Schizophrenia Bulletin

BackgroundEEG microstates provide a window into rapid, large-scale brain network dynamics. Despite showing alterations in schizophrenia, evidence in first-episode schizophrenia spectrum psychosis (FESSP) is limited. We assessed whether microstate temporal and transition features could identify a multivariate signature of FESSP, and whether these dynamics can track symptom severity. MethodsResting-state EEG was analysed in 69 participants (FESSP n=41, mean age: 22.49 years; healthy controls n=28...

In schizophrenia spectrum disorders (SSD), structural alterations of the gray matter (GM) and white matter (WM) have been widely described. However, the complex interplay between early disease-related changes and ongoing brain maturation challenges our ability to identify early biomarkers. In this study, we investigated structural abnormalities and their association with symptoms in a drug-naive or minimally medicated sample comprising 113 patients with SSD and 112 neurotypical controls. Specifi...

Backgroundspeech carries cues to variation in mental state in schizophrenia spectrum disorders/psychotic disorders, typically indexed with clinician-rated scales such as the PANSS. Progress in the automation of speech-based symptom modelling has been constrained by data scale and the underrepresentation of low-resource languages. In this study, we aggregate multi-center recordings to assemble a large corpus and assess symptom-prediction models at scale, to enable more objective and efficient ass...

BackgroundSchizophrenia often features low-grade neuroinflammation. Because latent toxoplasmosis (LT) is common in this population, we tested whether LT yields a biomarker pattern resembling that reported in schizophrenia. MethodsWe quantified 15 cytokines and 15 blood markers of brain injury in 65 LT-positive individuals and 103 matched LT-negative controls using multiplex immunoassays. Multivariate effects of infection, age, sex, and their interaction were assessed by MANCOVA and PERMANOVA. E...

Cognitive heterogeneity is a core feature of schizophrenia (SCZ). Conventional approaches examine this heterogeneity using domain-specific scores, which may not fully reflect the underlying cognitive structure. In this study, a norm-anchored cognitive structural deviation (NCSD) framework was developed to examine such heterogeneity from a structure-informed perspective. The HC-derived latent cognitive structure (N-LCS) captured performance across the assessed tasks and remained stable under exte...

Schizophrenia spectrum disorders (SSD) are characterized by altered brain structure, reflecting widespread dysconnectivity across brain-specific networks. However, the role of hierarchical organization on cortical morphometric networks in shaping clinical outcomes over the course of the disease remains unclear. Connectome-derived gradients have increasingly been used to investigate spatial transitions in brain organization. Here, we computed cortical and subcortical Morphometric INverse Divergen...

When the brain and body misalign, emotional experience and sense of reality can be disrupted. Although such atypical experiences are central to schizophrenia spectrum disorders (SSD), interoception, processing of internal bodily signals, remains poorly understood in individuals with SSD, particularly across subjective, behavioural, and neural domains. We tested whether SSD is associated with convergent alterations across interoceptive domains and whether these relate to clinical symptoms in a cr...

Combining multi-site MRI datasets increases statistical power and model generalisability but may be hindered by variability between sites. Harmonisation methods aim to remove potentially confounding variance while preserving biologically meaningful signals. However, this can be challenging, as each T1-weighted image reflects both scanner properties (e.g., field strength, sequence parameters) and individual biological characteristics (e.g., age, sex, ethno-cultural background, and pathology). Two...

Understanding factors that predict the course of schizophrenia remains essential for improving long-term clinical management. Rate and severity of symptom exacerbations vary widely across individuals, and although prior studies have examined potential predictors, findings have been inconsistent and often limited by small samples, infrequent assessments, and non-standardized measures. Using data from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), which include...

BackgroundAntipsychotic medications are recommended for managing schizophrenia spectrum disorders, yet their long-term effects on functional recovery remain unclear. Existing evidence is conflicting, often derived from between-subject comparisons vulnerable to confounding by indication. MethodsWe conducted a nationwide register-based cohort study of 65,630 individuals with incident schizophrenia spectrum disorders in Denmark (1998-2023). We modelled antipsychotic exposure against productive en...

BackgroundPrediction of response to antipsychotic medications remains elusive, and a biomarker assisting in treatment selection would drastically improve prognosis. The 40 Hz auditory steady state response (ASSR) is an EEG biomarker, mirroring the GABA-glutamate signaling and the excitation/inhibition balance, consistently been reported to be impaired in schizophrenia, on, with inconsistent evidence of an association with specific symptoms. MethodsN=69 schizophrenia inpatients with an acute psy...

BackgroundAntipsychotics are central to relapse prevention in schizophrenia, but longer-term use is associated with adverse effects that often prompt dose reduction or discontinuation. Although relapse risk increases after discontinuation, the nature of relapse remains unclear. Specifically, it is uncertain whether relapse reflects re-emergence of underlying illness or pharmacological withdrawal. MethodsWe analysed longitudinal symptom data (Positive and Negative Syndrome Scale; PANSS) from 417...

Working memory (WM) impairments have been reported in different stages of psychosis but whether their neural correlates are shared or stage-specific is unknown. This meta-analysis examined WM-related brain activity across psychosis stages: familial and clinical high-risk for psychosis (at-risk stage), first-episode psychosis (early psychosis stage), and chronic schizophrenia (chronic psychosis stage). PubMed, Ovid, and Web of Science were searched up to July 2025 for functional magnetic resonanc...

Task-based functional magnetic resonance imaging (fMRI) examines how the brain dynamically responds to cognitive and perceptual demands, offering complementary insight beyond traditional activation-based analyses in schizophrenia. Prior task-based fMRI studies have identified reduced functional connectivity within auditory and associated cortical areas. In this study, we investigated task-evoked functional connectivity and brain state dynamics in 25 healthy controls, 23 patients with schizophren...

BackgroundAuditory hallucinations are among the most disabling symptoms in individuals with schizophrenia (SZ) and are linked to aberrant signaling within deep-striatal circuits, such as the nucleus accumbens (NAc) and caudate head (CH). However, causal tests of striatal involvement have been limited by the inaccessibility of these structures using noninvasive neuromodulatory techniques. Low-intensity focused ultrasound (LIFU) provides millimeter-scale precision capable of modulating deep-brain ...

Schizophrenia spectrum disorders (SSDs) are clinically and biologically heterogeneous and lack reliable biomarkers for stratification and outcome prediction. Evidence from postmortem, fluid biomarker, and neuroimaging studies suggests that blood-brain barrier (BBB) dysfunction may contribute to pathophysiology in a biologically defined subgroup. However, findings are inconsistent and often based on cross-sectional or indirect measures. The IMPACT study is a longitudinal, multimodal investigatio...

BackgroundEmerging evidence suggests that cognitive impairment cuts across traditional psychiatric diagnoses and may reflect a shared underlying cognitive liability. We examined whether a general cognitive factor (gFc) accounts for transdiagnostic deficits across schizophrenia (SZ), bipolar disorder (BD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD). MethodsA total of 472 affected individuals and 253 population healthy controls (HC) completed a standardized cognitive bat...

BackgroundCerebellar transcranial magnetic stimulation (TMS) may serve as an adjuvant therapy for psychosis symptoms, most recently we have shown improvements in negative symptoms. Historically, cerebellum TMS has not utilized functional neuroanatomy for targeting, and the precision of TMS to the cerebellum is unclear. A classical view of the cerebellum as solely involved in motor computations has been updated with the discovery of rich non-motor connectivity including the default, dorsal attent...

ImportanceLarge language models (LLMs) have demonstrated diagnostic potential in several medical specialties, but their application to psychiatry - where diagnosis relies heavily on clinical judgment, narrative interpretation, and reasoning under uncertainty - remains insufficiently evaluated. ObjectiveTo evaluate diagnostic accuracy and clinician-judged reasoning quality of multiple large language models using psychiatric case vignettes. DesignMixed-methods evaluation study of diagnostic accu...

Auditory-verbal hallucinations (AVHs) are among the most disabling symptoms of schizophrenia and often persist despite the use of adequate antipsychotic treatment. Conventional low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the T3P3 scalp site has demonstrated limited efficacy, likely due to interindividual variability in AVH-related brain networks. In this multicenter, randomized, double-blind phase 3 trial, 70 patients with drug-resistant AVHs received active 1-Hz ...