Schizophr. Res. [JOURNAL]
Sun
200 papers
Antipsychotic-disease duration interaction on glymphatic function in first-episode schizophrenia: Evidence from DTI-ALPS.
Chen H, Xiang H, Zhang M … +4 more , Wen Y, Tang S, Tan S, Xu J
Schizophr Res · 2026 Mar · PMID 41564498 · Publisher ↗
BACKGROUND: The glymphatic system's role in early schizophrenia remains unclear. This study investigated glymphatic function using the DTI-ALPS index in first-episode schizophrenia (FES), exploring its relationships with...
BACKGROUND: The glymphatic system's role in early schizophrenia remains unclear. This study investigated glymphatic function using the DTI-ALPS index in first-episode schizophrenia (FES), exploring its relationships with clinical features, antipsychotic treatment, and cognitive function. METHODS: The study included 37 first-episode drug-naïve (FESDN) patients, 22 first-episode treated (FEST) patients, and 42 demographically matched healthy controls (HCs). ALPS indices were calculated, and clinical assessments included cognitive function (RBANS), psychiatric symptoms (PANSS), and peripheral biomarkers. RESULTS: FES patients exhibited left-hemisphere predominant reductions in ALPS indices (p < 0.01). An interaction was observed between disease duration and treatment: the FEST group had lower DTI-ALPS than the FESDN group in patients with shorter illness durations, but this group difference diminished with longer disease duration (βinter = -0.8 × 10, p < 0.05). The ALPS-cognition association pattern differed between patients and HCs: left ALPS was positively correlated with RBANS in HCs (βHC > 0, p < 0.01) but negatively correlated in FES patients (βFESDN = -16.6, βFEST = -21.6, p < 0.1). Peripheral white blood cell count and total bilirubin were negatively associated with left ALPS in the FEST group (WBC: β = -0.63 × 10, p = 0.025; TBIL: β = -0.80 × 10, p = 0.039), with significant group interaction effects (p < 0.05). CONCLUSION: FES patients demonstrate left-lateralized glymphatic dysfunction, the severity of which is dynamically modulated by treatment and disease duration. The observed negative ALPS‑cognition correlation raises the possibility of a compensatory mechanism in early schizophrenia. Associations noted between peripheral inflammatory/metabolic markers and ALPS offer tentative support for an interactive "periphery-brain" clearance system. DTI-ALPS may serve as a dynamic biomarker reflecting neuropathological mechanisms in early schizophrenia.
Trauma and hallucinations across the sensory modalities: the importance of considering experiences in childhood and adulthood.
Bere M, Rossell SL, Meyer D … +3 more , Nicholls JD, Halperin S, Toh WL
Schizophr Res · 2026 Mar · PMID 41558134 · Publisher ↗
It is widely acknowledged that trauma is related to auditory hallucinations in psychotic disorders. Yet, this relationship has not been well explored in hallucinations across other sensory modalities. The current study i...
It is widely acknowledged that trauma is related to auditory hallucinations in psychotic disorders. Yet, this relationship has not been well explored in hallucinations across other sensory modalities. The current study investigated whether hallucination modality groups (auditory, visual, olfactory, tactile, multisensory) were significantly related to physical, sexual, or emotional trauma. The age at which the trauma was experienced (16 or below, 17 and above) was also considered. Multivariate linear models, analysis of variance, and regression analyses for sixty-six participants with a psychotic disorder sought to determine whether trauma was related to hallucinations. Specifically, we used a modified version of the Life-Stressor Checklist Revised and the Multimodal Hallucinations Schedule (MHS) to identify whether the number of trauma items endorsed, or severity of trauma, at different developmental stages were significantly associated with the severity of lifetime hallucinations across different modalities, and the number of hallucination modalities experienced. We found that the severity of visual hallucinations was significantly associated with a history of sexual trauma. Notably, we revealed that experiencing sexual trauma in both childhood and adulthood was related to an increased self-reported severity of the trauma, and possibly the severity of visual hallucinations. These preliminary findings suggest that type of trauma may be uniquely related to specific hallucination modality and severity. Further, it is important to consider adulthood traumas as well as those occurring in childhood. These results have implications for clinical assessment and intervention.
Prevalence and multidimensional impact of sarcopenia in schizophrenia: Associations with oxidative stress, functioning, and symptom severity.
Şişman Ö, Önen S
Schizophr Res · 2026 Mar · PMID 41548363 · Publisher ↗
OBJECTIVE: This study aimed to investigate the prevalence of sarcopenia in individuals with schizophrenia and examine its associations with oxidative stress, symptom severity, functioning, and quality of life. METHODS: A...
OBJECTIVE: This study aimed to investigate the prevalence of sarcopenia in individuals with schizophrenia and examine its associations with oxidative stress, symptom severity, functioning, and quality of life. METHODS: A total of 198 schizophrenia patients aged 18-65 were assessed using the EWGSOP2 criteria for sarcopenia. Participants were classified as sarcopenic if they met criteria for probable, confirmed, or severe sarcopenia. Oxidative stress was evaluated using total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI). Clinical functioning, psychiatric symptoms, and quality of life were assessed using standardized psychometric tools. Multiple linear regression was conducted to identify predictors of oxidative stress parameters. RESULTS: Sarcopenia was identified in 66.6% of participants, with most meeting criteria for probable sarcopenia. Sarcopenic patients had significantly lower muscle mass, bone mass, basal metabolic rate, handgrip strength, and walking speed, along with poorer quality of life and functional scores. TAC positively correlated with muscle-related parameters and inversely with sarcopenia severity, while OSI showed negative correlations with physical health indicators. Sarcopenic patients also had more severe psychiatric symptoms. Regression analysis revealed that TAC was significantly predicted by BMI, the number of sarcopenia criteria met, PANSS-Total, and WHOQOL-BREF scores (R = 0.10, p = .011). No significant differences were found in mean TAC, TOS, and OSI between sarcopenic and non-sarcopenic groups. CONCLUSION: Sarcopenia is highly prevalent and clinically relevant in individuals with schizophrenia, even at midlife. Routine screening and early interventions targeting physical health and oxidative stress may improve outcomes.
Perceptual organization and its visual subcomponents in schizophrenia and schizotypy: A systematic review.
Cessa R, Ghiani A, Cenk E … +1 more , Bertamini M
Schizophr Res · 2026 Mar · PMID 41547030 · Publisher ↗
Perceptual organization (PO) deficits have long been considered a hallmark of schizophrenia (SZ), reflecting disruptions in the integration of visual information. This systematic review critically evaluates the behaviora...
Perceptual organization (PO) deficits have long been considered a hallmark of schizophrenia (SZ), reflecting disruptions in the integration of visual information. This systematic review critically evaluates the behavioral evidence for PO impairments in SZ and individuals with high schizotypal traits, focusing on three key mid-level processes: contour integration, perceptual grouping, and figure-ground segmentation. Forty-four studies were included, identified through a systematic search and evaluated for bias using the QUADAS-2 tool. Findings reveal robust and replicable deficits in contour integration among individuals with SZ, especially in those with disorganization symptoms, suggesting impaired lateral interactions in early visual areas. Perceptual grouping deficits were also prominent but appeared more sensitive to cognitive load and stimulus complexity, consistent with top-down integration failures. Figure-ground segmentation impairments were less consistently reported and often dependent on task demands, emerging more clearly under challenging conditions. In schizotypy, evidence of PO deficits was more variable. Some studies identified subtle impairments in contour integration and grouping, particularly under high attentional load or in individuals with disorganized traits, while others reported intact performance. The heterogeneity of methods across studies, particularly differences in stimulus type, complexity, and grouping cues, was a major limiting factor for cross-study comparisons. Findings from this review support a dimensional view of PO deficits, where specific symptom clusters, rather than diagnosis alone, predict perceptual dysfunction. PO impairments, particularly in contour integration, may serve as sensitive cognitive markers for early detection and targeted intervention in SZ-spectrum disorders.
Randomized double-blind inpatient study of a gluten-free diet for negative symptoms in people with schizophrenia.
Kelly DL, Lee CM, Vyas G … +18 more , Buchanan RW, Roche DJ, Harrington V, Rowland LM, Wijtenburg SA, Adhikari BM, Sathyasaikumar KV, Kochunov P, Talor MV, Waltz J, Liu F, Hare S, Adams HA, Schwarcz R, Salem D, Gold JM, Clark SM, Eaton WW
Schizophr Res · 2026 Mar · PMID 41544406 · Publisher ↗
BACKGROUND: There are no FDA-approved treatments for negative symptoms in schizophrenia and related disorders (SRD). In an SRD subgroup with systemic and central inflammation and elevated anti-gliadin immunoglobulin G an...
BACKGROUND: There are no FDA-approved treatments for negative symptoms in schizophrenia and related disorders (SRD). In an SRD subgroup with systemic and central inflammation and elevated anti-gliadin immunoglobulin G antibodies (AGA IgG+), previous findings suggested that a gluten-free diet (GFD) improved negative symptoms. METHODS: We conducted a five-week double-blind randomized placebo-controlled inpatient trial comparing a GFD versus a gluten-containing diet (GCD) in people with SRD and elevated AGA IgG+ (N = 39; n = 21 GFD and n = 18 GCD). The Clinical Assessment Interview for Negative Symptoms Motivation and Pleasure (CAINS MAP) scale measured the primary outcome of negative symptoms. Secondary outcomes evaluated other symptom domains and serum kynurenine pathway metabolites. Also, we explored inflammatory markers and, in n = 20 participants, measured cerebral blood flow (CBF) using Arterial Spin Labeling, and neurochemistry using magnetic resonance spectroscopy. OUTCOMES: Relative to a GCD, a GFD was associated with a modest decrease in CAINS MAP scores (df = 31.2.1, F = 2.96, p = 0.035); decrease in kynurenic acid (KYNA; df = 32, F = 9.51, p = 0.0042) and kynurenine (df = 32, F = 11.45, p = 0.0019); and increase in CBF and total creatine in frontal brain regions. KYNA and CAINS MAP change scores were correlated (r = 0.350, p = 0.039) while cognition was not impacted. DISCUSSION: Our preliminary data suggests that a GFD may be associated with modest improvements on experiential negative symptoms within an SRD subgroup. A GFD may be associated with reductions in kynurenine pathway metabolites and increased CBF. Larger and longer studies are needed to confirm negative symptom efficacy in this AGA IgG+ SRD subgroup.
A multimodal fusion analysis of structural and functional abnormalities in acute onset treatment-resistant schizophrenia.
Cao P, Han Y, Zou L … +4 more , Gao S, Xu Q, Xiao C, Xu X
Schizophr Res · 2026 Mar · PMID 41544405 · Publisher ↗
BACKGROUND: Patients with treatment-resistant schizophrenia (TRS) experience more severe clinical symptoms, which may derive from greater structural and functional brain abnormalities compared to non-TRS. However, the ne...
BACKGROUND: Patients with treatment-resistant schizophrenia (TRS) experience more severe clinical symptoms, which may derive from greater structural and functional brain abnormalities compared to non-TRS. However, the neural underpinnings of TRS remain poorly understood, and conventional unimodal neuroimaging approaches are limited in capturing cross-modal interactions. Therefore, we used multimodal fusion via multiset canonical correlation and joint independent component analysis (mCCA+jICA) to integrate MRI data to examine shared and modality-specific features in TRS. Methods65 TRS patients, 65 non-TRS patients, and 54 healthy controls (HCs) underwent 3 T MRI. Structural MRI and resting-state functional MRI data were preprocessed using DPARSFA, and grey matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) maps were extracted. The mCCA+jICA was performed to derive joint independent components (ICs) and subject-specific mixing coefficients. Group differences in mixing coefficients were assessed via MANCOVA, and clinical correlations were evaluated using partial correlations. RESULTS: Patients showed significant differences in mixing coefficients for one modality-specific group-discriminative IC (GMV-IC3) and two joint group-discriminative ICs (ReHo-IC6, and GMV-IC6) compared to HCs. These components also differentiated TRS from non-TRS, with abnormalities concentrated in the precuneus in both ReHo and GMV. Partial correlation analysis revealed significant positive associations between the mixing coefficients of GMV-IC3, GMV-IC6, and total PANSS scores and CPZ equivalents specifically in the TRS group. CONCLUSIONS: This study demonstrates that co-existing structural and functional brain alterations are associated with the pathophysiology of TRS, highlighting their potential as novel multimodal biomarkers.
Frailty and fall risk in schizophrenia: Which components drive the risk of falls?
Sugisaki T, Sugawara N, Shinozaki M … +4 more , Yokoyama N, Yoshida R, Kawamata Y, Yasui-Furukori N
Schizophr Res · 2026 Mar · PMID 41534363 · Publisher ↗
OBJECTIVES: Frailty is increasingly recognized in schizophrenia and is linked to adverse outcomes such as fall. However, mechanisms connecting body composition to frailty and fall risk in psychiatric inpatients remain in...
OBJECTIVES: Frailty is increasingly recognized in schizophrenia and is linked to adverse outcomes such as fall. However, mechanisms connecting body composition to frailty and fall risk in psychiatric inpatients remain insufficiently understood. This study aimed to examine (1) the association between fat-free mass and frailty; (2) the relationship between frailty and fall in the past 12 months; and (3) which frailty components most strongly relate to fall among inpatients with schizophrenia. METHODS: In this cross-sectional study, 195 hospitalized adults (≥40 years; mean age 65.9 years) with schizophrenia or schizoaffective disorder were assessed. Frailty was defined using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. Body composition was measured by bioelectrical impedance analysis to compute fat-free mass index (FFMI) and fat mass index (FMI). RESULTS: Frailty prevalence was 32.8% (prefrail 54.9%; robust 12.3%). Higher FFMI was independently associated with lower odds of being frail. Frailty was strongly associated with fall history (OR = 9.85 vs. prefrail/robust). Across individual frailty components, slowness (reduced gait speed) showed the strongest relationship with fall. CONCLUSIONS: Frailty is highly prevalent among inpatients with schizophrenia and strongly predicts fall risk. Among the individual frailty components, slowness was the key driver of fall, pointing to gait impairment as a critical focus for intervention. Routine gait assessment, combined with physiotherapy, nutritional support, and careful medication review, may help reduce frailty and prevent fall in this population. Prospective studies are needed to confirm these associations and to establish effective strategies for fall prevention in schizophrenia.
Magnetic seizure therapy preserves delayed memory and 40-Hz auditory steady-state responses compared with electroconvulsive therapy in schizophrenia.
Hong Y, Jiang J, Li J … +7 more , Tang X, Jiao X, Qian Z, Tang Y, Zhang T, Li C, Wang J
Schizophr Res · 2026 Mar · PMID 41534362 · Publisher ↗
BACKGROUND: Electroconvulsive therapy (ECT) is effective for schizophrenia but often impairs delayed memory, whereas magnetic seizure therapy (MST) typically spares cognition. We investigated whether these modalities dif...
BACKGROUND: Electroconvulsive therapy (ECT) is effective for schizophrenia but often impairs delayed memory, whereas magnetic seizure therapy (MST) typically spares cognition. We investigated whether these modalities differentially affect 40-Hz auditory steady-state responses (ASSR)-a marker of gamma synchrony critical for memory-and if these changes predict cognitive outcomes. METHODS: This study is a secondary analysis of a randomized clinical trial for schizophrenia comparing ECT (n = 16) and MST (n = 17). Clinical symptoms and cognition were assessed using Positive and Negative Syndrome Scale (PANSS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline and after 10 treatment sessions. 40-Hz ASSR were recorded via EEG at baseline and after the first treatment session. RESULTS: Both treatments improved psychotic symptoms. However, ECT induced cognitive deficits (particularly delayed memory) and significant reductions in acute ASSR power and phase-locking. In contrast, MST preserved both cognitive function and ASSR integrity. Notably, within the ECT group, greater acute suppression of ASSR power predicted better preservation of delayed memory. CONCLUSION: MST demonstrates a superior safety profile compared to ECT, preserving both gamma synchrony and memory. The association between acute gamma suppression and better memory retention in ECT suggests this reduction may be an adaptive physiological response. Thus, early ASSR changes may serve as a predictive biomarker for cognitive tolerability.
Antipsychotic use and associating factors among persons with substance-induced psychosis and first-episode psychotic disorder- A nationwide register-linkage study.
Jeyapalan J, Taipale H, Tanskanen A … +3 more , Tiihonen J, Mittendorfer-Rutz E, Niemelä S
Schizophr Res · 2026 Mar · PMID 41529437 · Publisher ↗
BACKGROUND: Antipsychotic use after first-episode psychotic disorder (FEPD) has been widely studied, but data on substance-induced psychosis (SIP) are lacking. OBJECTIVES: To examine the prevalence and associated factors...
BACKGROUND: Antipsychotic use after first-episode psychotic disorder (FEPD) has been widely studied, but data on substance-induced psychosis (SIP) are lacking. OBJECTIVES: To examine the prevalence and associated factors of antipsychotic use in individuals with incident SIP compared to a matched FEPD cohort. METHODS: From Swedish healthcare registers, 7320 incident SIP cases (2006-2016) were identified and matched 1:1 by age, sex, and year with FEPD cases. The point prevalence of antipsychotic use was assessed biannually from three years before to three years after the incident diagnosis. Associations between any antipsychotic use during one year post-diagnosis and sociodemographic, clinical, and work-related factors were estimated using modified Poisson regression to obtain unadjusted and age- and sex-adjusted risk ratios (RRs) with 95% CIs. This register-based analysis followed RECORD reporting standards. RESULTS: The point prevalence of antipsychotic use peaked six months after the first psychotic episode (23% in SIP vs 54% in FEPD) and remained approximately stable thereafter (20% vs 50% at three years). During the first year, the cumulative prevalence of any antipsychotic use was 43% in SIP and 73% in FEPD. Among SIP patients, younger age, female sex, non-European origin, and prior psychiatric comorbidity particularly anxiety, depression, ADHD, and personality disorders were the strongest correlates of antipsychotic use. Functional impairment indicators such as long-term sickness absence and disability pension were also associated with increased use. In FEPD, age, depression, autism-spectrum diagnosis, and short-term sickness absence showed similar but weaker patterns. Olanzapine was the most commonly used antipsychotic in both cohorts. CONCLUSIONS: Despite diagnostic definitions describing SIP as transient, a substantial proportion of patients continued antipsychotic treatment beyond the acute phase. These findings emphasise that younger age, psychiatric comorbidity, and psychosocial vulnerability strongly influence prescribing decisions in SIP and highlight the need for evidence-based, subtype-specific treatment guidelines.
Association between negative symptoms and health-related quality of life and functional outcomes in persons with schizophrenia: A systematic review.
Chan A, Lu A, Menon T … +5 more , Wong S, Valentino K, Le GH, Dri CE, McIntyre RS
Schizophr Res · 2026 Feb · PMID 41512718 · Publisher ↗
BACKGROUND: Negative symptoms in schizophrenia (SCZ) are core phenomenological characteristics known to affect health-related quality of life (HRQoL) and functioning. This systematic review aims to synthesize extant lite...
BACKGROUND: Negative symptoms in schizophrenia (SCZ) are core phenomenological characteristics known to affect health-related quality of life (HRQoL) and functioning. This systematic review aims to synthesize extant literature to evaluate/elucidate the effect of negative symptoms on HRQoL and functional outcomes in persons with SCZ, as well as to better understand the association between HRQoL and functional outcomes. METHOD: A systematic search was conducted from inception to July 24, 2025, using Pubmed, MedLine, Embase, AMED, PsychInfo, and Scopus. All studies were independently screened by three reviewers (A.C., A.L., T.M.). Primary studies reporting on the association between negative symptoms, HRQoL, and/or functional outcomes in persons with SCZ were included. RESULTS: We included 68 relevant studies. Most studies were observational and cross-sectional, while others employed case-control, before-after without control, or randomized controlled trial designs. A consistent, small, negative correlation was observed between the presence and severity of negative symptoms and HRQoL (r = -0.67 to 0.69), as well as functional outcomes (r = -0.85 to 0.63. A slight positive association was found between functional outcomes and HRQoL (r = -0.63 to 0.58). CONCLUSION: Our findings underscore the significant impact of negative symptoms on critical patient-reported outcomes, including HRQoL and functional outcomes. Notwithstanding their clinical importance, there is limited research on negative symptoms, and more research is needed on treatments that address negative symptoms directly, emphasizing the urgent need for targeted therapeutic development.
Long-term efficacy, safety, and tolerability of xanomeline and trospium chloride in schizophrenia: A 52-week, open-label trial (EMERGENT-5).
Kaul I, Claxton A, Chaturvedi S … +4 more , Patel T, Wu H, Sawchak S, Sauder C
Schizophr Res · 2026 Feb · PMID 41506001 · Publisher ↗
BACKGROUND: The M/M muscarinic receptor agonist xanomeline combined with the peripherally restricted pan-muscarinic receptor antagonist trospium chloride is the first approved treatment for adults with schizophrenia with...
BACKGROUND: The M/M muscarinic receptor agonist xanomeline combined with the peripherally restricted pan-muscarinic receptor antagonist trospium chloride is the first approved treatment for adults with schizophrenia with no direct D dopamine receptor blockade. Xanomeline and trospium chloride (KarXT) reduced symptoms and was generally well tolerated in adults with schizophrenia in three, 5-week, randomized, double-blind, placebo-controlled trials and a 52-week, open-label extension trial. METHODS: EMERGENT-5 (NCT04820309) was a 52-week, open-label trial evaluating the long-term safety, tolerability, and efficacy of twice daily KarXT (maximum dose 125/30 mg) in psychiatrically stable adults with schizophrenia. Safety measures included treatment-emergent adverse events (TEAEs), vital signs, and laboratory parameters. Efficacy measures included change in Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGIS). RESULTS: Between June 2021-May 2024, 566 participants at 54 US sites received ≥1 dose of KarXT. Overall, 277/566 (48.9 %) participants completed the trial. A total of 466/566 (82.3 %) experienced ≥1 TEAE, the majority of which were mild or moderate in intensity; severe TEAEs were reported in 33/566 (5.8 %) participants. The most common TEAEs occurring in ≥5 % of participants were nausea (23.1 %), vomiting (20.3 %), constipation (18.0 %), hypertension (10.4 %), diarrhea and dry mouth (9.4 % each), dizziness (8.8 %), headache (8.1 %), dyspepsia (7.2 %), somnolence (6.2 %), weight decreased (5.7 %), and hyperhidrosis (5.1 %). KarXT improved PANSS total, PANSS positive and negative subscale, and CGI-S scores over the trial duration. CONCLUSIONS: Psychiatrically stable adults with schizophrenia were safely switched from prior antipsychotics to KarXT with a trend toward symptom improvement over 1 year. The safety and tolerability profile of KarXT was consistent with observations in prior clinical trials; no new safety issues emerged.
Predictions of different elements of everyday functional outcomes in bipolar disorder and schizophrenia: Cognition, social cognition, clinical symptoms, and mood states as predictors.
Neff MA, Raffensperger KV, Moore RC … +4 more , Depp CA, Ackerman RA, Pinkham AE, Harvey PD
Schizophr Res · 2026 Feb · PMID 41483637 · Full text
BACKGROUND: Disability is common in serious mental illnesses across employment, everyday activities, and social outcomes. Although cognition and social cognition are known to predict disability, the level of influence ac...
BACKGROUND: Disability is common in serious mental illnesses across employment, everyday activities, and social outcomes. Although cognition and social cognition are known to predict disability, the level of influence across elements of functioning and condition and is not certain. We examined the correlations between cognition and social cognition, measured with observer ratings and performance, with ratings of performance in employment, everyday activities, and social outcomes in a transdiagnostic sample. METHODS: Participants with bipolar disorder (BD; n = 114) and SZ (SZ; n = 126) were studied. Everyday functioning was indexed with observer ratings of functioning, consolidating self and informant reports. In order to evaluate the usefulness of additional information sources, predictors also included clinical symptoms in domains of psychosis, negative symptoms, and depression, and momentary data on moods, location, and social context collected over 30 days of Ecological Momentary Assessment (EMA). RESULTS: Observer ratings of neurocognition and social cognition were uniformly correlated with functioning across diagnoses, with performance-based tests less strongly correlated with outcomes. Negative symptoms were the best predictor of interpersonal functioning, with mood symptoms also predictive in BD. IMPLICATIONS: Observer-rated social cognition emerged as the most consistent predictor of disability across all domains and diagnoses. Negative symptoms had a relatively specific contribution to interpersonal outcomes, with sadness also contributing in BD. As observer ratings of social cognition and cognition were better predictors of outcomes than performance based tests, this may suggest a practical assessment strategy in general clinical settings with limited access to testing specialists.
Schizotypal traits and daily social functioning: Insights from ecological momentary assessment.
Russell MT, Wu W, Salyers MP … +6 more , Filip TF, Akhras S, Busanet H, McCleery A, Thakkar KN, Minor KS
Schizophr Res · 2026 Feb · PMID 41483636 · Publisher ↗
Elevated schizotypal traits are a risk factor for developing schizophrenia and other forms of psychopathology. Because schizophrenia is marked by social functioning difficulties, examining how schizotypal traits shape ev...
Elevated schizotypal traits are a risk factor for developing schizophrenia and other forms of psychopathology. Because schizophrenia is marked by social functioning difficulties, examining how schizotypal traits shape everyday interactions can clarify early risk processes. Although ecological momentary assessment (EMA) has been used to examine social interaction likelihood (how often people interact), depth (complexity of content in interactions), and enjoyment (pleasure derived from interactions) in people with schizophrenia, few have explored differences in social interactions across schizotypal traits (positive, negative, and disorganized). This study used EMA to evaluate how positive, negative, and disorganized schizotypal traits in college students (n = 185) relate to social interaction likelihood, depth, and enjoyment in daily life. Given their established role in social functioning and their complex relationships with schizotypal traits, we also investigated whether affect and stress predict individuals' concurrent likelihood, depth, and enjoyment of social interactions. Results revealed that negative traits more strongly predicted reduced social interaction likelihood (B = -0.02, p = .04) and enjoyment (B = -0.06, p < .01) compared to positive (likelihood: B = 0.01, p = .37; enjoyment: B = 0.03, p = .02) and disorganized (likelihood: B = 0.00, p = .85; enjoyment: B = -0.04, p = .04) traits. Contrary to hypotheses, positive affect emerged as the strongest predictor of social interaction outcomes, surpassing negative affect and stress. Additionally, we observed a significant interaction between positive schizotypal traits and negative affect (B = -0.01, p = .03), such that individuals higher in positive traits showed a stronger reduction in enjoyment when experiencing negative affect. These findings enhance our understanding of how schizotypal traits and affect impact daily social interactions and may inform future personalized interventions designed to improve social functioning deficits in at-risk individuals.
Improving systems & communities of psychosis care: Proceedings from the 2024 Mass-STEP Conference.
Imam I, Johnson KA, Saluja A … +4 more , Mesholam-Gately RI, Guyer ME, Ongur D, Keshavan MS
Schizophr Res · 2026 Feb · PMID 41475222 · Publisher ↗
A 2024 conference titled "Early Intervention in Psychosis: Systems & Communities of Care" brought together researchers, clinicians, policy experts, and individuals with lived experience to discuss and guide updates in ea...
A 2024 conference titled "Early Intervention in Psychosis: Systems & Communities of Care" brought together researchers, clinicians, policy experts, and individuals with lived experience to discuss and guide updates in early intervention (EI) for psychosis in Massachusetts. The first day emphasized the translation of research to practice, highlighting innovative projects such as culturally responsive care models, data-driven quality improvement, and novel applications of machine learning. The second day focused on system-level strategies, including equity in coordinated specialty care, peer-led initiatives, and sustainable financing through team-based billing codes. Lived experience voices were central throughout, emphasizing the importance of mutuality, inclusivity, and responsiveness in care. These proceedings underscore the value of community-engaged strategic planning and cross-sector collaboration in strengthening psychosis care, and reflect a maturing ecosystem of EI services committed to improving access, equity, and long-term outcomes for individuals experiencing psychosis.
Psychotic-like experiences, suicidal thoughts and behaviours, and non-suicidal self-injury in young offenders.
Stickley A, Isaksson J, Koposov R … +2 more , Sumiyoshi T, Ruchkin V
Schizophr Res · 2026 Feb · PMID 41468705 · Publisher ↗
BACKGROUND: Research has indicated that both suicidal thoughts and behaviours (STBs) and the prevalence of psychotic-like experiences (PLEs) are elevated in incarcerated young offenders. However, as yet, there has been n...
BACKGROUND: Research has indicated that both suicidal thoughts and behaviours (STBs) and the prevalence of psychotic-like experiences (PLEs) are elevated in incarcerated young offenders. However, as yet, there has been no research on the PLEs-STBs association in this population. To address this research gap, the current study examined the association between PLEs and STBs (i.e., suicidal ideation and suicide attempts), and non-suicidal self-injury (NSSI) in a sample of male adolescents who were incarcerated in Northern Russia. METHODS: Semi-structured psychiatric interviews and self-reports were used to obtain information from 370 young offenders aged 14 to 19 (mean age 16.4 years). The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) was used to assess PLEs, STBs, NSSI, and co-occurring psychiatric disorders. Binary and ordinal logistic regression were used to assess associations. RESULTS: Almost one-third of the sample (31.6 %) had lifetime PLEs. Lifetime PLEs were significantly associated with STBs in an analysis that also included psychiatric disorders (OR = 1.79). A similar result was obtained for the association between PLEs and NSSI (OR = 2.02), when co-occurring psychiatric disorders were included in the analysis. CONCLUSIONS: PLEs were prevalent in this sample of male adolescents serving custodial sentences and associated with higher odds of both STBs and NSSI. Screening for PLEs in the context of broader mental health assessments and interventions during institutional placement may be important for reducing STBs and NSSI in this population.
Is it the end of the clozapine world as we know it? Perspectives on social implications of REMS elimination.
Uehling M, Hamm D, Goldsmith D … +1 more , Brown J
Schizophr Res · 2026 Feb · PMID 41443002 · Publisher ↗
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S100A8 dysregulation as a neuroimmune nexus: Bridging childhood inflammatory infections to adult schizophrenia-like behaviors via the ELNI model.
Tengfei C, Shiyu W, Longyu S … +10 more , Lei C, Ni F, Yaoyu W, Jianing Z, Qing L, Kang L, Jie L, Yahaya BHB, Lin J, Li W
Schizophr Res · 2026 Feb · PMID 41443001 · Publisher ↗
OBJECTIVE: Emerging evidence suggests that dysregulated neuroimmune pathways are implicated in schizophrenia (SCZ); however, the mechanisms connecting early-life inflammation to adult psychiatric outcomes remain inadequa...
OBJECTIVE: Emerging evidence suggests that dysregulated neuroimmune pathways are implicated in schizophrenia (SCZ); however, the mechanisms connecting early-life inflammation to adult psychiatric outcomes remain inadequately understood. This study examines the role of the pro-inflammatory alarmin S100A8, a calcium- and zinc-binding protein that significantly influences the regulation of inflammatory processes and immune responses, as a potential convergent hub in pediatric infections and SCZ. Furthermore, the study characterizes the behavioral effects of S100A8 using a novel ELNI model. METHODS: We analyzed gene expression datasets from blood and brain of SCZ patients and pediatric infections (GEO accessions: GSE53987, GSE73464, GSE38484) using limma. Genetic regulation of S100A8 was examined by integrating GWAS (PGC-SCZ3) and TWAS (PsychENCODE) data. An ELNI mouse model was established via LPS injections on postnatal days 24-30. Behavioral tests, qRT-PCR, and immunofluorescence were used to assess neuroinflammation and behavioral phenotypes. RESULTS: S100A8 was upregulated in the blood and postmortem brain tissues of SCZ patients, as well as in the blood of children with bacterial infections. The rs10908557 risk allele was associated with increased S100A8 expression. LPS-induced early-life inflammation in mice led to transient growth impairment, prepulse inhibition deficits, and depressive-like behaviors. S100A8 overexpression in the hippocampus correlated with microglial activation and impaired sensorimotor gating. CONCLUSION: S100A8 serves as a shared genetic and transcriptional biomarker between pediatric infections and SCZ. Early-life inflammation induces persistent SCZ-relevant behaviors through S100A8-mediated neuroinflammation. The ELNI model offers a translational platform for studying neurodevelopmental origins of psychiatric disorders, highlighting S100A8 as a potential biomarker and therapeutic target.
Pharmacokinetic correlates of clinical response in a retrospective naturalistic cohort of patients treated with long-acting injectable antipsychotics.
Kuzo N, Gaspari D, Carpi F … +4 more , Hiemke C, Paulzen M, Conca A, Schoretsanitis G
Schizophr Res · 2026 Feb · PMID 41443000 · Publisher ↗
OBJECTIVE: To investigate the pharmacokinetic correlates of clinical response to long acting injectable (LAI) antipsychotics in a naturalistic outpatient sample. METHODS: We conducted a retrospective cohort study of LAI-...
OBJECTIVE: To investigate the pharmacokinetic correlates of clinical response to long acting injectable (LAI) antipsychotics in a naturalistic outpatient sample. METHODS: We conducted a retrospective cohort study of LAI-treated outpatients. Steady-state trough antipsychotic plasma concentrations were classified as subtherapeutic, within, or supratherapeutic based on established therapeutic reference ranges (TRRs). Clinical response was defined as Clinical Global Impression Improvement score ≤ 2. Generalized linear mixed models were used to analyze predictors of treatment response. RESULTS: In a total of 158 LAI-treated outpatients, responders (42.4 %) were significantly younger (50.5 vs. 55.6 years, p = 0.002) and more often treated with monotherapy (64.2 % vs. 44.0 %, p = 0.01). Half of the responders (51.1 %) had antipsychotic levels below the TRR (51.1 %), and 42.2 % had levels within TRR, while there were no responders with supratherapeutic concentrations (p = 0.01). After controlling for age, sex, body mass index, smoking, LAI monotherapy, and symptom severity, patients with subtherapeutic plasma concentrations (adjusted odds ratio (aOR): 31.97, 95 % confidence interval (CI): 1.74-588.55, p = 0.02) and with levels within the TRR (aOR: 23.01, 95 % CI: 1.28-414.48, p = 0.03) had higher probability of treatment response compared to those with supratherapeutic concentrations, while these estimates were limited by the small group size (n = 9). Younger age (aOR: 0.97, 95 % CI: 0.94-0.99, p = 0.04) and LAI monotherapy (aOR = 3.77, 95 % CI = 2.19-6.51, p = 0.001) were associated with better treatment response. CONCLUSIONS: Assessing antipsychotic concentrations combined with clinical characteristics such as LAI monotherapy and age may be useful for guiding pharmacotherapy with LAIs.
Use and outcomes of antipsychotic medications for delusional and paranoid personality disorders: A population-based study.
Gonzalo-deMiguel A, Abascal-Peiró S, Prescription Study Group … +2 more , Martínez-Alés G, Baca-García E
Schizophr Res · 2026 Feb · PMID 41435532 · Publisher ↗
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Dual glymphatic roles in first-episode schizophrenia and clinical high-risk for psychosis: Evidence from diffusion tensor image analysis along the perivascular space index.
Peng S, Geng X, Huen WWK … +8 more , Fang CZ, Chan JKN, Chu RST, Chen EY, Chan SKW, Lee EHM, Hui CLM, Chang WC
Schizophr Res · 2026 Feb · PMID 41435531 · Publisher ↗
INTRODUCTION: Emerging evidence has implicated glymphatic dysfunction in schizophrenia-spectrum disorders (SSD), yet its role during early stages of the disease remains unclear. To clarify its involvement in pathophysiol...
INTRODUCTION: Emerging evidence has implicated glymphatic dysfunction in schizophrenia-spectrum disorders (SSD), yet its role during early stages of the disease remains unclear. To clarify its involvement in pathophysiological mechanisms in the early illness course, we evaluated glymphatic function in first-episode SSD (FES) and clinical high-risk for psychosis (CHR-P) populations using diffusion-tensor image analysis along perivascular space (DTI-ALPS) index, testing whether it would exhibit progressive deterioration or transient compensatory adaptation. METHODS: We examined 55 FES patients, 23 individuals with CHR-P and 30 healthy controls (HCs). ANCOVAs were conducted on the global and bilateral DTI-ALPS indices across the three groups, adjusting for age, sex, and head motion. Partial correlation analyses further examined associations between DTI-ALPS index and measures on severity of various symptom dimensions, functioning, and cognitive performance of FES and CHR-P samples. RESULTS: After controlling for covariates, group comparisons revealed that FES patients showed significantly lower global and bilateral DTI-ALPS indices than HCs, while CHR-P did not differ from HCs. Antipsychotic dosage and FES diagnostic subtypes showed no significant differences in DTI-ALPS indices. Correlation analyses showed that, after correction for multiple comparisons, ALPS indices showed no significant correlations with symptoms or cognitive performance. But in the uncorrected analyses, the FES and CHR-P groups showed opposite patterns of correlations with symptoms and cognition. CONCLUSIONS: These findings indicate that glymphatic dysfunction is a prominent feature of FES, while early signs of dysfunction may already be present during the prodromal stage. DTI-ALPS index show potential as a stage-specific marker pending longitudinal validation and replication.
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