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...

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...

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...

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...

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...

In-scanner head motion is a recognized source of bias in structural magnetic resonance imaging (sMRI), yet it remains under-addressed in psychiatric neuroimaging where structural difference in patient populations are considered foundational. We examined motion-related bias in grey matter volume estimates across eight independent cohorts comprising 9,664 individuals, including 8,979 neurotypical controls (NC), 497 patients with schizophrenia (SCZ), and 188 patients with bipolar disorder (BD). Mot...

BackgroundEarly detection of individuals at risk for clinical deterioration in first-episode psychosis (FEP) remains a vital challenge in psychiatric care. Emerging evidence indicates that immune dysregulation might play a crucial role in the pathophysiology and progression of psychotic disorders. AimsThis study examined the predictive potential of a plasma cytokine and chemokine panel in anticipating clinical stage transition of FEP patients. MethodUsing multiplex immunoassays, plasma samples...

Background and HypothesisClozapine is the only antipsychotic with protective effects against suicide in schizophrenia (SCZ). Newer third-generation antipsychotics (TGA) have better tolerability and modulate serotonin, dopamine, and N-methyl-d-aspartate neurotransmission pathways implicated in suicide. We aimed to investigate the effects of TGAs on suicide in SCZ. MethodsWe searched seven databases up to December 2023 for SCZ studies that reported suicide data. The primary outcome was suicide de...

ObjectiveCognitive deficits are a leading cause of disability in schizophrenia and are linked to poor functional outcomes. There are no first line treatments for these deficits, and their neural basis is poorly understood. While schizophrenia is associated with widespread cognitive deficits, information processing speed is most profoundly impaired. Processing speed deficits have been associated with hyperconnectivity in the Default Mode Network (DMN). We therefore tested if modulating DMN connec...

BackgroundLipidomic alterations have been reported across schizophrenia (SCZ) and bipolar disorder (BD), but findings are heterogeneous and often overlap across diagnoses, limiting diagnostic specificity. Associations between lipid profiles and illness severity have also been inconsistent when assessed using single symptom scales, raising the possibility that unidimensional measures fail to capture biologically relevant variation. Whether plasma lipidomic alterations relate to multidimensional p...

Psychotic disorders are increasingly recognized as the extreme end of a progressive psychopathology continuum, with less advanced stages including the asymptomatic familial high-risk state (FHR), the help-seeking clinical high-risk state (CHR), and first episode psychosis (FEP). However, we lack a comprehensive study of clinical, cognitive, functional, and neuroanatomical markers across all three early stages of psychosis, limiting our understanding of how the multimodal phenotypes which define ...

ObjectiveWe examined the clinical utility of resting state electroencephalography (rsEEG) by evaluating its temporal stability, discriminant validity for B-SNIP psychosis Biotypes, and suitability as a treatment target for brain stimulation. MethodsWe collected 5 minutes of eyes-open rsEEG from 1401 participants with psychosis and 750 healthy persons. A subset of participants was re-tested after 6 months and 12 months (N=109). In a pilot target engagement study (n=5) we collected rsEEG before a...

Schizophrenia is a severe neuropsychiatric disorder characterized by positive and negative symptoms and cognitive impairments. The present study aimed to investigate the potential interference of ambient noise on the performance of executive function (EF) tasks in individuals with schizophrenia. The sample consisted of 40 participants, divided equally into two groups: a group of individuals with schizophrenia (SchG) and a healthy control group without neuropsychiatric disorders (HC). All partici...

Background and HypothesisSchizophrenia is a disease characterized by various symptoms and has severe lifelong impacts on patients and their families. Despite various hypotheses and associated studies, the key mechanism in schizophrenia is not fully elucidated. In the present study, we focused on adropin, a peptide regulating energy metabolism, antioxidation, and neuroprotection. Study DesignIn both the group of healthy volunteers (HV) and the group of patients with some schizophrenia spectrum a...

Psychiatric disorders are fundamentally challenged by symptom heterogeneity, high comorbidity, and the absence of objective biomarkers, which together result in substantial variability in clinical assessment and treatment selection. Patient-generated language captures rich information about subjective experience and symptom severity, which can be systematically encoded and analyzed using computational models, making it a scalable signal for psychiatric assessment. We compare two approaches: (i) ...

Background At present, there are no approved pharmacological treatments for people at clinical high risk for psychosis (CHR-P). We sought to assess the acceptability of cannabidiol (CBD): a promising candidate treatment for this population. Methods CHR-P individuals completed a survey which assessed their views on the acceptability of CBD, its expected effectiveness and side effects, and on formulation preferences. Results The sample comprised 55 CHR-P individuals (24.3 years and 69% female). Mo...

BackgroundWhile growing evidence implicates sleep-wake and circadian rhythm disturbances (SCRDs) in the onset and course of mood and psychotic disorders, longitudinal studies using objective measures are limited. This clinical cohort study examined whether actigraphy-derived SCRDs (sleep duration, timing, and efficiency) predicted transition to (i) any full-threshold mental disorders; and then specifically: (ii) full-threshold bipolar or psychotic disorders or (iii) other full-threshold (i.e. de...

Schizophrenia is a serious mental disorder characterized by enhanced sensory-perceptual alterations. We investigated face identity recognition in people with schizophrenia with the Facial Identity Recognition Structured Task (FIRST) develop at our laboratory. This was created with natural interference features (beard, makeup and mask). This task consists in six block-trails of six images for identity recognition. Forty three adult volunteers divided into two groups: a Health Control (HC) and a g...

Background and HypothesisAbnormal default mode network (DMN) connectivity was observed in both tobacco use and psychotic spectrum disorders, but it remains unknown how psychosis impacts the relationship between connectivity and tobacco use. Interventions targeting the left lateral parietal DMN node (LLPDMN) have modulated DMN connectivity and nicotine craving in psychosis. We aimed to investigate relationships between DMN connectivity, psychotic illness, and tobacco use. Study Design336 partici...