Background and Hypothesis The objective of this study was to identify documented negative symptoms of schizophrenia using natural language processing (NLP) and to characterize treatment patterns, healthcare resource utilization (HCRU), and costs among this patient population. Study Design This US retrospective cohort study used electronic health records (EHR) linked to administrative claims data from

Background and Hypothesis Little is understood about whether the high reported prevalence of dementia in people with psychosis reflects impairment present at psychosis onset. We hypothesized that relying on longitudinal data would help to distinguish stable deficits associated with psychotic disorders from subsequent decline. Study Design We prospectively assessed the Clinical Dementia Rating (CDR)

Background and Hypothesis The brain age gap (BAG) quantifies the difference between predicted brain age and chronological age. Prior research implicates higher BAG in psychotic disorders, suggesting accelerated brain aging. We hypothesized distinct brain aging profiles among biological subtypes of psychosis and intermediate BAG in their relatives. Study Design Brain age gap values were quantified in

Background and Hypothesis Schizophrenia is a devastating psychiatric disorder characterized by positive (eg, hallucinations) and negative (eg, reduced motivation) symptoms, and cognitive deficits. Chronic gastrointestinal tract issues exist as comorbid symptoms of schizophrenia. Recent findings indicate the involvement of the microorganisms that inhabit the gut, the microbiota (and the broader microbiome

Background Schizophrenia is associated with substantial physical and psychiatric comorbidities that increase the risk of severe outcomes in COVID-19 infection. However, few studies have examined the differences in care and outcomes among people with schizophrenia throughout the pandemic. We hypothesized that rates of in-hospital mortality, admission to the intensive care unit (ICU), and length of stay

Background and Hypothesis Pregnant women with schizophrenia are more likely to discontinue treatment, which could trigger a relapse of symptoms. However, data on patterns and risk factors related to antipsychotic discontinuation and re-initiation in Asian pregnant women are insufficient. Study Design We conducted a retrospective cohort study using a nationwide Korean database. The pregnancy group included

Background and Hypothesis Intergenerational factors are implicated in development of schizophrenia spectrum disorders. Studying psychosis spectrum (PS) symptoms dimensionally in a longitudinal, prospective intergenerational cohort can provide crucial insight into risk pathways. Thus, we established the Philadelphia Family Neurodevelopmental Cohort (PFNC), an intergenerational study that follows Philadelphia

Background and Hypothesis Schizophrenia presents significant treatment challenges, particularly due to medication resistance observed in some patients receiving antipsychotics. Emerging research suggests a potential link between impaired reinforcement learning, the severity of psychotic symptoms, and dopamine system abnormalities. Exploring reinforcement learning in therapeutic settings could provide

Background and Hypothesis Large-scale whole exome sequencing (WES) analyses have implicated rare protein-truncating variants (PTVs) in the AKAP11 gene contributing to schizophrenia risk. Previous studies reported alterations of EEG characteristics and synaptic proteome in Akap11 mutant mice. We hypothesize that synaptic dysfunction contributes to AKAP11 deficiency in the pathogenesis of schizophrenia

Background and Hypothesis The multifactorial pathogenesis of schizophrenia (SZ) hinders the diagnosis and treatment of this disorder. Niacin skin flushing response (NSFR) has been identified as an endophenotype for SZ, but the proportion of blunted NSFR (BNR) varied between studies. This study aims to clarify the relationship between NSFR and SZ through a meta-analysis. Study Design PubMed, Embase

Cognitive impairment is a prominent feature of psychosis-spectrum disorders that impedes functional recovery. Globally, clinical guidelines recommend that evidence-based treatments, including cognitive remediation and cognitive compensation, are offered to people with psychosis with cognitive impairment. Clinical guidelines also recommend that, where possible, family is involved in the mental health

Background Shared decision-making (SDM) implementation remains limited in psychosis management, particularly within antipsychotic prescribing. When and why prescribers engage in SDM within these contexts is largely unknown. Part 1 of this two-part realist review aimed to understand the impact of structural and contextual factors on prescriber engagement in SDM within antipsychotic prescribing. Study

Background Shared decision-making (SDM) implementation remains limited in psychosis management, particularly within antipsychotic prescribing. When and why prescribers engage in SDM within these contexts is largely unknown. Part 2 of this 2-part realist review aimed to understand what SDM intervention strategies and local implementation contexts are responsible for successful prescriber engagement

Background and Hypothesis Cognitive impairment, a key feature of psychosis, is linked to poor functional outcomes. This study aimed to identify predictors and outcomes associated with cognitive decline in psychotic disorders. Study Design Data were taken from the Suffolk County Mental Health Project, a first-admission longitudinal cohort study of individuals with psychotic disorders. Participants were

Background and Hypothesis Neurodevelopmental risk-factor models of psychosis highlight the importance of early developmental deviations in the emergence of psychosis. However, few longitudinal studies map neurodevelopment and neurocognitive trajectories across age in preclinical psychosis. We investigated longitudinal trajectories in neurocognition and brain volume in a community cohort of adolescents

Background Foundational models of the psychoses included course as a core element differentiating patients. Current models, ICD-11 and DSM-5, only require symptom criteria to be met to make a diagnosis. We explore the proposition that making course designation essential, again, would improve the categorization of patients with psychotic disorders. Study Design We briefly discuss the history by which

Background Despite the large number of people treated for first-episode psychosis and schizophrenia within the Departments of Defense (DOD) and Veterans Affairs (VA), neither the DOD nor VA had established formal recommendations for the treatment of these conditions. This gap led Congress to require the development of clinical practice guidelines (CPG) for the treatment of schizophrenia. This paper

Background Psychiatric research is increasingly embracing a paradigm shift from categorical diagnoses to neurobiologically meaningful dimensions that cross current diagnostic boundaries. This transposition calls for redefining endophenotypes to accommodate transdiagnostic vulnerabilities. We sought to identify shared and disorder-specific neurocognitive endophenotypes for schizophrenia, bipolar I disorder

Background Cognitive deficits are a central feature of schizophrenia for which there are not any established pharmacological treatments. Antipsychotics are the mainstay of schizophrenia therapy but the effects of these and other psychotropic medications on the cognitive functioning of people schizophrenia have not been extensively studied in routine real-world settings. Study Design A total of 869

Background and Hypothesis Early intervention can improve outcomes for individuals with first-episode psychosis (FEP). We hypothesized that an early detection campaign (ED) targeting the duration of untreated psychosis (DUP) can significantly improve functional outcomes in coordinated specialty care (CSC) patients. Study Design Functional outcomes were compared for FEP patients enrolled from 2014 to

Background Due to the side effects of antipsychotics, overtreatment is an important concern. Previous research focused on antipsychotic polypharmacy and excessively high doses. In this study, the aim is to map changes over the years in potential overtreatment, antipsychotic polypharmacy, total antipsychotic dose, and subjective side effect burden. Moreover, the association of the total dose and antipsychotic

Background and Hypothesis Digital remote monitoring (DRM) captures service users’ health-related data remotely using devices such as smartphones and wearables. Data can be analyzed using advanced statistical methods (eg, machine learning) and shared with clinicians to aid assessment of people with psychosis’ mental health, enabling timely intervention. Such methods show promise in detecting early signs

Background From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early intervention services (EIS), this study aimed to examine latent trajectories of positive and negative

Background and Hypothesis Schizophrenia manifests large heterogeneities in either symptoms or brain abnormalities. However, the neurobiological basis of symptomatic diversity remains poorly understood. We hypothesized that schizophrenia’s diverse symptoms arise from the interplay of structural and functional alterations across multiple brain regions, rather than isolated abnormalities in a single area

Individuals with first-episode psychosis (FEP) are at increased risk for suicide, though few studies have examined the extent to which emotion regulation abnormalities contribute to this risk. The current study sought to address this gap by examining which stages of emotion regulation (ie, identification, selection, implementation) are related to suicidal ideation among individuals with FEP. Forty-one

Background and Hypothesis Both elevated inflammatory markers and aberrant functional connectivity have been detected in patients with schizophrenia, but there is limited knowledge on the relationship between the two phenomena. Some positive symptoms may arise from external misattribution of self-generated actions mediated by decoupling of the default mode network (DMN) with sensory processing regions

Background and Hypothesis Abdominal low-intensity pulsed ultrasound (LIPUS) stimulation has potential as a novel therapeutic strategy against neuroinflammation via inhibition of inflammatory responses in the colon. This study aimed to evaluate whether abdominal LIPUS could alleviate MK-801-induced schizophrenia-like negative symptoms through gut–brain communication. Study Design Rats administered with

Background and Hypothesis Psychotic symptoms are common in adolescents and predictive of psychiatric disorders. Numerous risk factors have been shown to precede psychiatric disorders. However, investigating individual risk factors does not account for the cumulative effect these risk factors may have. Therefore, we combined well-researched environmental risk factors for psychotic disorder in a composite

Background Computerized auditory training (AT) modestly improves symptoms, cognition, and functioning in schizophrenia. We assessed whether d-amphetamine (AMPH) or memantine (MEM) can enhance gains from 30-h of AT. Methods Antipsychotic-medicated individuals with chronic psychosis (n = 68; mean age 47.03y; M:F = 39:29) completed up to 30 AT sessions (2-3/week; n = 50 completed 30 sessions) in 3 groups:

Background and Hypothesis Given the available findings confirming accelerated brain aging in schizophrenia (SZ), we conducted a study aimed at verifying whether quantitative retinal morphological data enable age prediction and whether schizophrenia patients present with a positive retinal age gap (RAG). Study Design Two samples of patients and controls were enrolled: one included 59 SZ patients and

Background This study explored how baseline insight predicts psychiatric hospitalization risk among 186 individuals with first-episode psychosis in coordinated specialty care (CSC). We hypothesized that insight, a potentially modifiable factor, moderates the relationship between CSC enrollment and outcomes, with a high baseline and stable high insight predicting greater reductions in hospitalizations

Background In psychosis spectrum disorders, maladaptive mental imagery is associated with auditory verbal hallucinations (AVHs). This study evaluates the feasibility, acceptability, and effectiveness of the following 4 imagery techniques in targeting mental imagery and AVHs severity: Imagery Rescripting (ImRs), Promoting positive Imagery de novo (Pos-Im), Metacognitive Imagery techniques (Meta-Im)

Background and Hypotheses Negative symptoms of schizophrenia (NSS) carry a substantial burden, and there are no treatments currently approved for NSS. The efficacy of pimavanserin, a selective 5-HT2A inverse agonist and antagonist, in treating NSS was assessed. Study Design ADVANCE-2 was a phase 3, randomized, double-blind, placebo-controlled study of pimavanserin in patients with schizophrenia and

Background and Hypothesis Minor physical abnormalities (MPAs) are neurodevelopmental markers that can be traced to prenatal events and may be significant features of early-onset schizophrenia (EOS). Therefore, our study aimed to (1) find the primary and interaction effects of MPAs for EOS and (2) develop and validate the model for EOS based on explainable machine learning algorithms. Study Design The

Background Young people at clinical high risk for psychosis (CHR-p) commonly experience social impairment, which contributes to functional decline and predicts transition to psychotic illness. Although the use of smart phone technology and social media platforms for social interaction is widespread among today’s youth, it is unclear whether aberrant digital social interactions contribute to risk for

Background Increasing evidence indicates the role of microbiome-gut-brain axis in schizophrenia (SZ). However, few studies have examined the potential links among the gut microbiome, brain structure and function, and clinical manifestation in SZ patients, and the effects of prolonged antipsychotic treatment are often neglected. Study Design A total of 171 participants were enrolled, including 27 drug-naïve

Background and Hypothesis This study aims to develop a placebo response and dropout rate model for acute-phase schizophrenia medication trials and assess factors affecting this response to inform future trial design. Study Design We conducted a literature update using a comprehensive meta-analysis of schizophrenia medication trials, focusing on oral placebo-controlled studies. We modeled the placebo

Background and Hypothesis People with serious mental illness (SMI) have an increased risk of suicide ideation (SI) and suicide behavior (SB). Longitudinal studies on factors contributing to SI/SB in SMI are lacking. Interpersonal biases (ie, perceived burdensomeness and thwarted belongingness) are cross-sectionally related to SI/SB, but do they relate to longitudinal suicide risk or other illness factors

Background The cerebellum has traditionally been associated with motor functions, but recent evidence highlights its critical role in cognitive and emotional regulation, contributing to the neuropathology of schizophrenia. Our previous data-driven research demonstrated that cerebellar-cortical functional connectivity can predict antipsychotic treatment outcomes in first-episode psychosis (FEP). The

Background and Hypothesis Cognitive impairments in patients with schizophrenia initiate a cascade of effects on daily functioning. A single impairment can affect the functioning of the entire cognitive system. However, the relative interdependence among individual neuropsychological measures—whether the performance of a specific test depends on other tests—remains poorly understood. Study Design The

Motor signs are critical features of psychosis that remain underutilized in clinical practice. These signs, including social motor behaviors, mechanistically relevant motor signs, and other motor abnormalities, have demonstrated potential as biomarkers for early detection and intervention. However, their application in clinical settings remains limited due to challenges such as cost, accessibility

Background and Hypothesis Although the psychometric high-risk method based on schizotypy has proven to be a highly cost-effective strategy for unraveling etiological factors for schizophrenia-spectrum disorders, there is a paucity of longitudinal studies with nonclinical populations. This study analyzed the predictive validity of positive and negative schizotypy in a longitudinal project (Barcelona

Background and Hypothesis Mental time travel (MTT) is a crucial ability for daily life. Personal goal-related MTT events has stronger phenomenological characteristics than personal goal-unrelated ones, ie, the “personal goal-advantage effect”. However, it remains unclear whether this effect is impacted in individuals with high schizotypal traits (HST) and the neural correlates of this effect have yet

Background New theoretical and measurement models related to Bayesian networks can usefully be implemented to enrich our understanding of psychosis risk. The present study aims to explore, using a directed acyclic graph (DAG), the putative causal relationship within schizotypal facets, as well as between schizotypal dimensions, psychopathology, and reflective functioning (RF) impairments, in a representative

Background and Hypothesis Disorganized thinking is a prominent feature of schizophrenia that becomes persistent in the presence of treatment resistance. Disruption of the default mode network (DMN), which regulates self-referential thinking, is now a well-established feature of schizophrenia. However, we do not know if DMN disruption affects disorganization and contributes to treatment-resistant schizophrenia

Background and Hypothesis Previous studies on Empathic Accuracy Task (EAT) suggested patients with schizophrenia exhibited altered brain activations in the precuneus, middle frontal gyrus, and thalamus. However, it remains unclear whether individuals with schizotypy would exhibit similar alterations of brain activations associated with EAT. This study aimed to examine the relationships between schizotypy

Background and Hypothesis Evidence suggests that emotion regulation is related to schizotypal traits and negative affect in adults. Few studies examined the interplay among these constructs in school-aged children. We examined the complex relationship between schizotypal traits, emotion regulation, and negative affect in children aged 9–12 years. Study Design One-thousand-and-nineteen children completed

Background and Hypothesis Schizotypy can be utilized as a phenotypic risk marker for schizophrenia and its spectrum and might relate to putative dimensional biological markers of the psychosis spectrum. Among these are amygdala function and structure, which are impaired in schizophrenia, but possibly also correlated with subclinical expression of schizotypy in nonclinical samples. We tested whether

Background and Hypothesis Many patients with psychiatric disorders show increased temporal discounting (TD), ie, they discount future rewards more steeply than healthy controls. However, findings for schizophrenia and schizotypy, a personality constellation considered to be on the schizophrenia spectcrum, are less clear. Moreover, the role of future time representation in TD in the schizophrenia spectrum

Background and Hypothesis Schizotypy is a well-established phenotype for psychosis proneness and risk. Yet, its genetic underpinnings and relations to genetic bases of the schizophrenia spectrum are not well understood owing to conflicting findings. In a deep phenotyping approach, we hypothesized that genetic markers of risk for and to schizophrenia are differentially associated with (trait-level)

Background and Hypothesis Social anhedonia is a core feature of schizotypy and correlates significantly with social functioning and range adaptation. Range adaptation refers to representing a stimulus value based on its relative position in the range of pre-experienced values. This study aimed to examine the resting-state neural correlates of range adaptation and its associations with social anhedonia

Objective Schizotypy as a psychosis proneness marker has facilitated the study of schizophrenia spectrum models, linking phenotypic psychosis risk to brain structural and functional variation. However, association studies to structural connectome markers are limited and often do not consider relations to genetic risk. We tested the hypothesis that dimensions of schizotypy (rather than overall phenotype

Background and Hypothesis Schizotypy is a risk phenotype for the psychosis spectrum and pilot studies suggest a biological continuum underlying this phenotype across health and disease. It is unclear whether this biological continuum might include brain structural associations in networks altered in schizophrenia spectrum disorders, such as the fronto-thalamo-striatal system or nodes of the default

Background Alterations of white matter microstructure have been reported in the psychosis spectrum. However, the development of these alterations during preclinical stages remains poorly understood. The framework proposed by schizotypy research as the personality base for liability to develop psychosis spectrum disorders offers 3 interconnected dimensions thought to impact neurodevelopment, affording

Background and Hypothesis Visual impairments have been proposed as risk factors for psychotic symptoms and illnesses. Visual impairments can considerably impact people’s daily lives, but little is known about the impact and diagnostic sensitivity of such abnormalities for schizotypal personality traits. This study aims to explore possible relationships between schizotypy and visual acuity (VA), contrast

Background and Hypothesis Consistent with diathesis-stress models, psychosis research has focused on genetic moderation of adverse environmental exposures. In contrast, the Differential Susceptibility (DS) model suggests that the same genetic variants that increase risk-inducing effects of adverse experiences also enhance beneficial effects from positive experiences. This study examined whether individuals

Background and Hypothesis In the past decade, significant advances have been made in finding genomic risk loci for schizophrenia (SCZ). This, in turn, has enabled the search for SCZ resilience loci that mitigate the impact of SCZ risk genes. We identified the first genomic resilience profile for SCZ, completely independent from known risk loci for SCZ, though it remains unclear whether resilience loci

Background and Hypothesis Impairments in introspective accuracy (IA) are prominent among schizophrenia patients and detrimentally affect daily functioning, making IA a potential therapeutic target. Recent research highlights the role of the right rostrolateral prefrontal cortex (rlPFC) in IA and suggests that transcranial direct current stimulation (tDCS) to this region may improve it. Therefore, we

Background and Hypothesis Schizophrenia spectrum disorder (SSD) is a chronic neuropsychiatric illness accompanied by significant brain structural and functional abnormalities and higher rate of cardio- and cerebrovascular comorbidities. We hypothesized that genetic and environmental risk factors that led to SSD act throughout the body and demonstrated the association between lower integrity of peripheral

Background and Hypothesis Social cognitive and neurocognitive performance is impacted in autism and schizophrenia spectrum disorders (SSDs). Here, we compared social cognitive and neurocognitive performance across a large transdiagnostic sample of participants with autism, SSDs, and typically developing controls (TDCs). Study Design Participants (total N = 584; autism N = 100, SSDs N = 275, TDCs N