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

Background Schizophrenia, a multifaceted psychiatric disorder characterized by functional dysconnectivity, poses significant challenges in clinical practice. This study explores the potential of functional connectivity (FC)-based searchlight multivariate pattern analysis (CBS-MVPA) to discriminate between schizophrenia patients and healthy controls while also predicting clinical variables. Study Design

Background During the last decades, an abundance of studies has investigated childhood adversity in relation to psychosis. This systematic review critically examines the methodologies employed to investigate childhood adversity in psychosis over the past decade, including operational definitions, measurement tools and characteristics, and psychometric properties of instruments used in these studies

Background and Hypothesis This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. Study Design This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse

Background and Hypothesis There is mounting evidence that cardiac interoception, the perception of one’s heartbeat, is central to affective experiences. It has been proposed that symptoms of psychosis could arise from interoceptive dysfunction. Here we hypothesized that people with psychotic disorders would have a specific impairment in cardiac interoception, over and above broader perceptual deficits

Background and Hypothesis Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. Study

In our previous paper on the Future of Cognitive Remediation published more than 10 years ago, we envisaged an imminent and wide implementation of cognitive remediation therapies into mental health services. This optimism was misplaced. Despite evidence of the benefits, costs, and savings of this intervention, access is still sparse. The therapy has made its way into some treatment guidance, but these

Background and Hypothesis This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals. Study Design The review

Background and Hypothesis The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic

Background and Hypothesis Psychosis-associated diagnostic codes are increasingly being utilized as case definitions for electronic health record (EHR)-based algorithms to predict and detect psychosis. However, data on the validity of psychosis-related diagnostic codes is limited. We evaluated the positive predictive value (PPV) of International Classification of Diseases (ICD) codes for psychosis.

Background and Hypothesis Recent studies show that, despite providing some relief, feedback about being at risk for psychosis often triggers negative emotional reactions. Inspired by Tversky and Kahneman’s (1981) work on the framing effect and medical framings that favors positive framing like “life-threatening” over “high-risk for death,” this study tested the hypothesis that positive reframing of

Background and hypothesis Psychotic-like experiences (PLEs) are prevalent in the general population and, because they represent a lower end of the psychosis vulnerability spectrum, may be useful in informing mechanistic understanding. Although it is well-understood that motor signs characterize formal psychotic disorders, the developmental trajectory of these features and their relationships with PLEs

Background Diagnostic criteria for mental disorders are subject to change. This is particularly true for schizophrenia, whose diagnostic criteria in the current DSM-5 bear little resemblance to what Kraepelin once named “dementia praecox” and Bleuler termed “the schizophrenias.” The present study reports results from a survey of experts on two core topics of schizophrenia: (a) whether subsequent editions

Background and Hypothesis The ClozaGene Study is a nationwide cohort of adults who have been treated with clozapine. While clozapine is indicated in the management of treatment-resistant schizophrenia, it is associated with a considerable adverse drug reaction (ADR) burden, and not all patients achieve adequate symptomatic response. The current study focuses on self-reported experiences of clozapine

Background and Hypothesis Cognitive impairment is a core feature of schizophrenia that worsens with aging and interferes with quality of life. Recent work identifies sleep as an actionable target to alleviate cognitive deficits. Cardinal non-rapid eye movement (NREM) sleep oscillations such as sleep spindles and slow oscillations are critical for cognition. People living with schizophrenia (PLWS) and

Background and Hypothesis Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the between-person level, which has constrained analyses

Background and Hypothesis Exposure to childhood maltreatment—a risk factor for psychosis is associated with paranoia—may impact one’s beliefs about the world and how beliefs are updated. We hypothesized that increased exposure to childhood maltreatment is related to volatility-related belief updating, specifically higher expectations of volatility, and that these relationships are strongest for threat-related

Background and Hypothesis The World Health Organization’s (WHOs) Mental Health Gap Action Programme (mhGAP) aims to improve healthcare for mental, neurological, and substance use disorders in nonspecialized settings, with a focus on low- and middle-income countries (LMICs). mhGAP includes guidelines for the treatment of psychoses (including schizophrenia), which were recently updated in 2023. The complexity

Background Negative symptoms in schizophrenia (SZ), such as apathy and diminished expression, have limited treatments and significantly impact daily life. Our study focuses on the functional division of the striatum: limbic—motivation and reward, associative—cognition, and sensorimotor—sensory and motor processing, aiming to identify potential biomarkers for negative symptoms. Study Design This longitudinal

Background and hypothesis Breast cancer is more prevalent in women with severe mental illness than in the general population, and use of prolactin-increasing antipsychotics may be a contributing factor. Study design A nested case–control study was conducted using the Swedish nationwide registers (inpatient/outpatient care, sickness absence, disability pension, prescribed drugs, cancers). All women

Background Heterogeneity in the etiology, pathophysiology, and clinical features of schizophrenia challenges clinicians and researchers. A helpful approach could be stratifying patients according to the presence or absence of clinical features of the deficit syndrome (DS). DS is characterized by enduring and primary negative symptoms, a clinically less heterogeneous subtype of the illness, and patients

Background and Hypothesis Parkinsonism, psychomotor slowing, negative and depressive symptoms show evident phenomenological similarities across different mental disorders. However, the extent to which they interact with each other is currently unclear. Here, we hypothesized that parkinsonism is an independent motor abnormality showing limited associations with psychomotor slowing, negative and depressive

Background Traumatic brain injury (TBI) is linked with an increased risk of schizophrenia and other non-mood psychotic disorders (psychotic disorders), but the prevalence and contributing factors of these psychiatric conditions post-TBI remain unclear. This study explores this link to identify key risk factors in TBI patients. Methods We used the 2017 National Inpatient Sample dataset. Patients with

Background and Hypothesis The synaptic pruning hypothesis posits that schizophrenia (SCZ) and autism spectrum disorder (ASD) may represent opposite ends of neurodevelopmental disorders: individuals with ASD exhibit an overabundance of synapses and connections while SCZ was characterized by excessive pruning of synapses and a reduction. Given the strong genetic predisposition of both disorders, we propose

Background and Hypothesis The current study investigated the extent to which changes in attentional control contribute to performance on a visual perceptual discrimination task, on a trial-by-trial basis in a transdiagnostic clinical sample. Study Design Participants with schizophrenia (SZ; N = 58), bipolar disorder (N = 42), major depression disorder (N = 51), and psychiatrically healthy controls

Background and Hypothesis Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system’s function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical