Shared genetic risk has been shown across psychiatric disorders. In particular, anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and schizophrenia (SCZ) show shared genetic risk that matches clinical evidence of shared illness and cognitive phenotypes. Given this evidence, we leveraged a large US-based population-based study to determine genetic associations of disorder-specific and shared psychiatric, cognitive, and brain markers and explore whether the latter might be state versus trait markers in eating disorders.

We used data from the population-based Philadelphia Neurodevelopmental Cohort (N = 4,729) and conducted sex-stratified analyses to test for associations between genetic risk for three disorders (AN, OCD, and SCZ) and mental health phenotypes, neurocognitive traits, and cortical features in a non-clinical population. Exploratory analyses on cortical features were run on a subset with neuroimaging data (N = 626).

Genetic risk for AN was significantly associated with body image distortion (pFDR = 0.02), and body image distortion was significantly related to a reduction in grey matter volume (pFDR = 0.05).

Genetic risk for AN associates with AN trait in a non-clinical sample of youth, particularly in females. Whilst genetic risk was not associated with cognitive or cortical markers, the AN phenotype was associated with cortical markers.

How psychotic symptoms, depressive symptoms, cognitive deficits, and functional impairment may interact with one another in schizophrenia or bipolar disorder is unclear.

This study explored these interactions in a discovery sample of 339 Chinese, of whom 146 had first-episode schizophrenia and 193 had bipolar disorder. Psychotic symptoms were assessed using the Positive and Negative Symptom Scale; depressive symptoms, using the Hamilton Depression Rating Scale; cognitive deficits, using tests of processing speed, executive function, and logical memory; and functional impairment, using clinical assessments. Network models connecting the four types of variables were developed and compared between men and women and between disorders. Potential causal relationships among the variables were explored through directed acyclic graphing. The results in the discovery sample were compared to those obtained for a validation sample of 235 Chinese, of whom 138 had chronic schizophrenia and 97 had bipolar disorder.

In the discovery and validation cohorts, schizophrenia and bipolar disorder showed similar networks of associations, in which the central hubs included ‘disorganized’ symptoms, depressive symptoms, and deficits in processing speed during the digital symbol substitution test. Directed acyclic graphing suggested that disorganized symptoms were upstream drivers of cognitive impairment and functional decline, while core depressive symptoms (e.g. low mood) drove somatic and anxiety symptoms.

Our study advocates for transdiagnostic, network-informed strategies prioritizing the mitigation of disorganization and depressive symptoms to disrupt symptom cascades and improve functional outcomes in schizophrenia and bipolar disorder.

Structural abnormalities in cortical and subcortical brain regions are consistently observed in schizophrenia; however, substantial inter-individual variability complicates identifying clear neurobiological biomarkers. The Person-Based Similarity Index (PBSI) quantifies individual structural variability; however, its applicability across schizophrenia stages remains unclear. This study aimed to compare cortical and subcortical structural variability in recent-onset and chronic schizophrenia and explore associations with clinical measures.

Neuroimaging data from 41 patients with recent-onset schizophrenia, 32 with chronic schizophrenia, and 59 healthy controls were analyzed. The PBSI scores were calculated for cortical thickness, surface area, cortical gray matter volume, and subcortical volumes. Group differences in PBSI scores were assessed using linear regression and analysis of variance. Correlations between the PBSI scores and clinical measures were also examined.

Both patients with recent-onset and chronic schizophrenia exhibited significantly lower PBSI scores than healthy controls, indicating greater morphometric heterogeneity. However, significant differences between the recent-onset and chronic patient groups were limited to subcortical and cortical thickness PBSI scores. Correlations between PBSI scores and clinical symptoms are sparse and primarily restricted to surface area variability and symptom severity in patients with recent-onset schizophrenia.

Patients with schizophrenia show marked structural brain heterogeneity compared with healthy controls, which is detectable even in the early stages of the illness. Although there were few differences in PBSI scores between the recent-onset and chronic schizophrenia groups and limited correlations between PBSI scores and clinical measures, the PBSI may still provide valuable insights into individual differences contributing to clinical heterogeneity in schizophrenia.

Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability.

Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals.

SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences.

SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.

Antipsychotics are first-line treatments for schizophrenia, yet many patients show inadequate response. Clozapine, the gold standard for treatment-resistant schizophrenia, remains underutilised due to safety and monitoring concerns.

To evaluate the adverse effects of clozapine in schizophrenia through a meta-analysis of randomised controlled trials (RCTs).

We systematically searched MEDLINE, CENTRAL, Embase, PsycINFO, ClinicalTrials.gov and WHO ICTRP up to 10 October 2024 for RCTs comparing clozapine (as either monotherapy or combination therapy) with other antipsychotics. We assessed 37 distinct adverse outcomes. Risk ratios were calculated for dichotomous outcomes and standardised mean differences for continuous outcomes, with confidence intervals.

A total of 116 RCTs (n = 8431) were included. In 69 monotherapy RCTs (n = 6281), clozapine showed no difference in either mortality (risk ratio 1.01, 95% CI: 0.50, 2.01, prevalence 0.1%) or discontinuation due to adverse effects (risk ratio 1.18, 95% CI: 0.91, 1.53, prevalence 7.2%). Agranulocytosis risk was nearly tripled (risk ratio 2.81, 95% CI: 0.97, 8.12, prevalence 0.7%), although with wide confidence intervals. Clozapine increased the risk of seizures (risk ratio 3.61, 95% CI: 1.80, 7.95, prevalence 3.1%) and orthostatic hypotension/bradycardia/syncope (risk ratio 1.66, 95% CI: 1.00, 2.77, prevalence 11%). No difference was found for myocarditis/cardiomyopathy (risk ratio 0.33, 95% CI: 0.01, 8.13). Clozapine increased the risk of leukopenia, hypersalivation, sedation, tachycardia, hypertension, constipation, nausea/vomiting, fever, flu-like syndrome and headache. In 47 combination RCTs (n = 2150), clozapine combinations were not associated with increased risk of severe adverse effects; no cases of agranulocytosis (21 RCTs, n = 894) or seizures (8 RCTs, n = 313) were reported in trials that explicitly assessed these outcomes.

Life-threatening adverse events remain rare with clozapine. With appropriate monitoring, its safety profile supports broader and potentially earlier use. Future studies should refine monitoring protocols and explore additional indications.

A better mechanistic understanding of schizophrenia spectrum disorders is crucial to developing efficient treatment approaches. Therefore, this study investigated longitudinal interrelations between clinical outcomes, brain structure, and somatic health in post-acute individuals from the schizophrenia spectrum.

A sample of 63 post-acute patients from two independent physical exercise studies was included in the final analyses. Demographic, clinical, cognitive, and somatic data were acquired at baseline and follow-up, as were structural magnetic resonance imaging scans. Multivariate cross-lagged panel modeling including mediators was used to study the mutual interrelations over time between the clinical, neural, and somatic levels.

A higher baseline global gray matter volume and larger regional gray matter volumes of the hippocampal formation, precuneus, and posterior cingulate predicted improved clinical outcomes, such as daily-life functioning, negative symptoms, and cognition. Increases in white matter volume from baseline to follow-up resulted in significantly reduced positive symptoms and higher daily-life functioning.

Our findings suggest that stimulating neuroplasticity, especially in the hippocampal formation, precuneus, and posterior cingulate gyrus, may represent a promising treatment target in post-acute schizophrenia spectrum disorders. Physical exercise therapies and other lifestyle interventions, and brain stimulation approaches reflect potential treatment candidates. Given the exploratory character of the statistical analysis performed, these findings need to be replicated in independent longitudinal imaging cohorts of patients with schizophrenia spectrum disorders.

Schizophrenia is a severe psychiatric disorder characterised by positive symptoms, such as hallucinations and delusions, which are linked to dysregulated striatal connectivity. Although traditional models highlight the limbic striatum’s role in salience processing, emerging evidence suggests that the associative striatum, critical for cognitive control and habit formation, also plays a significant role. However, the structural connectivity underlying striatal subregions and its relationship to symptom severity and treatment response remains poorly understood.

This study aimed to investigate the structural connectivity of striatal subregions in first-episode schizophrenia (FE-SCZ) patients and to evaluate its association with positive symptoms and changes following antipsychotic treatment.

We recruited 80 FE-SCZ patients and 80 healthy controls who underwent diffusion tensor imaging probabilistic tractography to assess white matter tract strength between the striatum and ten cortical targets. Longitudinal analysis was conducted in patients at baseline (within 2 weeks of initial antipsychotic exposure) and after ongoing treatment to evaluate changes in connectivity and their relationship to symptom improvement.

FE-SCZ patients exhibited reduced connectivity between the dorsolateral prefrontal cortex (dlPFC) and associative striatum and increased connectivity between the anterior cingulate cortex (ACC) and associative striatum compared to controls. Longitudinal analysis revealed that antipsychotic treatment increased dlPFC–associative striatum connectivity and decreased ACC–associative striatum connectivity, which correlated with reductions in positive symptom severity.

These findings highlight the critical role of striatal subregions in the pathophysiology of schizophrenia, emphasising the associative striatum’s involvement in cognitive control and salience attribution. Changes in striatal connectivity after continued antipsychotic therapy may serve as a biomarker for symptom improvement, advancing our understanding of schizophrenia and guiding future therapeutic strategies.

The treatment response for the negative symptoms of schizophrenia is not ideal, and the efficacy of antidepressant treatment remains a matter of considerable controversy. This systematic review and meta-analysis aimed to assess the efficacy of adjunctive antidepressant treatment for negative symptoms of schizophrenia under strict inclusion criteria.

A systematic literature search (PubMed/Web of Science) was conducted to identify randomized, double-blind, effect-focused trials comparing adjuvant antidepressants with placebo for the treatment of negative symptoms of schizophrenia from database establishment to April 16, 2025. Negative symptoms were examined as the primary outcome. Data were extracted from published research reports, and the overall effect size was calculated using standardized mean differences (SMD).

A total of 15 articles, involving 655 patients, were included in this review. Mirtazapine (N = 2, n = 48, SMD −1.73, CI −2.60, −0.87) and duloxetine (N = 1, n = 64, SMD −1.19, CI −2.17, −0.21) showed significantly better efficacy for negative symptoms compared to placebo. In direct comparisons between antidepressants, mirtazapine showed significant differences compared to reboxetine, escitalopram, and bupropion, but there were no significant differences between other antidepressants or between antidepressants and placebo. No publication bias for the prevalence of this condition was observed.

These findings suggest that adjunctive use of mirtazapine and duloxetine can effectively improve the negative symptoms of schizophrenia in patients who are stably receiving antipsychotic treatment. Therefore, incorporating antidepressants into future treatment plans for negative symptoms of schizophrenia is a promising strategy that warrants further exploration.

Significant changes in Taiwan’s psychiatric services over recent decades include expansion of community-based clinics and implementation of the Schizophrenia Pay-for-Performance programme.

This study aimed to assess the trend of the quality of healthcare for individuals with schizophrenia, using various indicators of the treatment process and outcomes between 2010 and 2019.

Individuals with schizophrenia were identified using Taiwan’s National Health Insurance claims database. The quality of healthcare for individuals with schizophrenia was assessed using treatment process and outcome indicators, including antipsychotic types, medication adherence, daily dose for antipsychotics and concurrent use of other psychotropic agents. Outcome indicators included all-cause mortality, suicide deaths, psychiatric hospitalisation, emergency department visits and employment status.

Antipsychotic medication usage has shifted towards second-generation antipsychotics (SGAs) and long-acting injectable antipsychotics (LAIs), with declines in first-generation antipsychotics. The percentage of medication adherence declined, while that of individuals with an adequate daily dose increased. Concurrently, anticholinergic and benzodiazepine use decreased while antidepressant and mood stabiliser use increased. Outcome indicators showed no significant change in all-cause mortality or suicide rates over time, but there were reductions in psychiatric hospitalisations and emergency department visits. Employment rates increased overall, particularly in urban areas.

The quality of healthcare for individuals with schizophrenia, as measured by treatment process and outcome indicators, improved alongside changes in Taiwan’s psychiatric services; however, causality cannot be inferred from our findings. Future research should evaluate the effectiveness of psychiatric service policies and continuously monitor healthcare quality to further enhance the lives of individuals with schizophrenia.

Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.

A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.

Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.

Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.