia). Computational modeling makes it possible to identify and mathematically differentiate behaviorally unobservable, specific reinforcement learning differences in patients with schizophrenia versus other disorders, likely owing to a higher reliance on prediction error–driven learning associated with basal ganglia and underreliance on explicit value representations associated with orbitofrontal cortex. Methods We used a well-established probabilistic reinforcement learning task to replicate those findings in individuals with schizophrenia both on (n = 120) and off (n = 44) antipsychotic medications and included a patient comparison group of bipolar patients with psychosis (n = 60) and healthy control subjects (n = 72). Results Using accuracy, there was a main effect of group (F3,279 = 7.87, p Conclusions Both medicated and unmedicated patients showed overreliance on prediction error–driven learning as well as significantly higher noise and value-related memory decay, compared with the healthy control subjects and the patients with bipolar disorder. Additionally, the computational model parameters capturing these processes can significantly improve patient/control classification, potentially providing useful diagnosis insight.

Choline, folic acid, and Vitamin D are essential for fetal brain development that may be the first steps in the pathogenesis of the psychotic spectrum. Micronutrient deficiencies have been associated with changes in fetal brain development, manifest as early problems in childhood behavior, and cognition, and later as increased incidence of psychotic and autism spectrum disorders. Micronutrient supplements may not only prevent deficiency, but they may also positively affect brain development in the context of other maternal risk factors, including maternal infection, stress, inflammation, and substance abuse. Many genes associated with later psychotic illness are highly expressed in the fetal brain, where they are responsible for various neurodevelopmental mechanisms. Interaction of micronutrient vitamins with these genetically programmed mechanisms to prevent pathological brain development associated with later psychosis is under active investigation. In addition to their effects on brain development, micronutrient vitamins have effects on other aspects of gestation and fetal development, including the prevention of premature delivery and other developmental abnormalities. Supplemental micronutrient vitamins should be part of good prenatal care, as has already happened for folic acid and Vitamin D and is now advocated by the American Medical Association for choline. The benefits of these micronutrient supplements include protection of brain development and the possibility of decreased risk for future psychotic disorders in those children who are either genetically or environmentally vulnerable. The purpose of this review is to present the current evidence supporting the safety and effectiveness of micronutrients in gestation and to suggest areas for future research.

Epidemiologic studies have provided evidence that prenatal exposure to maternal infection is associated with an increased risk of developing schizophrenia in the offspring. Research over the past decade has added further to our understanding of the role of prenatal infection in schizophrenia risk. These investigations include several well-powered designs, and like some earlier studies, measured maternal antibodies to specific infectious agents in stored serum samples and large registers to identify clinically diagnosed infections during pregnancy. Convergent findings from antibody studies suggest that prenatal maternal infection with Toxoplasma gondii is associated with increased schizophrenia risk in the offspring, while associations with HSV-2 infection are likely attributable to confounding. Maternal influenza infection remains a viable candidate for schizophrenia, based on an early serological study, though there has been only one attempt to replicate this finding, with a differing methodology. A prior association between maternal serologically confirmed cytomegalovirus infections require further study. Clinically diagnosed maternal infection, particularly bacterial infection, also appears to be associated with increased risk of offspring schizophrenia, and heterogeneity in these findings is likely due to methodological differences between studies. Further clarification may be provided by future studies that address the timing, type, and clinical features of infections. Important insight may be gained by examining the long-term offspring outcomes in emerging epidemics such as Zika virus and COVID-19, and by investigating the interaction between exposure to prenatal infection and other risk or protective factors.

Background Psychiatric disorders are categorized using self-report and observational information rather than biological data. There is also considerable symptomatic overlap between different types of psychiatric disorders, which makes diagnostic categorization and multi-class classification challenging. Methods In this work, we propose a unified framework for supervised classification and unsupervised clustering of psychotic disorders using brain imaging data. A new multi-scale recurrent neural network (MsRNN) model was developed and applied to fMRI time courses (TCs) for multi-class classification. The high-level representations of the original TCs were then submitted to a tSNE clustering model for visualizing the group differences between disorders. A leave-one-feature-out approach was used for disorder-related biomarker identification. Results When studying fMRI from schizophrenia, psychotic bipolar disorder, schizoaffective disorder, and healthy individuals, the accuracy of a 4-class classification reached 46%, significantly above chance. The hippocampus, supplementary motor area and paracentral lobule were discovered as the most contributing regional TCs in the multi-class classification. Beyond this, visualization of the tSNE clustering suggested that the disease severity can be captured and schizoaffective disorder (SAD) may be separated into two subtypes. SAD cluster1 has significantly higher Positive And Negative Syndrome Scale (PANSS) scores than SAD cluster2 in PANSS negative2 (emotional withdrawal), general2 (anxiety), general3 (guilt feelings), general4 (tension). Conclusions The proposed deep classification and clustering framework is not only able to identify psychiatric disorders with high accuracy, but also interpret the correlation between brain networks and specific psychiatric disorders, and reveal the relationship between them. This work provides a promising way to investigate a spectrum of similar disorders using neuroimaging-based measures.

Delusions are rigid beliefs held with high certainty despite contradictory evidence. Notwithstanding decades of research, we still have a limited understanding of the computational and neurobiological alterations giving rise to delusions. In this review, we highlight a selection of recent work in computational psychiatry aimed at developing quantitative models of inference and its alterations, with the goal of providing an explanatory account for the form of delusional beliefs in psychosis. First, we assess and evaluate the experimental paradigms most often used to study inferential alterations in delusions. Based on our review of the literature and theoretical considerations, we contend that classic draws-to-decision paradigms are not well-suited to isolate inferential processes, further arguing that the commonly cited ‘jumping-to-conclusion’ bias may reflect neither delusion-specific nor inferential alterations. Second, we discuss several enhancements to standard paradigms that show promise in more effectively isolating inferential processes and delusion-related alterations therein. We further draw on our recent work to build an argument for a specific failure mode for delusions consisting of prior overweighting in high-level causal inferences about partially observable hidden states. Finally, we assess plausible neurobiological implementations for this candidate failure mode of delusional beliefs and outline promising future directions in this area.

Despite previous neuroimaging studies demonstrating morphological abnormalities of the thalamus and other subcortical structures in patients with schizophrenia, the potential role of the thalamus and its subdivisions in the pathophysiology of this illness remains elusive. It is also unclear whether similar changes of these structures occur in individuals at high risk for psychosis. In this study, magnetic resonance imaging was employed with the Multiple Automatically Generated Templates (MAGeT) brain segmentation algorithm to determine volumes of the thalamic subdivisions, the striatum (caudate, putamen, and nucleus accumbens), and the globus pallidus in 62 patients with schizophrenia, 38 individuals with an at-risk mental state (ARMS) [4 of whom (10.5%) subsequently developed schizophrenia], and 61 healthy subjects. Cognitive function of the patients was assessed by using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Thalamic volume (particularly the medial dorsal and ventral lateral nuclei) was smaller in the schizophrenia group than the ARMS and control groups, while there were no differences for the striatum and globus pallidus. In the schizophrenia group, the reduction of thalamic ventral lateral nucleus volume was significantly associated with lower BACS score. The pallidal volume was positively correlated with the dose of antipsychotic treatment in the schizophrenia group. These results suggest that patients with schizophrenia, but not those with ARMS, exhibit volume reduction in specific thalamic subdivisions, which may underlie core clinical features of this illness.

Introduction The neural correlates of the cognitive dysfunction in first-episode psychosis (FEP) are still unclear. The present review and meta-analysis provide an update of the location of the abnormalities in the fMRI-measured brain response to cognitive processes in individuals with FEP. Methods Systematic review and voxel-based meta-analysis of cross-sectional fMRI studies comparing neural responses to cognitive tasks between individuals with FEP and healthy controls (HC) according to PRISMA guidelines. Results Twenty-six studies were included, comprising 598 individuals with FEP and 567 HC. Individual studies reported statistically significant hypoactivation in the dorsolateral prefrontal cortex (6 studies), frontal lobe (8 studies), cingulate (6 studies) and insula (5 studies). The meta-analysis showed statistically significant hypoactivation in the left anterior insula, precuneus and bilateral striatum. Conclusions While the studies tend to highlight frontal hypoactivation during cognitive tasks in FEP, our meta-analytic results show that the left precuneus and insula primarily display aberrant activation in FEP that may be associated with salience attribution to external stimuli and related to deficits in perception and regulation.

Background: This study tested the hypotheses that (i) the relationship between a history of childhood abuse and severity of psychosis is mediated by loneliness; (ii) the relationship between loneliness and psychosis is mediated by within-person fluctuations in depressive and anxious feelings.Methods: Fifty-nine individuals with non-affective psychotic disorder rated the intensity of loneliness, positive symptoms, and depressive and anxious feelings during repeated moments in daily life (Experience Sampling Method). Childhood abuse was assessed retrospectively using the 'Childhood Experience of Care and Abuse' interview. To test the mediation hypotheses, a multilevel structural equation modeling paradigm was used.Results: As predicted, the relationship between severity of childhood abuse and positive symptoms was mediated by loneliness (b = 0.08, 95% CI [0.02, 0.13], p = 0.005). In turn, the relationship between loneliness and positive symptoms was mediated by within-person fluctuations in both depressive (b = 0.04, 95% CI [0.02, 0.06], p < 0.001) and anxious (b = 0.02, 95% CI [0.01, 0.03], p = 0.002) symptomatology. Depression was a stronger mediator than anxiety (b = 0.02, 95% CI [0.00, 0.04], p = 0.027).Conclusions: Our findings highlight the role of childhood abuse and loneliness in the severity of psychosis in daily life.(c) 2019 Elsevier B.V. All rights reserved.

Background A decline in cortical thickness during early life appears to be a normal neuromaturational process. Accelerated cortical thinning has been linked with conversion to psychosis among individuals at clinical high risk for psychosis (CHR-P). Previous research indicates that exposure to life event stress (LES) is associated with exaggerated cortical thinning in both healthy and clinical populations, and LES is also linked with conversion to psychosis in CHR-P. To date, there are no reports on the relationship of LES with cortical thickness in CHR-P. This study examines this relationship and whether LES is linked with cortical thinning to a greater degree in individuals at CHR-P who convert to psychosis compared with individuals at CHR-P who do not convert and healthy control subjects. Methods Controlling for age and gender (364 male, 262 female), this study examined associations between LES and baseline cortical thickness in 436 individuals at CHR-P (375 nonconverters and 61 converters) and 190 comparison subjects in the North American Prodrome Longitudinal Study. Results Findings indicate that prebaseline cumulative LES is associated with reduced baseline cortical thickness in several regions among the CHR-P and control groups. Evidence suggests that LES is a risk factor for thinner cortex to the same extent across diagnostic groups, while CHR-P status is linked with thinner cortex in select regions after accounting for LES. Conclusions This research provides additional evidence to support the role of LES in cortical thinning in both healthy youth and those at CHR-P. Potential underlying mechanisms of the findings and implications for future research are discussed.

Social isolation has been suggested to foster paranoia. Here we investigate whether social company (i.e., being alone vs. not) and its nature (i.e., stranger/distant vs. familiar other) affects paranoia differently depending on psychosis risk. Social interactions and paranoid thinking in daily life were investigated in 29 patients with clinically stable non-affective psychotic disorders, 20 first-degree relatives, and 26 controls (n = 75), using the experience sampling method (ESM). ESM was completed up to ten times daily for 1 week. Patients experienced marginally greater paranoia than relatives [b = 0.47, p = 0.08, 95% CI (− 0.06, 1.0)] and significantly greater paranoia than controls [b = 0.55, p = 0.03, 95% CI (0.5, 1.0)], but controls and relatives did not differ [b = 0.07, p = 0.78, 95% CI (− 0.47, 0.61)]. Patients were more often alone [68.5% vs. 44.8% and 56.2%, respectively, p = 0.057] and experienced greater paranoia when alone than when in company [b = 0.11, p = 0.016, 95% CI (0.02, 0.19)]. In relatives this was reversed [b = − 0.17, p b = − 0.02, p = 0.67, 95% CI (− 0.09, 0.06)]. The time-lagged association between being in social company and subsequent paranoia was non-significant and paranoia did not predict the likelihood of being in social company over time (both p’s = 0.68). All groups experienced greater paranoia in company of strangers/distant others than familiar others [X2(2) = 4.56, p = 0.03] and being with familiar others was associated with lower paranoia over time [X2(2) = 4.9, p = 0.03]. Patients are frequently alone. Importantly, social company appears to limit their paranoia, particularly when being with familiar people. The findings stress the importance of interventions that foster social engagement and ties with family and friends.

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

Introduction: A strong link between voice-hearing experience and childhood trauma has been established. The aim of this study was to identify whether there were unique clusters of childhood trauma subtypes in a sample across the clinical spectrum of auditory verbal hallucinations (AVH) and to examine clinical and phenomenological features across these clusters. Methods: Combining two independent international datasets (the Netherlands and Australia), childhood trauma subtypes were examined using hierarchical cluster analysis. Clinical and phenomenological characteristics were compared across emerging clusters using MANOVA and chi-squared analyses. Results: The total sample (n = 413) included 166 clinical individuals with a psychotic disorder and AVH, 122 non-clinical individuals with AVH and 125 non-clinical individuals without AVH. Three clusters emerged: (1) low trauma (n = 299); (2) emotion-focused trauma (n = 71); (3) multi-trauma (n = 43). The three clusters differed significantly on their AVH ratings of amount of negative content, with trend-level effects for loudness, degree of negative content and degree of experienced distress. Furthermore, perceptions of voices being malevolent, benevolent and resistance towards voices differed significantly. Conclusion: The data revealed different types of childhood trauma had different relationships between clinical and phenomenological features of voice-hearing experiences. Thus, implicating different mechanistic pathways and a need for tailored treatment approaches.

Psychotic and autistic symptoms are related to social functioning in individuals with psychotic disorders (PD). The present study used a network approach to (1) evaluate the interactions between autistic symptoms, psychotic symptoms, and social functioning, and (2) investigate whether relations are similar in individuals with and without PD. We estimated an undirected network model in a sample of 504 PD, 572 familial risk for psychosis (FR), and 337 typical comparisons (TC), with a mean age of 34.9 years. Symptoms were assessed with the Autism Spectrum Quotient (AQ; 5 nodes) and the Community Assessment of Psychic Experiences (CAPE; 9 nodes). Social functioning was measured with the Social Functioning Scale (SFS; 7 nodes). We identified statistically significant differences between the FR and PD samples in global strength (P < .001) and network structure (P < .001). Our results show autistic symptoms (social interaction nodes) are negatively and more closely related to social functioning (withdrawal, interpersonal behavior) than psychotic symptoms. More and stronger connections between nodes were observed for the PD network than for FR and TC networks, while the latter 2 were similar in density (P = .11) and network structure (P = .19). The most central items in strength for PD were bizarre experiences, social skills, and paranoia. In conclusion, specific autistic symptoms are negatively associated with social functioning across the psychosis spectrum, but in the PD network symptoms may reinforce each other more easily. These findings emphasize the need for increased clinical awareness of comorbid autistic symptoms in psychotic individuals.

AIM: We examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms. METHOD: This cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight

Introduction Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]). Conclusion A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.

Cannabis use is common in people with psychotic disorders. However, the effect of cannabis on cognition in psychosis remains unclear. Our study investigates relationships between the history of cannabis use and cognitive performance in patients with first-episode psychosis (FEP) during a one-year follow-up.The present study included FEP (In the FEP group, men used cannabis more frequently than women. In the crude regression model for FEP patients, never having used cannabis was associated with a better neurocognitive profile at 12 months. In the full model, more severe anxiety symptoms were associated with better neurocognition at two months, and less severe negative symptoms were associated with better neurocognition at 12 months. Cannabis use was not associated with social cognition. No associations between cognitive performance and cannabis use emerged in the controls.Negative and affective symptom severity in FEP was associated with cognitive performance to a greater degree than a lifetime history of cannabis use.

Personality analysis is an important area of research in several fields, including psychology, psychiatry, and neuroscience. With the recent dramatic improvements in machine learning, it has also become a popular research area in computer science. While the current computational methods are able to interpret behavioral cues (e.g., facial expressions, gesture, and voice) to estimate the level of (apparent) personality traits, accessible assessment tools are still substandard for practical use, not to mention the need for fast and accurate methods for such analyses. In this study, we present multimodal deep architectures to estimate the Big Five personality traits from (temporal) audio-visual cues and transcribed speech. Furthermore, for a detailed analysis of personality traits, we have collected a new audio-visual dataset, namely: Self-presentation and Induced Behavior Archive for Personality Analysis (SIAP). In contrast to the available datasets, SIAP introduces recordings of induced behavior in addition to self-presentation (speech) videos. With thorough experiments on SIAP and ChaLearn LAP First Impressions datasets, we systematically assess the reliability of different behavioral modalities and their combined use. Furthermore, we investigate the characteristics and discriminative power of induced behavior for personality analysis, showing that the induced behavior indeed includes signs of personality traits.

Background There is emerging evidence for abnormal beta oscillations in psychosis. Beta oscillations are likely to play a key role in the coordination of sensorimotor information that is crucial to healthy mental function. Growing evidence suggests that beta oscillations typically manifest as transient beta bursts that increase in probability following a motor response, observable as post-movement beta rebound. Evidence indicates that post-movement beta rebound is attenuated in psychosis, with greater attenuation associated with greater symptom severity and impairment. Delineating the functional role of beta bursts therefore may be key to understanding the mechanisms underlying persistent psychotic illness. Methods We used concurrent electroencephalography and functional magnetic resonance imaging to identify blood oxygen level–dependent correlates of beta bursts during the n-back working memory task and intervening rest periods in healthy participants (n = 30) and patients with psychosis (n = 48). Results During both task blocks and intervening rest periods, beta bursts phasically activated regions implicated in task-relevant content while suppressing currently tonically active regions. Patients showed attenuated post-movement beta rebound that was associated with persisting disorganization symptoms as well as impairments in cognition and role function. Patients also showed greater task-related reductions in overall beta burst rate and showed greater, more extensive, beta burst–related blood oxygen level–dependent activation. Conclusions Our evidence supports a model in which beta bursts reactivate latently maintained sensorimotor information and are dysregulated and inefficient in psychosis. We propose that abnormalities in the mechanisms by which beta bursts coordinate reactivation of contextually appropriate content can manifest as disorganization, working memory deficits, and inaccurate forward models and may underlie a core deficit associated with persisting symptoms and impairment.

Purpose This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids. Methods The protocol was published in Open Science Framework. We used the PECOS framework to frame the review question. Studies published between January 1, 2000, and January 4, 2021, from North America, Europe, the United Kingdom, Australia, and New Zealand were systematically identified and screened through searching electronic databases, citations, and by contacting experts. Risk of bias assessments were performed. Data were synthesized using the lumping technique. Results Overall, 6512 records were screened and 38 were selected for inclusion. 37 of the 38 studies included in this review show a connection between at least one aspect of mental disorder and opioid overdose. The largest body of evidence exists for internalizing disorders generally and mood disorders specifically, followed by anxiety disorders, although there is also moderate evidence to support the relationship between thought disorders (e.g., schizophrenia, bipolar disorder) and opioid overdose. Moderate evidence also was found for the association between any disorder and overdose. Conclusion Nearly all reviewed studies found a connection between mental disorder and overdose, and the evidence suggests that having mental disorder is associated with experiencing fatal and non-fatal opioid overdose, but causal direction remains unclear.

Objectives To estimate the diagnosed incidence of non-affective psychotic disorder between the ages of 13 and 19 years in South-Western British Columbia (BC) and to examine variation in risk by sex, family and neighbourhood income, family migration background, parent mental health contact and birth year. Methods Linked individual-level administrative data were used to construct a cohort of individuals born in 1990–1998 and residing in South-Western BC ( n = 193,400). Cases were identified by either one hospitalization or two outpatient physician visits within 2 years with a primary diagnosis of a non-affective psychotic disorder (ICD-10: F20–29, ICD-9: 295, 297, 298). We estimated cumulative incidence, annual cumulative incidence and incidence rate between the ages of 13 and 19 years, and conducted Cox proportional hazards regression to estimate associations between sociodemographic factors and risk over the study period. Results We found that 0.64% of females and 0.88% of males were diagnosed with a non-affective psychotic disorder between the ages of 13 and 19 years, with increasing risk observed over the age range, especially amongst males. Incidence rate over the entire study period was 106 per 100,000 person-years for females and 145 per 100,000 person-years for males. Risk of diagnosis was elevated amongst those in low-income families and neighbourhoods, those with a parent who had a health service contact for a mental disorder, and more recent birth cohorts. Risk was reduced amongst children of immigrants compared to children of non-migrants. Conclusions Findings from this study provide important information for health service planning in South-Western BC. Future work should examine whether variations in diagnosed incidence is driven by differences in health service engagement or reflect genuine differences in risk.

Aim\ud To compare social, recreational and independent functioning among persons with psychosis across two geo-cultural contexts, we adapted the well-established Social Functioning Scale (SFS) and translated it into French and Tamil. We present the development and psychometric testing of this adaptation, the SFS-Early Intervention.\ud \ud Methods\ud Sixteen items were added to reflect contemporary youth activities (e.g., online games) and 31 items adapted to enhance applicability and/or include context-specific examples (e.g., ‘church activity’ replaced with ‘religious/spiritual activity’). Psychometric properties and participant feedback were evaluated.\ud \ud Results\ud Test–retest reliability (ICCs) ranged from 0.813 to 0.964. Internal consistency (Cronbach's α) ranged from .749 to .936 across sites and languages. Correlations with original subscales were high. The scale was rated easy to complete and understand.\ud \ud Conclusions\ud The SFS-Early Intervention is a promising patient-reported measure of social, recreational and independent functioning. Our approach shows that conceptually sound existing measures are adaptable to different times and contexts.

Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56-7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73-10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk-for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.

Background Schizophrenia is associated with elevated levels of circulating C-reactive protein (CRP) and other inflammatory markers, but it is unclear whether these associations extend to psychotic symptoms occurring in adolescence in the general population. A symptom-based approach may provide important clues for apparent trans-diagnostic effect of inflammation, which is also associated with depression and other psychiatric disorders. Methods Based on data from 2421 participants from the Avon Longitudinal Study of Parents and Children birth cohort, we examined associations of serum CRP levels assessed around age 16 with ten positive and ten negative symptoms of psychosis assessed using questionnaires around age 17, using both individual symptoms and symptom dimension scores as outcomes. Regression models were adjusted for sex, body mass index, depressive symptoms, substance use, and other potential confounders. Results Most prevalent positive symptoms were paranoid ideation (4.8%), visual (4.3%) and auditory (3.5%) hallucinations. Negative symptoms were more strongly correlated with concurrent depressive symptoms (r=0.51; P, Highlights • We examined psychotic symptoms in adolescents from a population-based birth cohort. • Common positive symptoms were paranoid ideation, visual and auditory hallucinations. • Negative symptoms were correlated with depressive and positive symptoms. • CRP was similarly associated with positive and negative symptom dimension scores. • CRP was specifically associated with auditory hallucinations and anhedonia.

17β-estradiol treatment has shown benefit against schizophrenia symptoms, however longterm use may be associated with negative side-effects. Selective estrogen receptor modulators, such as raloxifene and tamoxifen, have been proposed as suitable alternatives to 17β- estradiol. An isomer of 17β-estradiol, 17α-estradiol, is considered less carcinogenic, and non-feminising in males, however little is known about its potential as a treatment for schizophrenia. Moreover, the mechanism underlying the therapeutic action of estrogens remains unclear. We aimed to investigate the ability of these estrogenic compounds to attenuate psychosis-like behaviour in rats. We used two acute pharmacologically-induced assays of psychosis-like behaviour: psychotomimetic drug-induced hyperlocomotion and disruption of prepulse inhibition (PPI). Female Long Evans rats were either intact, ovariectomised (OVX), or OVX and chronically treated with 17β-estradiol, 17α-estradiol, raloxifene or tamoxifen. Only 17β-estradiol treatment attenuated locomotor hyperactivity induced by the indirect dopamine receptor agonist, methamphetamine. 17β-estradiol- and tamoxifen-treated rats showed attenuated methamphetamine- and apomorphine (dopamine D1/D2 receptor agonist)- induced disruption of PPI. Raloxifene-treated rats showed attenuated apomorphineinduced PPI disruption only. Baseline PPI was significantly reduced following OVX, and this deficit was reversed by all estrogenic compounds. Further, PPI in OVX rats was increased following administration of apomorphine. This study confirms a protective effect of 17β- estradiol in two established animal models of psychosis, while tamoxifen showed beneficial effects against PPI disruption. In contrast, 17α-estradiol and raloxifene showed little effect on dopamine receptor-mediated psychosis-like behaviours. This study highlights the utility of some estrogenic compounds to attenuate psychosis-like behaviour in rats, supporting the notion that estrogens have therapeutic potential for psychotic disorders.

Background: Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among them, benzydamine (BZY), normally prescribed as an OTC anti-inflammatory drug, is reportedly being diverted and recreationally used. Objective: The aim of this study was to investigate how the misuse of BZY has been reported, illustrating its psychotropic molecular mechanism, and studying its psychopathological effects. Methods: We firstly conducted a systematic review of the literature concerning the abuse of BZY and its effects. For data gathering purposes, both PRISMA and PROSPERO guidelines were followed. All research methods were approved by PROSPERO (identification code CRD42020187266). Second, we analysed BZY-related data from the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs) database recorded during 2005-2020 regarding its abuse. Results: Eleven articles, published during 1997-2019, were included in our systematic review, including five case reports, four surveys, and two retrospective case series analyses. While nine articles dealt with the recreational use of BZY, two described an oral overdose of the drug. When specified, dosages of BZY consumed ranged from 500 to 1500mg. The EMA dataset contained three cases of BZY abuse. Conclusion: Results from the systematic review showed BZY might be diverted for typical hallucinogenic properties occurring at high dosages. Healthcare professionals should be warned about a possible misuse/abuse of a commonly prescribed anti-inflammatory drug and be vigilant when prescribing it. Physicians working in emergency units should know that psychotic symptoms may be related to BZY abuse.

A cross-sectional association between visual impairment and psychosis exists, but longitudinal evidence from children and young people is limited. We investigated whether childhood visual acuity was associated with subsequent psychotic experiences. Our sample was 6686 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We investigated whether our primary exposures, best corrected visual acuity at ages 7 and 11, were associated with psychotic experiences at ages 17 and 24. We also tested whether the following exposures at ages 7 and 11 were associated with subsequent psychotic experiences: requiring glasses, presence of any visual impairment, and between-eye visual acuity difference; and at age 7: strabismus, measures of binocular vision, history of eye patch, near vision impairment, and abnormal saccadic or pursuit eye movements. Analyses used multilevel models before and after adjusting for confounders. Odds of psychotic experiences increased with each 0.1-point deterioration in visual acuity score at age 11 (adjusted odds ratio [AOR] 1.23; 95% confidence interval [CI] 1.06–1.42), and at age 7 (AOR 1.18; 95% CI 1.00–1.40). Wearing glasses and visual impairment at age 11 were associated with psychotic experiences (AOR 1.63; 95% CI 1.21–2.19; AOR 1.64; 95% CI 1.23–2.19, respectively). There was no evidence of an association with other visual exposures. Visual acuity impairment in childhood is associated with psychotic experiences in late adolescence. Future research should aim to elucidate the nature of this association.

Background Previous research has reported increased risk for psychosis among individuals who use cannabis during adolescence. We conducted a systematic review and meta-analysis to investigate the interaction between adolescent cannabis use and other factors in moderating risk for psychosis later in life. Method We searched four electronic databases in June 2020 for articles that assessed adolescent cannabis use, had psychosis as an outcome and analyzed for the association between adolescent cannabis use and psychosis. Analysis was done using random-effects meta-analysis and narrative synthesis. Results A total of 63 studies were included in the narrative review and 18 studies were included in the meta-analysis. Adolescent cannabis use was found to increase risk for psychosis (RR = 1.71 (95%CI, 1.47–2.00, p Conclusion Adolescent cannabis use is associated with an increased risk for psychosis later in life. In addition, there are factors that moderate this relationship; therefore there is a need for research to assess the interaction between these factors, adolescent cannabis use and psychosis risk.

A considerable body of phenomenological research has described different ways in which the relationship of the person to the world in psychosis is affected. This literature, however, has lacked an accepted unifying theoretical model and means of quantitatively measuring these disturbances. To address this, the current article seeks to integrate a novel phenomenological model of psychosis offered by Henri Grivois, which is explicitly concerned with centrality or a person's sense of being the center of all things, with empirical research on the integrative model of metacognition, which allows for measurements of decentration or the degree to which persons can form integrated ideas about their place in their larger community. It is proposed that this literature may allow for a model of how psychotherapy can address centrality through the building of intersubjectivity and enhancing metacognition.

Summary Objective This study aimed to describe reports of psychiatric adverse drug reaction (ADR) in the spectrum of bipolar (manic features) or psychotic disorders that occurred under tumor necrosis factor alpha (TNF-α) inhibitors therapy. Methods We searched the French pharmocovigilance database for reports of psychiatric ADR in the spectrum of bipolar (manic features) or psychotic disorders during treatment with TNF-α inhibitors. Psychiatric symptoms were divided in 2 categories: (i) confirmed diagnosis of manic episode or acute psychosis and (ii) psychiatric symptoms with psychotic or manic features but not meeting sufficient criteria for diagnosis of psychosis or manic disorder. Results Overall, 9942 reports of ADR were registered in the French pharmacovigilance database with TNF-α inhibitors, including 243 reports of psychiatric ADR. Among them, we identified 41 reports of psychotic or manic disorders as define above: 9 characterised manic episodes and 32 psychiatric disorders with psychotic or manic features. TNF-α inhibitors were the only medication suspected in 23 reports (56%). The delay between starting TNF-α inhibitors treatment and onset of symptoms varied from hours to years with a median time of 40 days. Psychiatric symptoms improved in 22/23 patients in whom the TNF-α inhibitor was withdrawn. Conclusion Depressive disorders are well-known ADR of TNF-α inhibitors, but we report, here, 41 reports of psychiatric ADR diagnosed as manic or psychotic disorders or in the spectrum of bipolar or psychotic disorders with these treatments. Epidemiological studies are needed to confirm this signal.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, This work was supported by the Medical Research Council (G0901310) and the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z). This study was supported by the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London and by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust at King’s College London. Further support to EB: Mental Health Research UK’s John Grace QC award, BMA Margaret Temple grants 2016 and 2006, MRC—Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship, the NIHR Biomedical Research Centre at UCLH, and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King’s College London. Further support to co-authors: The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to CI). The BMA Margaret Temple grant 2016 to JT. A 2014 European Research Council Marie Curie award to A Díez-Revuelta. HI has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 747429. A Medical Research Council doctoral studentship to JH-S, IA-Z and AB. A Mental Health Research UK studentship to RM. VB is supported by a Wellcome Trust Seed Award in Science (200589/Z/16/Z). FWO Senior Clinical Fellowship to RvW. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organisations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Centre and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Groningen: University Medical Centre Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical centre The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en De Kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Centre Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). The Santander cohort was supported by Instituto de Salud Carlos III (PI020499, PI050427, PI060507), SENY Fundació (CI 2005-0308007), Fundacion Ramón Areces and Fundacion Marqués de Valdecilla (API07/011, API10/13). We thank Valdecilla Biobank for providing the biological PAFIP samples and associated data included in this study and for its help in the technical execution of this work; we also thank IDIVAL Neuroimaging Unit for its help in the acquisition and processing of imaging PAFIP data.

Background: This study aimed to examine whether 40-Hz auditory steady-state responses (ASSRs) are impaired in participants at clinical high-risk for psychosis (CHR-P) and predict clinical outcomes. Methods: Magnetoencephalography data were collected during a 40-Hz ASSR paradigm for a group of 116 CHR-P participants, 33 patients with first-episode psychosis (15 antipsychotic-naive), a psychosis risk–negative group (n = 38), and 49 healthy control subjects. Analysis of group differences of 40-Hz intertrial phase coherence and 40-Hz amplitude focused on right Heschl’s gyrus, superior temporal gyrus, hippocampus, and thalamus after establishing significant activations during 40-Hz ASSR stimulation. Linear regression and linear discriminant analyses were used to predict clinical outcomes in CHR-P participants, including transition to psychosis and persistence of attenuated psychotic symptoms (APSs). Results: CHR-P participants and patients with first-episode psychosis were impaired in 40-Hz amplitude in the right thalamus and hippocampus. In addition, patients with first-episode psychosis were impaired in 40-Hz amplitude in the right Heschl’s gyrus, and CHR-P participants in 40-Hz intertrial phase coherence in the right Heschl’s gyrus. The 40-Hz ASSR deficits were pronounced in CHR-P participants who later transitioned to psychosis (n = 13) or showed persistent APSs (n = 34). Importantly, both APS persistence and transition to psychosis were predicted by 40-Hz ASSR impairments, with ASSR activity in the right hippocampus, superior temporal gyrus, and middle temporal gyrus correctly classifying 69.2% individuals with nonpersistent APSs and 73.5% individuals with persistent APSs (area under the curve = 0.842), and right thalamus 40-Hz activity correctly classifying 76.9% transitioned and 53.6% nontransitioned CHR-P participants (area under the curve = 0.695). Conclusions: Our data indicate that deficits in gamma-band entrainment in the primary auditory cortex and subcortical areas constitute a potential biomarker for predicting clinical outcomes in CHR-P participants.

Highlights • The neural bases of altered emotion processing in psychosis are still unclear. • Systematic review indicated widespread activation decreases to emotion in first-episode psychosis. • Evidence in people at clinical high-risk for psychosis lacked convergence. • These findings were corroborated by image-based meta-analyses., Aberrant emotion processing is a well-established component of psychotic disorders and is already present at the first episode of psychosis (FEP). However, the role of emotion processing abnormalities in the emergence of psychosis and the underlying neurobiology remain unclear. Here, we systematically reviewed functional magnetic resonance studies that used emotion processing task paradigms in FEP patients, and in people at clinical high-risk for psychosis (CHRp). Image-based meta-analyses with Seed-based d Mapping on available studies (n = 6) were also performed. Compared to controls, FEP patients showed decreased neural responses to emotion, particularly in the amygdala and anterior cingulate cortex. There were no significant differences between CHRp subjects and controls, but a high degree of heterogeneity was identified across studies. The role of altered emotion processing in the early phase of psychosis may be clarified through more homogenous experimental designs, particularly in the CHRp population.

Metacognitive training (MCT) is a promising treatment for improving cognitive insight associated with delusional beliefs in individuals with psychotic disorders. The aim of this study was to examine potential moderators of cognitive insight in individuals with first-episode psychosis (FEP) who received either MCT or psychoeducation. The present study was based on data from a randomized control trial comparing MCT to psychoeducation. Baseline sociodemographic and clinical characteristics in a sample of 122 patients with FEP were examined as potential moderators of the self-reflectiveness and self-certainty dimensions of cognitive insight using the SPSS PROCESS macro. The only variable that moderated self-reflectiveness at the post-treatment evaluation was age of onset (b = -0.27, p = .025). The effect of MCT in reducing self-certainty was stronger in women (b = -3.26, p = .018) and in individuals with average or above average baseline self-esteem (b = -0.30, p = .007). Overall, our findings support the generalization of MCT to a variety of sociodemographic and clinical profiles. While some patient profiles may require targeted interventions such as MCT to improve cognitive insight, others may do equally as well with less demanding interventions such as a psychoeducational group.

Patients with schizophrenia are at higher risk of cardiovascular (CVS) related mortality. Close attention is being paid to the clinical utility of readily available CVS markers.A pilot one-year longitudinal study in inpatients with first-episode psychosis (FEP) was carried out to determine markers of inflammation and endothelial dysfunction (monocyte- and neutrophil-to-lymphocyte ratios) and basal blood pressure, pulse, and derived hemodynamic parameters (PP: pulse pressure; RPP: rate pressure product; and MAP: mean arterial pressure).After one year, PP and RPP increased, as did systolic blood pressure and heart rate. Systolic blood pressure, PP, total white blood cells, and neutrophils correlated with weight gain. After one year, correlations between monocyte-to-lymphocyte ratio and RPP and MAP were observed.Our study indicates worsening CVS health over the first year of treatment and emphasises the importance of early monitoring of CVS status using easily accessible parameters to prevent CVS-related mortality.Key pointsPatients with schizophrenia are at higher risk of cardiovascular mortality.The CVS risk could be evaluated using affordable, routinely available CVS markers such as monocyte- and neutrophil-to-lymphocyte ratios, blood pressure, and pulse together with the derived parameters.Our pilot study in first-episode psychosis patients indicates worsening of CVS health based on these parameters during the first year of treatment, the early monitoring of CVS status is highly relevant in clinical practice.

Objective: Existing evidence on factors associated with community treatment order placement is largely restricted to administrative data. We utilised the data from a large nationally representative sample to compare the demographic, clinical, social functioning, substance use and service utilisation profiles of people living with psychosis under community treatment orders with those who were not. Methods: Participants were grouped based on whether they had been subject to a community treatment order in the past 12 months or not. We conducted logistic regressions to examine demographic, clinical, social functioning, substance use and service utilisation profiles associated with the two groups. Results: People who had recently been subject to community treatment orders were more likely to be treated with long-acting injectable antipsychotics and lacked insight but were less likely to report suicidal ideation. They also had higher psychiatric inpatient admission rates but a lower frequency of general practitioner visits. Conclusion: People on community treatment orders in Australia may differ from those who are not under a community treatment order in their treatment needs. Resources and care provision must match the needs of this particularly vulnerable group.

BackgroundCognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients.MethodsIn total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype.ResultsProbands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype.ConclusionsCross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Background and objectives Lack of mental health resources, such as inpatient psychiatric beds, has increased frequency and duration of boarding for mental health patients presenting to U.S. emergency departments (EDs). The purpose of this study is to describe characteristics of mental health patients with an ED length of stay of one week or longer and to identify barriers to their disposition. Methods This study was conducted in an academic ED in which emergency psychiatric evaluations and care are provided by a Psychiatric Emergency Services (PES) team contained within the Department of Emergency Medicine. Prolonged boarding was defined as an ED length of stay of 7 days or more. Pediatric, adult, and geriatric mental health patients with prolonged ED boarding from January 1 to August 31, 2019 were included. This study includes prospective data collection of the boarding group and retrospective identification and data collection of a comparison group of non-barding patients over the same 8-month period to compare patient characteristics and outcomes for each group. Results Between January 1 and August 31, 2019, the PES team completed 2,745 new assessments of mental health patients, of whom 39 met criteria for prolonged ED boarding. The following characteristics were associated with boarding: child (8%), male (64%), having Medicaid (49%) or both Medicaid and Medicare (18%), and having either a neurodevelopmental (15%) or neurocognitive disorder (15%) with a median stay of 18 days. Barriers to discharge included being declined from all state inpatient psychiatric hospitals (69%), declined from community living environments (21%), or declined from both (10%). The most common ED non-boarding patients were: Caucasian (64%), have a diagnosis of unspecified mental disorder (including suicidal ideation) or other specified mental disorder (59%) and have private insurance (42%) with a median stay of 1 day. Conclusion In this study of mental health patients with prolonged ED stays, the primary barrier to disposition was the lack of patient acceptance to inpatient psychiatric hospitals, community settings, or other housing. Early identification of potential prolonged boarding, quality treatment and care for those patients, and effective case management, may resolve the ongoing challenges of boarding within the ED.

Objectives In nursing homes (NHs), 30% to 60% of patients experience daily pain and >80% have dementia. This can lead to neuropsychiatric symptoms, including psychosis symptoms such as delusion. We investigated if there was a relationship between pain and psychosis symptoms over time. We also aimed to investigate the effect of a multicomponent intervention (COSMOS) on pain, psychosis symptoms, and analgesic prescription. Design COSMOS is a cluster-randomized, single blinded, controlled trial. Each NH unit was defined as a cluster and randomized to either the COSMOS intervention or care as usual. The COSMOS intervention is a multicomponent intervention, consisting of staff training in communication, pain treatment, medication review, organization of activities, and safety. The intervention lasted for 4 months with a follow-up at month 9. Setting and Participants Sixty-seven units from 33 Norwegian NHs in 8 municipalities. The study included 723 patients aged ≥65 years, residing at the NH ≥2 weeks before inclusion. Patients with a life expectancy

Sociocultural context seems to influence the epidemiology, phenotype, treatment, and course of psychosis. However, data from low- and middle-income countries is sparse. This research is part of a multidisciplinary and multimethod study on possible mental disturbances, including hallucinations, among (apprentice) traditional health practitioners (THPs) who have experienced the “ancestral calling to become a THP” in rural KwaZulu-Natal, South Africa. The aim of the current article is to examine whether the calling-related experiences can be assessed according to a psychiatric taxonomy. We included individuals who were identified with the calling and who were undergoing training to become a THP ( ukuthwasa). IsiZulu-speaking formal mental health practitioners conducted thorough psychiatric interviews that measured psychological experiences with and without distress using the Community Assessment of Psychic Experiences, and psychiatric symptoms and disorders using the Schedule for Clinical Assessment in Neuropsychiatry. Of the 48 individuals who participated, 92% had psychotic experiences (PE), causing distress in 75%; and 23% met DSM-5 criteria for an unspecified psychotic disorder (15%) or mood disorder (8%). In conclusion, in rural KwaZulu-Natal, the ancestral calling may resemble phenomena that psychiatry would understand in the context of psychosis, ranging from subclinical PE to clinical psychotic disorder. Ukuthwasa might have a beneficial influence on the course of psychotic symptoms in some individuals, potentially because it reduces stigma and promotes recovery. Further multidisciplinary research is needed to investigate the psychopathology of the apprentice THPs and the underlying processes of ukuthwasa.

Background/purpose In 2017, Long-Fa Temple, an illegal religious asylum in Taiwan, was forced to shut down. Hundreds of chronic mentally ill patients were incarcerated there but provided with no modern psychiatric treatment. This study investigated the effectiveness of providing psychiatric intervention for patients subsequently transferred from Long-Fa Temple to a medical center. Methods In total, 88 patients (mean age: 57.2 years, 52.3% male) who had been incarcerated at Long-Fa Temple were transferred to a southern medical center. The patients underwent comprehensive biological, psychological, and social treatment for 18 months. The patients were evaluated once a month in terms of their psychotic symptoms, self-care, nutrition status, cognitive function, occupational function, and family function. Results Regarding the patients' length of stay, 18.2% were incarcerated in Long-Fa Temple for less than 10 years, 21.6% for 10–20 years, and 60.2% for more than 20 years. In terms of psychiatric diagnosis, 98.9% of the patients had been diagnosed with a schizophrenia spectrum disorder. During the 18-month treatment period, negative symptoms decreased significantly, while the patients’ self-care ability, nutrition status, cognition, occupational function, and family function all significantly improved over time. Patients who had been incarcerated for less than 10 years demonstrated better improvements in psychotic symptoms, self-care, nutrition status, and cognitive function. Conclusion Contemporary psychiatric intervention is beneficial for chronically untreated mentally ill patients, and the patients who had a shorter duration of illness had a better reserve of recovery. These findings can serve as an important reference for psychiatric intervention in developing countries.

The historical association between respiratory infections and neuropsychiatric symptoms dates back centuries, with more recent literature highlighting a link between viral infections and schizophrenia. Maternal influenza infection during pregnancy has been associated with the development of schizophrenia in offspring. Viral infections in neonates, children, and adolescents have also been associated with later development of schizophrenia. Neuroinvasive and/or systemic infections are thought to increase risk for psychopathology via inflammatory mechanisms, particularly when exposure occurs during critical neurodevelopmental windows. Several human coronaviruses (HCoVs) have been associated with psychotic disorders and increasing reports of the neuropsychiatric manifestations of COVID-19 suggest it has neuroinvasive properties similar to those of other HCoVs. These properties, in conjunction with its ability to generate a massive inflammatory response, suggest that COVID-19 may also contribute to future psychopathology. This review will summarize the psychopathogenic mechanisms of viral infections and discuss the neuroinvasive and inflammatory properties of COVID-19 that could contribute to the development of psychotic disorders, with a focus on in utero, neonatal, and childhood exposure.

The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EUGEI); The Spanish sample was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024) (...), Velthorst, E., Mollon, J., Murray, R.M., de Haan, L., Germeys, I.M., Glahn, D.C., Arango, C., van der Ven, E., Di Forti, M., Bernardo, M., Guloksuz, S., Delespaul, P., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., García-Portilla, M.P., Santos, J.L., Jiménez-López, E., Sanjuan, J., Aguilar, E.J., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Atbaşoğlu, C., Saka, M.C., Üçok, A., Alptekin, K., Akdede, B., Binbay, T., Altınyazar, V., Ulaş, H., Yalınçetin, B., Gümüş-Akay, G., Beyaz, B.C., Soygür, H., Cankurtaran, E.Ş., Kaymak, S.U., Maric, N.P., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Del-Ben, C.M., Ferraro, L., Gayer-Anderson, C., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P.R., Morgan, C., Quattrone, D., Menchetti, M., Selten, J.-P., Szöke, A., Tarricone, I., Tortelli, A., McGuire, P., Valmaggia, L., Kempton, M.J., van der Gaag, M., Riecher-Rössler, A., Bressan, R.A., Barrantes-Vidal, N., Nelson, B., McGorry, P., Pantelis, C., Krebs, M.-O., Ruhrmann, S., Sachs, G., Rutten, B.P.F., van Os, J., Alizadeh, B.Z., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., van Beveren, N.J., Luykx, J.J., Cahn, W., Simons, C.J.P., Kahn, R.S., Schirmbeck, F., van Winkel, R., Calem, M., Tognin, S., Modinos, G., Pisani, S., Kraan, T.C., van Dam, D.S., Burger, N., Amminger, G.P., Politis, A., Goodall, J., Borgwardt, S., Studerus, E., Gadelha, A., Brietzke, E., Asevedo, G., Asevedo, E., Zugman, A., Domínguez-Martínez, T., Monsonet, M., Cristóbal-Narváez, P., Racioppi, A., Kwapil, T.R., Kazes, M., Daban, C., Bourgin, J., Gay, O., Mam-Lam-Fook, C., Nordholm, D., Rander, L., Krakauer, K., Glenthøj, L.B., Glenthøj, B., Gebhard, D., Arnhold, J., Klosterkötter, J., Lasser, I., Winklbaur, B., Reichenberg, A., EU-GEI High Risk Study

Objective Schizophrenia is increasingly understood as an interactive network of disturbances in different elements of self-awareness. In this study we have examined the relationship between disturbances in two forms of awareness: cognitive insight and clinical insight by exploring whether their relationship is mediated by a third form of larger awareness: metacognition. Methods Participants were 41 outpatients with schizophrenia and 37 outpatients with early episode psychosis gathered in Moscow, Russia. Metacognition was assessed with the Metacognition Assessment Scale - Abbreviated. Verbal memory and positive symptoms were assessed for use as additional mediators. Results Mediation analyses revealed that after accounting for the effects of positive symptoms and verbal memory, the relationship between the self-reflection domain of cognitive insight and clinical insight was significantly mediated by overall metacognitive capacity. Further, positive symptoms were a significant mediator between the cognitive insight self-reflection domain and clinical insight. Neither metacognition nor positive symptoms or verbal memory were found to mediate the relationship of the cognitive insight domain of self-certainty with clinical insight. Conclusions Decrements in some forms of ability to reflect upon one's thinking may reduce the ability to form complex and integrated ideas of oneself and others, leading to less coherent and complete accounts of the experience of schizophrenia.

BACKGROUND: In the United States (US), 61% of all suicide cases may involve firearms, and some evidence suggests that mental disorders may play a role in suicide by firearm. We performed the first systematic review and meta-analyses to investigate: (i) whether mental disorders are associated with suicide by firearm, and (ii) whether the risk of using a firearm compared with alternative means is associated with higher levels of suicide in individuals with a mental disorder\ud \ud METHODS AND FINDINGS: We searched twelve databases from inception to the 24th of May 2020. We retrieved 22 observational studies conducted in the US. Random-effects meta-analyses showed individuals who had a diagnosis of a mental disorder had lower odds (odds ratios (OR)= 0.50, 95% CI: 0.36 to 0.69; I2=100 (95% CI: 87 to 100%), of dying by suicide with a firearm than those who did not have a diagnosis of a mental disorder. Secondary analysis showed that decedents who had a mental health diagnosis resulted in lower odds of dying by suicide by using firearms than using other means\ud \ud LIMITATIONS: Risk of bias revealed a heterogeneous and poor definition of mental disorders as well as lack of control for potential demographic confounding factors. In the meta-analyses, studies were combined in the same analytic sample as 77% of these studies did not specify the type of mental disorder\ud \ud CONCLUSION: While our results seem to suggest that having a mental disorder may not be consistently associated with the odds of dying by suicide using a firearm, the presence of substantial heterogeneity and high risk of bias precludes any firm conclusions.

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.

Objectives Patients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification. Methods In total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA). Results All HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions. Conclusions HRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.

COVID-19 has led to a great deal of general suffering and an increased prevalence of psychiatric illness worldwide. Within the area of psychosis-risk syndromes, a highly heterogeneous clinical population, the picture is quite nuanced as the social restrictions resulting from the pandemic have reduced stress for some and increased it for others. Further, a number of pandemic-related societal and cultural changes have obfuscated the diagnostic and treatment landscape in this area as well. In this opinion article, we describe several prototypical cases, representative of presentations seen in our clinical high-risk (CHR) research programs. The cases highlight considerable clinical variability and, in addition, speak to the current complexities faced by diagnosticians and treatment providers. In addition to discussing these issues, this piece introduces potential solutions highlighting the promise of incorporating data-driven strategies to identify more homogenous CHR subtypes and employ precision medicine.

Recent review articles provided an extensive collection of studies covering many aspects of format thought disorders (FTD) among their epidemiology and phenomenology, their neurobiological underpinnings, genetics as well as their transdiagnostic prevalence. However, less attention has been paid to the association of FTD with neurocognitive and functioning deficits in the early stages of evolving psychosis. Therefore, this systematic review aims to investigate the state of the art regarding the association between FTD, neurocognition and functioning in the early stages of evolving psychotic disorders in adolescents and young adults, by following the PRISMA flowchart. A total of 106 studies were screened. We included 8 studies due to their reports of associations between FTD measures and functioning outcomes measured with different scales and 7 studies due to their reports of associations between FTD measures and neurocognition. In summary, the main findings of the included studies for functioning outcomes showed that FTD severity predicted poor social functioning, unemployment, relapses, re-hospitalisations, whereas the main findings of the included studies for neurocognition showed correlations between attentional deficits, executive functions and FTD, and highlighted the predictive potential of executive dysfunctions for sustained FTD. Further studies in upcoming years taking advantage of the acceleration in computational psychiatry would allow researchers to re-investigate the clinical importance of FTD and their role in the transition from at-risk to full-blown psychosis conditions. Employing automated computer-assisted diagnostic tools in the early stages of psychosis might open new avenues to develop targeted neuropsychotherapeutics specific to FTD.

The study of hallucinations across multiple senses in psychosis has garnered renewed interest. Recent studies have adopted the term multimodal hallucinations to describe these experiences, yet some appear to be investigating a different, but related, phenomenon. In the current paper, we suggest use of the terms multimodal hallucinations and multisensory hallucinations to categorise distinct events that involve unusual sensory experiences across multiple domains. We propose that the constructs of temporality and relatedness are critical to delineating these experiences, where multimodal hallucinations refer to hallucinations in two or more sensory modes occurring concurrently in time and/or with significant thematic overlaps. Multisensory hallucinations conversely denote similar multisensory experiences, but with no temporal or relatedness constraints. This is accompanied by a decision-making framework for identifying whether a set of unusual perceptual experiences constitutes multimodal hallucinations or otherwise. We conclude by suggesting several priorities for future research, including empirical validation of our proposed model, further investigation of phenomenology, developing appropriate assessment tools and investigating underlying cognitive and other aetiological mechanisms.