Paranoid ideation relates to a mistrust or suspicion of other people and their motives and may be especially influenced by environmental and psychosocial factors. Historically marginalized populations consistently endorse higher levels of paranoid ideation than Non-Hispanic White individuals, but it is unclear whether these differences can be attributed to measurement bias or if they represent genuine between-group differences in the latent construct. The current study aimed to examine the measurement invariance of five common paranoia measures. Participants included Non-Hispanic White (n = 308), Black American (n = 299), and Hispanic (n = 281) groups recruited from the general population. Scales included the Revised-Green Paranoid Thoughts Scale (R-GPTS), Paranoia Scale (PS), Persecution and Deservedness Scale (PaDS), Paranoia/Suspiciousness Questionnaire (PSQ), and the Personality Inventory for the DSM-5 (PID-5) Suspiciousness facet scale. Measurement invariance analyses indicated the R-GPTS, PS, PaDS, PID-5 Suspiciousness facet, and PSQ Negative Mood/Withdrawal and Perceived Hardship/Resentment subscales showed configural, metric, and scalar invariance, while the Interpersonal Suspiciousness/Hostility and Mistrust/Wariness subscales lacked scalar invariance. Black American participants had higher mean scores on all invariant measures, followed by Hispanic and Non-Hispanic White participants. For the scales that displayed scalar invariance, these results are unlikely to be attributable to measurement bias, and instead likely reflect cultural and potentially adaptive responses to the complex relationships between cultural, social, and economic factors. To better understand how demographic variables and social determinants of health may influence paranoid ideation in diverse populations, future research should incorporate these variables into measurement invariance and group difference analyses.

Schizophrenia (SCZ) is a heterogeneous mental disorder with a complex and multifaceted pathophysiology. Current antipsychotic medications based on the hyperdopaminergic hypothesis, fail to achieve adequate symptom improvement in approximately 30 % of patients, indicating the need for novel treatment strategies grounded on homogenous pathophysiology defined by specific biomarkers. Accumulating evidence indicates the presence of zinc (Zn) deficiency in a subpopulation of individuals with SCZ, although its role in SCZ pathophysiology remains underexplored. In this study, we aimed to characterize the clinical features associated with hypozincemia in SCZ to identify a homogeneous subgroup that may benefit from tailored-made treatment with Zn supplementation. A cohort of 497 individuals with SCZ or schizoaffective disorder was classified into hypozincemia (<80.0 μg/dL) and non-hypozincemia groups. Between-group differences in clinical features were examined, and regression analysis was performed to determine the association between serum Zn levels and positive and negative syndrome scale (PANSS) scores. Hypozincemia was diagnosed in 68.0 % of the study participants. The hypozincemia group was characterized by older age, longer disease duration, more frequent hospitalizations, and higher PANSS scores compared with the non-hypozincemia group. After adjusting for age, hospitalization, and antipsychotic medication use, regression analysis demonstrated a significant negative correlation between serum Zn levels and the positive symptom subscale, general psychopathology subscale, and total score. These findings may enhance the understanding of the mechanisms underlying the clinical severity of SCZ and support the potential use of Zn supplementation to mitigate neuropsychiatric symptoms in patients with hypozincemia.

Schizophrenia imposes a global health burden characterized by treatment-refractory cognitive deficits, with converging evidence implicating cerebellar-cortical circuit dysfunction as a pivotal pathophysiological mechanism. In this review, we focus on the advances from neuroimaging, molecular, and therapeutic studies to elucidate the cerebellum's role in schizophrenia-related cognitive pathology. Particularly, we aim to address the advances across four domains: cognitive subtyping in schizophrenia; cerebellar-cortical connectivity evidenced from anatomical, lesion, and neuroimaging studies; multiscale neuropathology in molecular, cellular, and structural alterations; and emerging therapeutics targeting cerebellar nodes through pharmacological, neuromodulatory, and molecular approaches. Collectively, this work supports the cerebellum's role as a critical hub involved in cognitive pathology of schizophrenia.

Although numerous studies have examined the impact of schizophrenia on quality of life (QoL), the results have been mixed. This meta-analysis compared QoL across various domains between schizophrenia patients and healthy controls and identified the moderators of group differences.

This study evaluated the effectiveness of an enhanced WELLFOCUS Positive Psychotherapy intervention (EWPPT) on the well-being, recovery, and quality of life of people with schizophrenia (PWS) in halfway houses in Hong Kong.

Language disorganization is a hallmark of psychosis which has traditionally been assessed through clinical interviews and standardized scales. Recent advances in Natural Language Processing (NLP) and graph theory provide innovative, objective methodologies to analyze language production in psychosis. In particular, dream reports, as a unique form of narrative, offer a valuable lens through which to examine the presence of disorganized linguistic features. This study analyzed structural speech graphs of written and oral dream reports from 193 Italian participants (115 individuals with acute psychosis and 78 healthy controls), focusing on key connectivity attributes, such as the Largest Connected Component (LCC), the Largest Strongly Connected Component (LSC) and their z-scores relative to random graph distributions. Patients with psychosis exhibited significantly lower connectivity values than controls (p < 0.0125), with their speech graphs resembling random word sequences more frequently. These results remained significant after controlling for education (p < 0.05), with LCC and LSCz surviving Bonferroni correction (p < 0.0125). A Naïve Bayes classifier using these features achieved 68 % accuracy (AUC = 0.75), demonstrating the potential for automated classification of psychosis. To our knowledge, this is the first study conducted with native Italian speakers, reinforcing the cross-linguistic validity of graph-based approaches. Also, our findings support the utility of graph analysis in detecting psychosis and reinforce the notion that speech abnormalities can be captured from a topological perspective through reductions in speech connectedness, thereby providing a novel framework for understanding thought and language impairments associated with the disorder.

Psychotic-Like Experiences (PLEs) during early adolescence may precede development of later psychotic disorders. Given evidence of environmental challenges contributing to the psychotic disorder psychopathology, this study examined if child temperament mediates the association between the family environment and PLEs.

First-episode psychosis (FEP) represents a critical period characterized by severe psychotic symptoms, where early intervention is vital. Identifying objective biomarkers to assess symptoms and guide treatment remains a significant challenge. Extracellular vesicles (EVs), particularly their microRNAs (miRNAs), emerge as promising candidates due to their ability to cross the blood-brain barrier and modulate gene expression. Since antipsychotic medications can influence miRNA expression, studying antipsychotic-naïve FEP patients is crucial for isolating disease-specific changes. This study analyzed miRNA expression in serum EVs from 12 antipsychotic-naïve FEP patients, before and after two months of risperidone treatment, comparing results to 12 healthy controls. Next-generation sequencing (NGS) identified 613 miRNAs in total; after filtering out low-expressed transcripts, 428 miRNAs were retained for differential expression analysis. Two miRNAs-miR-335-5p and miR-30d-5p presented reduced expression in FEP patients compared to controls. This reduction persisted after treatment but showed signs of attenuation. Notably, miR-30d-5p expression was negatively correlated with depressive symptoms assessed via the Calgary Depression Scale for Schizophrenia. Additionally, miR-744-5p was upregulated following risperidone treatment, suggesting a potential modulatory effect of the drug on EV miRNA expression. Both miR-30d-5p and miR-744-5p have been previously implicated in mental disorders, neurodevelopment, and schizophrenia-related pathways, with confirmed expression in neurons. Here we also observed that predicted targets from these miRNAs are involved in synaptic related pathways. Although limited by the small sample size, our findings propose novel avenues for psychosis research and biomarker discovery.

Subfield-specific microstructural alterations of the hippocampus and their clinical relevance remain poorly characterized. This study investigated hippocampal subfield-specific microstructural alterations in schizophrenia (SCZ) patients using high-resolution diffusion tensor imaging (DTI).

Disorganized speech can disrupt effective communication in schizophrenia-spectrum disorders (SSDs). Recent work has tied disorganized speech to deficits in metacognitive capacity, or one's capacity to integrate experiences to form complex mental representations. Specifically, recent work has shown that metacognitive deficits may emerge only at higher levels of disorganized speech, suggesting a possible exponential relationship. The present study investigated this relationship in a large sample of 485 adult outpatients with SSDs. We aimed to: 1) broadly characterize the nature of the relationship between metacognitive capacity and disorganized speech; and 2) compare metacognitive capacity across levels of conceptual disorganization. We employed ANOVAs, Tukey's HSD post hoc tests, and curve estimation analyses to answer these questions. Results provide mixed evidence that the relationship between metacognitive capacity and conceptual disorganization is exponential. Critically, we found that as levels of conceptual disorganization increase, there are small, clinically relevant decreases in metacognitive capacity, especially in metacognitive mastery. These findings have clinical implications for tailoring metacognitive interventions for patients with high levels of disorganized speech. Our results highlight the need for including participants with extreme disorganized speech and using multidimensional measures of disorganized speech in future studies.

Schizophrenia is a complex neurodevelopmental disorder characterized by widespread cognitive and behavioral impairments, with the hippocampus playing a critical role in its pathophysiology. While traditional approaches such as animal models and postmortem studies have provided valuable insights, they fall short in capturing the human-specific and developmental features of the disease. Human pluripotent stem cell (hPSC) models, particularly 3D brain organoids, represent a powerful new tool for investigating the cellular and circuit-level mechanisms underlying schizophrenia. Although cortical and striatal organoids have been increasingly utilized in psychiatric research, hippocampal organoid models remain underdeveloped and underused. This review outlines the developmental basis of hippocampal dysfunction in schizophrenia and discusses the emergence of hPSC-derived hippocampal organoids and assembloids as novel in vitro systems. We highlight key findings from the limited studies using hippocampal differentiations in schizophrenia, explore their potential to model region-specific circuitry (e.g., DG-CA3, cortico-hippocampal, and hippocampalstriatal networks), and identify major technical challenges such as the absence of CA1/CA2 subfields, limited vascularization, and the need for microglial integration. Finally, we propose future directions to refine these models and leverage them for mechanistic discovery and therapeutic screening. By integrating genetic, imaging, and developmental perspectives, this review positions hippocampal organoid technology as a promising yet underutilized platform for advancing our understanding of schizophrenia's neurodevelopmental origins.

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder that typically emerges in late adolescence or early adulthood. In rats, administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on gestational day (GD) 17 induces several features resembling those observed in SCZ patients. Preclinical and clinical studies suggest that cannabidiol (CBD) has antipsychotic-like effects. Here, we evaluated whether acute CBD treatment attenuates behavioral deficits and the enhanced dopamine (DA) system activity in the ventral tegmental area (VTA) of adult male and female MAM rats. Pregnant rats received saline or MAM (20 mg/kg) on GD17. In adulthood, offspring were tested in the elevated plus-maze (EPM), novel object recognition (NOR) test, and locomotor responses to the NMDA receptor antagonist MK-801. The in vivo electrophysiological activity of VTA DA neurons was also recorded. CBD (60 mg/kg) was administered 1 h before each behavioral test and electrophysiological recording. Male and female MAM rats exhibited anxiety-like behavior in the EPM, which was not reversed by CBD. In the NOR test, CBD reversed memory impairment in male MAM rats, whereas female MAM rats showed no deficits. Neither male nor female MAM rats exhibited increased locomotor responses to MK-801, and CBD did not affect this behavior. Both male and female MAM rats showed increased VTA DA neuron population activity, which was reversed by CBD in both sexes. Our findings indicate that CBD attenuates cognitive deficits and enhanced DA system activity in the MAM model, supporting the hypothesis that CBD produces antipsychotic-like effects.

Caregiver involvement is critical to outcomes for young people with early psychosis. Caregiver-focused interventions reduce caregiver distress, improve family communication, and increase likelihood of recovery, but many caregivers face barriers to access. Because mHealth interventions can be accessed remotely and require minimal staffing, they could address some of these challenges. Our team conducted a pilot trial of Bolster, an mHealth intervention for early psychosis caregivers, with sixty (N = 60) caregivers to young adults with early psychosis to determine the acceptability and preliminary efficacy of Bolster as well as the feasibility of this approach. Participants were randomized to receive (1) a list of extant online resources (control arm), or (2) these resources alongside the Bolster mobile app (intervention arm). Caregivers used Bolster frequently (30.2 % of days during the intervention period and 10.4 min per use day) and reported finding it usable and helpful in supporting their caregiving activities. Outcome analyses demonstrated improvements in multiple outcomes, including family communication (Cohen's d = 0.86) and caregiver psychological morbidity (d = 0.98). Improvements in the Bolster arm were larger than control for caregiver psychological morbidity (d = 0.61) and distress related to the loved one's illness (d = 0.72), and caregivers in the Bolster arm were more likely to report that their loved one accessed psychotherapy or counseling (aRR = 2.53 [95 % CI: 1.07 to 6.01]) and met with a medication provider (aRR = 2.91 [95 % CI: 1.10 to 7.65]). Results suggest that Bolster is acceptable to caregivers and has promising preliminary efficacy.

Insight, awareness of illness, is often impaired in psychotic disorders and relates to symptom severity and cognition, but its association with time since first diagnosis is unclear. We examined insight, cognition, and time since first diagnosis in a large multi-diagnostic sample.

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The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for assessing symptom severity in schizophrenia. Significant concerns remain regarding its structural validity, with no consensus on a definitive model. Although the five-factor model (positive, negative, cognitive, hostility, and affective) is the most widely accepted, studies have demonstrated instability in item distribution across factors and difficulty in achieving adequate fit indices. This exploratory study aims to evaluate the structural validity of the PANSS, addressing these previously identified issues and contributing to the theoretical debate on the limited evidence supporting a robust model fit.

The role of peripheral glutamate as an accessible biomarker for schizophrenia remains unclear. Its potential to reflect illness progression or differentiate treatment-resistant (TRS) from non-resistant (non-TRS) patients, and its relationship with central glutamate, require further investigation. This exploratory study assessed plasma glutamate levels and their associations with anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) glutamate in both TRS and non-TRS patients. Additionally, we examined associations between plasma glutamate and clinical characteristics, including psychiatric and cognitive measures.

Most of the brain-based biomarker research in schizophrenia (SZ) results from chronic medicated samples. Disambiguating contributions of "primary" disease vs. psychotropic medication effects to the neurobiology of SZ remains challenging. In this study, using 3Tesla pseudo-continuous Arterial Spin Labeling (pCASL), we examined regional cerebral blood flow (CBF) in hippocampus and its cortical projection network in SZ probands [n = 41, including antipsychotic-free (SZ-OFF, n = 14) and treated with antipsychotic(s) (SZ-ON, n = 27)], their first-degree relatives [n = 28, including relatives with lifetime psychosis-spectrum disorders (REL-P, n = 14) and without (REL-NP, n = 14)], and healthy controls (HC, n = 16) [n = 85 total]. SZ-OFF demonstrated elevated CBF in the left middle cingulate, ventromedial and dorsolateral prefrontal cortex (PFC), compared to SZ-ON (Hedges' g = 0.65-0.91). No difference in hippocampal CBF emerged in SZ-OFF vs. SZ-ON, while SZ-OFF vs. HC showed reduced CBF in the left anterior hippocampus (g = 1.09). Among relatives, REL-P had elevated CBF in the right ventrolateral PFC, compared to REL-NP (g = 0.73) - resembling the "hyperfrontality" effect in SZ-OFF. Conversely, REL-NP vs. HC showed reduced CBF throughout the right PFC (g = 0.52-0.79). Our findings demonstrate unique regional CBF-based activity signatures potentially capturing primary disease effects (SZ-OFF: elevated CBF in PFC but reduced CBF in the anterior hippocampus) vs. antipsychotic effects (SZ-ON: "normalization" of CBF). The observed PFC "hyperactivity" (evidenced by elevated CBF in both SZ-OFF and REL-P) may constitute a regionally-specific "psychosis maker". Future research targeted at granular aspects of hippocampal-PFC pathology in medicated and unmedicated samples may inform more precise, novel interventions in SZ.

Catatonia is a neuropsychiatric syndrome observed in psychiatric and physical conditions. Linked to neuroinflammation, schizophrenia spectrum disorders remain its principal diagnostic context. Short-term outcomes are favourable with prompt treatment. Long-term prognosis remains poorly understood. This systematic review aimed to evaluate long-term outcomes and mortality rates in individuals with catatonia.

Schizophrenia is a complex neurodevelopmental disorder characterized by widespread functional dysconnectivities across the brain. While disturbed temporal dynamics have been reported in schizophrenia, the information flow involving both temporal and spatial dynamics remains unclear. To capture spatio-temporal transition of brain information and to investigate these processes from a neurodevelopmental perspective, we collected resting-state functional MRI (rs-fMRI) data from 86 early-onset schizophrenia (EOS) patients (onset before age 18) and 91 demographically matched typically developing (TD) controls. We employed a non-homogeneous Markov model (NHMM) on dynamic functional connectivities derived from fMRI data. By means of transition probabilities, we modeled the switching of information flow in brain functional networks over time. Stationary probability vectors were used to describe the information convergence distribution of each network, while optimal reachable steps were used to characterize inter-network transmission efficiency. Compared to controls, EOS patients showed significantly increased stationary transition probabilities in the ventral attention network (VAN) and the dorsal attention network (DAN) but decreased probabilities in the default mode network (DMN). In terms of the dynamic interaction characteristics between networks, patients showed increased optimal reachable steps relative to controls, particularly in the VAN-DMN pathway. By integrating NHMM with neuroimaging data, this study revealed VAN- and DMN-involved information transition abnormalities in the early stage of schizophrenia spatio-temporal dynamics, offering novel insights into the developmental pathophysiology of the disorder. Our approach thus provides a novel analytical framework for quantifying spatio-temporal brain dynamics in neurodevelopmental disorders.

This study investigates the diagnostic relationship between schizophrenia and incarceration and elucidates a temporal relationship between these conditions.

Metabolic syndrome (MetS) is common in schizophrenia and drives cardiovascular risk. While cannabis use and potency are increasing, the impact of cannabis on cardiometabolic health in schizophrenia remains unclear. This study assessed the association between objectively measured cannabis use and MetS prevalence in a large schizophrenia cohort.

Previous studies have highlighted the critical role of the complement system in schizophrenia. Dysregulated levels of complement C3 and C4 may affect structural brain networks in schizophrenia, yet their relationship remains unclear. This study aimed to explore the association between peripheral serum levels of complement and the topological properties of individualized morphological similarity networks (MSNs) in first-episode, drug-naïve schizophrenia (FES).

Measuring fidelity to the components of the coordinated specialty care (CSC) model is a critical step in understanding the success of first episode of psychosis (FEP) programs. This study assessed the fidelity of nine Massachusetts CSC programs on a well-validated fidelity measure (the FEP Services Fidelity Scale: FEPS-FS 1.1) and a locally adapted measure (the Massachusetts Psychosis Fidelity Scale: MAPS). Associations between the two fidelity measures were examined, and correlations between fidelity and change in clinical outcomes on the Massachusetts Psychosis Network for Early Treatment assessment battery were explored within 684 clients served through these sites. Overall fidelity of the Massachusetts CSC program with programs in a national study of CSC were also compared on the FEPS-FS. Several fidelity items (weekly team meetings, quick contact with referred clients, and procedural and structural aspects of programs) were related with clinical outcomes, including fewer emergency department visits within the first six months of treatment and client satisfaction at six months (ps < 0.027). Overall CSC fidelity in Massachusetts was significantly higher than the national average (p < .001) and fidelity did not differ between academically and non-academically affiliated sites. The Massachusetts FEP programs had strong fidelity to the CSC model components, higher than national rates. Findings indicate that stronger fidelity may support relapse prevention, as higher fidelity in several key components was related to fewer emergency department visits. This study also highlights the utility of both a thoroughly researched and universal measure of CSC fidelity along with the importance of local adaptations to the measure.

Accelerated brain aging has been consistently reported in patients with schizophrenia. Over the past decade, these findings have been replicated using the Brain Age paradigm, which applies machine learning techniques to estimate brain age from neuroimaging data. This approach yields a single index, the Brain Age Gap, defined as the difference between predicted and chronological age. Nevertheless, both the progressive nature of this phenomenon and the potential role of antipsychotic medication remain unclear. To investigate its progression, we compared the Brain Age Gap between individuals experiencing a first episode of psychosis and healthy controls using ANCOVA, adjusting for age, sex, body mass index, and estimated total intracranial volume. To enhance the robustness of our findings, we employed two distinct models: a transformer-inspired model based on harmonized volumetric brain features extracted with FastSurfer, and a previously trained deep learning model. To assess the potential effect of medication, we further compared bipolar patients who received antipsychotic treatment with those who did not. Mann-Whitney U test consistently showed that medicated bipolar patients did not exhibit a significantly larger Brain Age Gap. Both models converge on the conclusion that accelerated brain aging is unlikely to be explained by antipsychotic medication alone. Longitudinal studies are therefore required to clarify the temporal dynamics of brain aging in schizophrenia.