Parental schizophrenia is associated with various adverse developmental outcomes in offspring, including neurodevelopmental impairments and elevated physical injury risks. However, limited evidence is available regarding the association between parental schizophrenia and fracture risk in offspring, particularly during adolescence-a developmental stage characterized by increased susceptibility to fractures. In this study, we investigated whether parental schizophrenia influences the risk of fractures in offspring.

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.

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 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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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).

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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.