Background The etiology of schizophrenia involves both biological and environmental risk factors. Studying childhood trauma in disorders along the schizophrenia spectrum, including schizotypal personality disorder (SPD), can inform early risk and protective factors for psychosis. However, no study has directly compared childhood trauma between SPD and schizophrenia. Study Design One hundred twenty-four

Background Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified. Methods We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of polygenic risk scores for schizophrenia, bipolar disorder

Background and Hypothesis Inflammatory proteins are implicated in psychiatric disorders, but the causality and underlying mechanisms remain unclear. Study Design We conducted bidirectional Mendelian randomization (MR) using genetic variants from genome-wide association studies (GWAS) for 91 inflammatory proteins (N = 14 824) and 11 psychiatric disorders (N = 9725 to 1 035 760). The primary analysis

Background Overweight and obesity are highly prevalent in people with severe mental illness (SMI). Antipsychotic-induced weight gain (AIWG) is one of the most commonly reported and distressing side effects of treatment and people living with SMI place a high value on the avoidance of this side effect. Metformin is the most effective pharmacological intervention studied for the prevention of AIWG yet

Background and Hypotheses The causes of schizophrenia remain unclear, and research has been hindered by the lack of quantifiable standards. However, magnetic resonance imaging (MRI) is addressing these challenges, revealing critical neurobiological details and emphasizing its importance in both evaluation and treatment. Study Design First, we reviewed the progress of research on structural MRI (sMRI)

Background The association of social and clinical indicators with employment, disability, and health outcomes among individuals with severe mental illnesses (SMI) remains unclear. Existing evidence primarily comes from smaller cohort studies limited by shorter follow-up and high attrition, or registry-based research, which lacks information on important social determinants. Study Design We utilized

Background and Hypothesis Schizophrenia is a complex disorder thought to have neurodevelopmental and neurodegenerative aspects. Optical coherence tomography (OCT) measurements of schizophrenia patients revealed that the retinal layers of these patients were thinner than those of healthy controls. This study aimed to examine retinal changes in first-episode psychosis patients treated with electroconvulsive

Background and Hypothesis Duration of untreated psychosis (DUP) has been linked to worse mental health outcomes in psychotic disorders. We meta-analytically studied the relationship between “long” vs. “short” DUP and mental health outcomes. Study Design This PRISMA/MOOSE-compliant meta-analysis searched for nonoverlapping individual studies from database inception until November 01, 2023, reporting

Background and Hypothesis Understanding perceptual alterations in mental disorders can help uncover neural and computational anomalies. In schizophrenia, perceptual alterations have been reported for many visual features, including a deficit in contrast sensitivity, a key measure of visual function. The evidence supporting this deficit, however, has not been comprehensively synthesized. Study Design

Background and Hypothesis Since a prior systematic review and meta-analysis reported an association between psychotic experiences (PEs) and suicidal thoughts and behaviors, a large number of new studies have been published on the topic, including several novel studies on the association between PEs and transition from suicidal ideation to attempt. Study Design Two authors independently searched PubMed

Background and Hypothesis The complex immune-brain interactions and the regulatory role of mitochondria in the immune response suggest that mitochondrial damage reported in schizophrenia (SZ) may be related to abnormalities observed in immune and brain functions. Study Design Mitochondrial DNA copy number (mtDNA CN), a biomarker of mitochondrial function, was assessed in peripheral blood leukocytes

Background and Hypothesis Studying individuals at Clinical High Risk (CHR) for psychosis provides an opportunity to examine protective factors that predict resilient outcomes. Here, we present a model for the study of protective factors in CHR participants at the very highest risk for psychotic conversion based on the Psychosis Risk Calculator. Study Design CHR participants (N = 572) from NAPLS3 were

Background and Hypothesis The number of clinical efficacy trials of Cognitive Remediation (CR), a behavioral intervention consisting of cognitive task practice and/or strategy training to improve cognitive skills in schizophrenia, has increased substantially over the past 25 years. While recent reviews have highlighted the effects of CR on cognition and function, CR effects on negative symptoms remain

Background and Hypothesis Angiogenesis triggered by inflammation increases BBB permeability and facilitates macrophage transmigration. In the midbrain, we have discovered molecular alterations related to the blood-brain barrier (BBB), including endothelial cell changes associated with macrophage diapedesis, in neuroinflammatory schizophrenia and bipolar disorder, but changes in angiogenesis are yet

Background and Hypothesis Sex differences in psychosis are reported across the psychosis spectrum, including in subclinical stages. An important factor in understanding these variations is the subjective experience of everyday social interactions (SI). We investigated whether the presence of psychotic experiences (PEs), as well as associated distress, differs between men and women. We focused on the

Background Negative symptoms of schizophrenia are correlated with reduction of normal function and lower quality of life. They were newly defined by the NIMH-MATRICS Consensus in 2005, dividing the rating tools to assess them into first-generation scales, developed before the Consensus, and second-generation scales, based on the recently introduced definitions. Methods The COnsensus-based Standards

Background and Hypothesis Individuals with schizophrenia have less priors than controls, meaning they rely less upon their prior experiences to interpret the current stimuli. These differences in priors are expected to show as higher alternation rates in bistable perception tasks like the Structure-from-Motion (SfM) paradigm. In this paradigm, continuously moving dots in two dimensions are perceived

Background and Hypothesis Psychotic disorders (PDs) have huge personal and societal impact, and efforts to improve outcomes in patients are continuously needed. Environmental risk factors (ERFs), especially modifiable risk factors, are important to study because they pose a target for intervention and prevention. No studies have investigated ERFs, cognition, and psychotic symptoms together in a network

Background and Hypothesis Numerous studies have found that being born or raised in urban environments increases the odds of developing psychosis in Northern and Western Europe. However, available research from Southern Europe, Latin America, and Asia has reported null results. A limitation in most studies to date is the inadequate characterization of urban and rural life components that may contribute

Background and Hypothesis The onset of schizophrenia occurs after the age of 40 in up to 20% of cases. We aim to depict risk factors for first-episode psychosis after the age of 40 by comparing late-onset psychosis (LOP) patients to healthy age-matched controls. Study Design In this case-control study using electronic health records, 142 individuals aged 40–65 years with an encounter for a first episode

Background Evidence regarding schizophrenia relapse following acute electroconvulsive therapy (ECT) is sparse compared with that for depression, and we have no clear consensus on relapse proportions. We aimed to provide longitudinal information on schizophrenia relapse following acute ECT. Study Design This systematic review and meta-analysis included randomised controlled trials (RCTs) and observational

Subtle distortions of the experience of lived space have long been associated with schizophrenia. Although a body-centric transformation of space is considered an essential component of anomalous subjective experience in schizophrenia, its impact on the 2 major body-centric spatial constructs, that is, personal space (PS) and peripersonal space (PPS), is still not clear. This systematic review and

Background Emotion processing (EP) is impaired in individuals with psychosis and associated with social functioning; however, it is unclear how symptoms fit into this relationship. The aim of this systematic review and meta-analysis was to examine interrelationships between EP, symptoms, and social functioning, test whether different symptom domains mediate the relationship between EP and social functioning

Background Digital health interventions (DHIs) may enable low cost, scalable improvements in the quality of care for adults with schizophrenia. Given the fast-growing number of studies using these tools, this review aimed to assess the efficacy and feasibility of randomized controlled trials (RCTs) of DHIs among people with schizophrenia, focusing on human support. Design A systematic search of PubMed

Anhedonia refers to the diminished ability to experience pleasure, and is a core feature of schizophrenia (SCZ). The neurocognitive and neural correlates of anhedonia remain elusive. Based on several influential theoretical models for negative symptoms, this selective review proposed four important neurocognitive domains, which may unveil the neurobiological mechanisms of anhedonia. The authors critically

Background and Hypothesis There has been a century-long debate about whether the major psychoses (eg, bipolar disorder, schizophrenia, and schizoaffective disorder) are one disorder with various manifestations or different disease entities. Traditional approaches using dimensional models have not provided decisive findings. Here, we address this question by examining the network constellation of affective

Background The ultimate goal of successful schizophrenia treatment is not just to alleviate psychotic symptoms, but also to reduce distress and achieve subjective well-being (SWB). We aimed to identify the determinants of SWB and their interrelationships in schizophrenia. Methods Data were obtained from 637 patients with schizophrenia enrolled in multicenter, open-label, non-comparative clinical trials

Background Electroencephalography (EEG) is a noninvasive, cost-effective, and robust tool, which directly measures in vivo neuronal mass activity with high temporal resolution. Combined with state-of-the-art machine learning (ML) techniques, EEG recordings could potentially yield in silico biomarkers of severe mental disorders. Hypothesis Pathological and physiological aging processes influence the

Background and Hypothesis Schizophrenia is associated with a decreased pursuit of risky rewards during uncertain-risk decision-making. However, putative mechanisms subserving this disadvantageous risky reward pursuit, such as contributions of cognition and relevant traits, remain poorly understood. Study Design Participants (30 schizophrenia/schizoaffective disorder [SZ]; 30 comparison participants

Background Since the late 1990s, there has been a worldwide surge of scientific interest in the pre-psychotic phase, resulting in the introduction of several clinical tools for early detection. The predictive accuracy of these tools has been limited, motivating the need for methodological and perspectival improvements. The EASE manual supports systematic assessment of anomalous self-experience, and

Studies of individuals with chronic, untreated schizophrenia (CUS) can provide important insights into the natural course of schizophrenia and how antipsychotic pharmacotherapy affects neurobiological aspects of illness course and progression. We systematically review 17 studies on the neuroimaging, cognitive, and epidemiological aspects of CUS individuals. These studies were conducted at the Shanghai

Background and Hypothesis While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited. Study Design To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We utilized the most

Background and Hypothesis Shame has been linked to the experience of psychosis, with implications for clinical outcomes, however, a meta-analysis of the relationship has not yet been conducted. This systematic review and meta-analysis aimed to examine the strength of the association between shame and psychosis, and any variations between clinical and non-clinical populations and shame type (internal

Background and Hypothesis The human visual system streamlines visual processing by suppressing responses to textures that are similar to their surrounding context. Surround suppression is weaker in individuals with schizophrenia (ISZ); this altered use of visuospatial context may relate to the characteristic visual distortions they experience. Study Design To understand atypical surround suppression

Background and Hypothesis Social cognitive impairments are central to psychosis, including lower severity psychosis-like experiences (PLEs). Nonetheless, progress has been hindered by social cognition’s poorly defined factor structure, as well as limited work examining the specificity of social cognitive impairment to psychosis. The present study examined how PLEs relate to social cognition in the

Background and Hypothesis Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition

Background Cognitive impairment associated with schizophrenia (CIAS) negatively impacts daily functioning, quality of life, and recovery, yet effective pharmacotherapies and practical assessments for clinical practice are lacking. Despite the pivotal progress made with establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery

Background and Hypothesis: The Cognitive Model of Negative Symptoms is a prominent model that posits that defeatist performance beliefs (DPB) are a key psychological mechanism underlying negative symptoms in those with schizophrenia (SZ). However, the ecological validity of the model has not been established, and temporally specific evaluations of the model’s hypotheses have not been conducted. This

Background and Hypothesis The time taken for an individual who is at the clinical high-risk (CHR) stage to transition to full-blown psychosis may vary from months to years. This temporal aspect, known as the timeframe for conversion to psychosis (TCP), is a crucial but relatively underexplored dimension of psychosis development. Study Design The sample consisted of 145 individuals with CHR who completed

Background and Hypothesis Schizophrenia is a severe mental disorder that has a significant impact on quality of life (QOL). Measuring QOL can offer insights into treatment efficacy and areas of intervention, highlighting the importance of valid tools assessing QOL in people with schizophrenia. Study Design We employed the COSMIN systematic review guideline to assess the psychometric properties of the

Background and Hypothesis To clarify, in a large, representative, longitudinal sample, the rate and predictors of diagnostic conversion from Bipolar Disorder (BD) to Schizophrenia (SZ) and from SZ→BD. Design From individuals born in Sweden 1950–1995 and living there in 1970 or later, we identified at least one initial diagnoses of SZ (n = 8449) and BD (n = 8438) followed for a minimum of 10 and a mean

Background and Hypothesis Pregnant women with persistent schizophrenia and related disorders may require ongoing antipsychotic treatment, including clozapine. However, the potential risks of using clozapine during pregnancy and the postnatal period remain uncertain. Study Design We conducted a nested case-control study using the National Register of Antipsychotic Medication in Pregnancy (NRAMP) database

Background Discharge from early psychosis intervention is a critical stage of treatment that may occur for a variety of reasons. This study characterizes reasons for discharge among participants in early psychosis intervention programs participating in the Early Psychosis Intervention Network (EPINET) which comprises >100 programs in the United States organized under 8 academic hubs. Study Design We

Background and Hypothesis Recovering from a first psychosis is a highly individual process and requires the person to make sense of their experiences. Clinicians, in turn, need to comprehend these first-person perspectives, creating a mutual sense-making dynamic. Antipsychotic medication is a substantial part of psychosis treatment. Providing insight in the lived experience of recovery with antipsychotics

Background and Hypothesis Zinc finger protein 804A (ZNF804A) was the first genome-wide associated susceptibility gene for schizophrenia (SCZ) and played an essential role in the pathophysiology of SCZ by influencing neurodevelopment regulation, neurite outgrowth, synaptic plasticity, and RNA translational control; however, the exact molecular mechanism remains unclear. Study Design A nervous-system-specific

Background Various neurocognitive models explore perceptual distortions and hallucinations in schizophrenia and the general population. A variant of predictive coding account suggests that strong priors, like cognitive expectancy, may influence perception. This study examines if stronger cognitive expectancies result in more auditory false percepts in clinical and healthy control groups, investigates

Background and Hypothesis Schizophrenia (SZ) is characterized by significant cognitive and behavioral disruptions. Neuroimaging techniques, particularly magnetic resonance imaging (MRI), have been widely utilized to investigate biomarkers of SZ, distinguish SZ from healthy conditions or other mental disorders, and explore biotypes within SZ or across SZ and other mental disorders, which aim to promote

Background and Hypothesis In response to Health Canada’s March 2020 directive, patients on clozapine for over 12 months were allowed to extend hematological testing intervals from 4 to 8 weeks during the COVID-19 pandemic. We hypothesized that this change would not affect the timely detection of hematological abnormalities in patients with severe mental illness. Study Design A chart review was conducted

Background Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Design Structural magnetic resonance imaging

Background and Hypothesis Schizotypy is a useful and unifying construct for examining the etiology, development, and expression of schizophrenia-spectrum psychopathology. The positive, negative, and disorganized schizotypy dimensions are associated with distinct patterns of schizophrenia-spectrum symptoms and impairment. Furthermore, they are differentiated by mean levels of psychotic-like, suspicious

For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute’s ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives—Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience

Background and Hypothesis Substance use is highly prevalent among people with schizophrenia (SCZ) and related disorders, however, there is no broad-spectrum pharmacotherapy that concurrently addresses both addiction and psychotic symptoms. Psychosocial (PS) interventions, which have yielded promising results in treating psychosis and substance dependence separately, demonstrate potential but have not

Background and Hypothesis For a long time, it was proposed that schizophrenia (SCZ) patients rely more on sensory input and less on prior information, potentially leading to reduced serial dependence—ie, a reduced influence of prior stimuli in perceptual tasks. However, existing evidence is constrained to a few paradigms, and whether reduced serial dependence reflects a general characteristic of the

Background and Hypothesis Up to 43% of people with schizophrenia have a lifetime cannabis use disorder (CUD). Tetrahydrocannabinol (THC) has been shown to exacerbate psychosis in a dose-dependent manner, but little research has assessed its effects on schizophrenia and co-occurring CUD (SCZ-CUD). In this double-dummy, placebo-controlled trial (total n = 130), we hypothesized that a modest dose of THC

Background and Hypothesis Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets. Study Design To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS)

Background The ganglionic eminences (GE) are fetal-specific structures that give rise to gamma-aminobutyric acid (GABA)- and acetylcholine-releasing neurons of the forebrain. Given the evidence for GABAergic, cholinergic, and neurodevelopmental disturbances in schizophrenia, we tested the potential involvement of GE neuron development in mediating genetic risk for the condition. Study Design We combined

Background Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear. Design We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment

Background and Hypothesis The high co-occurrence of tobacco smoking in patients with schizophrenia spectrum disorders (SSD) poses a serious health concern, linked to increased mortality and worse clinical outcomes. The mechanisms underlying this co-occurrence are not fully understood. Study Design Addressing the need for a comprehensive overview of the impact of tobacco use on SSD neurobiology, we

Background Sensory suppression occurs when hearing one’s self-generated voice, as opposed to passively listening to one’s own voice. Quality changes in sensory feedback to the self-generated voice can increase attentional control. These changes affect the self-other voice distinction and might lead to hearing voices in the absence of an external source (ie, auditory verbal hallucinations). However

Background and Hypothesis Brain development/aging is not uniform across individuals,spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging