Schizophrenia Research最新文献

{"title":"The association between childhood Toxoplasma gondii, psychotic experiences and grey matter volume: A population-based cohort study","authors":"Jehanita Jesuthasan ,&nbsp;Kate Merritt ,&nbsp;Francesca Solmi ,&nbsp;Pedro Luque Laguna ,&nbsp;Anthony S. David","doi":"10.1016/j.schres.2026.01.022","DOIUrl":"10.1016/j.schres.2026.01.022","url":null,"abstract":"<div><div><em>Toxoplasma gondii</em> (<em>T. gondii</em>), a parasite that can be transmitted to humans by cats, has been proposed as a modifiable risk factor for schizophrenia and related disorders. However, much of the research examining this relationship has relied on cat ownership as a proxy measure for <em>T. gondii</em> exposure. This study examined the relationship between serum <em>T. gondii</em> levels and later psychotic experiences (PEs) and brain volume. We also explored the relationship between cat ownership and <em>T. gondii</em> serology. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 3542 individuals for whom data on serum <em>T. gondii</em> during childhood and PEs at age 18 were available. Voxel-based morphometry assessed whether MRI measures of grey matter volume at age 20 were associated with <em>T. gondii</em> levels among a subset of the participants (<em>N</em> = 334). Serum <em>T. gondii</em> was not associated with PE group in adjusted models (suspected PEs risk ratio (<em>RR</em>) = 1.06, 95% confidence interval (CI) [0.89–1.27]; definite PEs <em>RR</em> = 0.86, 95% CI [0.65–1.13]; psychotic disorder <em>RR</em> = 1.00, 95% CI [0.73–1.38]). Exposure to cats during gestation was associated with higher <em>T. gondii</em> in adolescence (<em>β</em> = 0.08, <em>p</em> = 0.033), while exposure to cats during childhood was not (<em>β</em> = 0.05, <em>p</em> = 0.310). <em>T. gondii</em> was not associated with grey matter volume in the neuroimaging sample (<em>pFWEs</em> ≥ 0.882, <em>Zs</em> ≤ 3.86). Future work examining the relationship between <em>T. gondii</em> and schizophrenia-spectrum disorders should focus on serology or cat ownership during gestation as a proxy measure of <em>T. gondii</em> exposure, as there was no association between childhood cat ownership and <em>T. gondii</em>.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 65-72"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Executive function mediates the effects of genetic liability to schizophrenia on behavior and functioning in a community sample of children and adolescents","authors":"Lais Fonseca ,&nbsp;Lucas Toshio Ito ,&nbsp;Carolina Ziebold ,&nbsp;Luis A. Rohde ,&nbsp;Eurípedes C. Miguel ,&nbsp;Rodrigo A. Bressan ,&nbsp;Pedro M. Pan ,&nbsp;Sintia I. Belangero ,&nbsp;Marcos L. Santoro ,&nbsp;Felipe V. Gomes ,&nbsp;Anthony A. Grace ,&nbsp;Ary Gadelha","doi":"10.1016/j.schres.2026.01.014","DOIUrl":"10.1016/j.schres.2026.01.014","url":null,"abstract":"<div><h3>Background</h3><div>Genetic liability for schizophrenia has been associated with cognitive deficits and clinical phenotypes during neurodevelopment. However, the possible role of executive function (EF) as a mediator between the polygenic risk score for schizophrenia (PRS-SZ) and subsequent outcomes, including transdiagnostic general psychopathology (the p-factor), has yet to be examined. In this study, we investigated whether EF mediates the effect of PRS-SZ on psychopathology and functional phenotypes in a community-based youth sample.</div></div><div><h3>Study design</h3><div>We analyzed cross-sectional data from 698 participants (aged 6–14) of the Brazilian High-Risk Cohort. PRS-SZ was calculated using summary statistics from the Psychiatric Genetics Consortium (PGC-3). EF was assessed through working memory, inhibitory control, and time processing tasks, condensed into a single latent EF trait. Independent linear models were tested to examine direct associations between PRS-SZ and EF, general psychopathology, anxiety symptoms, psychotic experiences (PE), and school performance. Mediation models were applied to evaluate EF as a mediator of the associations between PRS-SZ and each outcome.</div></div><div><h3>Study results</h3><div>PRS-SZ predicted lower EF scores (β = −0.091, <em>t</em> = −2.435, <em>p</em> = 0.015). No direct associations were found between PRS-SZ and the other measures. EF mediated the association between PRS-SZ and general psychopathology (p-factor) (Effect = 0.0079, BootSE = 0.0049, LLCI = 0.0004, ULCI = 0.0191), anxiety symptoms (Effect = 0.0075, BootSE = 0.0047, LLCI = 0.0001, ULCI = 0.0182), and school performance (Effect = −0.0167, BootSE = 0.0077, LLCI = −0.0327, ULCI = −0.0028), but not PE.</div></div><div><h3>Conclusions</h3><div>PRS-SZ was associated with poorer EF, which in turn mediated its associations with increased general psychopathology (p-factor) and anxiety symptoms, and reduced school performance in this community youth sample. EF may represent a hub through which PRS-SZ contributes to negative behavioral and functional outcomes.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 9-16"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the prognosis of primary and substance-associated psychoses using urine drug screens: A 5-year retrospective longitudinal study using medical records","authors":"Erich J. Aschenbrenner ,&nbsp;Andrew C. Voluse","doi":"10.1016/j.schres.2026.01.023","DOIUrl":"10.1016/j.schres.2026.01.023","url":null,"abstract":"<div><div>Substance use is frequently implicated in psychosis. However, the prognostic assumptions guiding differential treatment decisions between substance-induced and primary/affective psychoses have received inconsistent support. Substance-induced psychosis research has often been limited by aggregating substances or using diagnosis as both a grouping variable and an outcome (i.e., diagnostic conversion). The current study examined medical records for 1379 patients for 5 years following their first presentation with psychosis after January 2013 to a regional medical center. Clinically relevant outcomes were compared across groups defined by the substances detected in patients' urine at their initial presentation. Initial drug screen results predicted the initial encounter duration, the likelihood of a future presentation with psychosis and a negative drug screen, and the total hospital days associated with psychosis over 5 years, but not patients' number of psychiatric hospitalizations. Cocaine alone and cannabis combined with stimulants exhibited the courses expected of substance-induced psychosis, including quick remission, infrequent recurrence with negative drug screens, and low healthcare utilization. Amphetamines and cannabis alone exhibited improved prognoses compared to those with negative initial screens, but more chronic courses than expected of substance-induced psychosis. Depressants exhibited similar courses to those with negative initial screens. Other polysubstance combinations displayed divergent outcomes. The chronicity of psychosis associated with certain substances suggests further examination of their course with protracted abstinence, response to psychosis-focused treatments, and the potentially diverse mechanisms by which use precipitates psychosis. Additionally, the dissimilar courses observed for distinct polysubstance combinations emphasize the importance of disambiguating these groups in future research.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 57-64"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and multidimensional impact of sarcopenia in schizophrenia: Associations with oxidative stress, functioning, and symptom severity","authors":"Özgü Şişman ,&nbsp;Sinay Önen","doi":"10.1016/j.schres.2026.01.002","DOIUrl":"10.1016/j.schres.2026.01.002","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (R² = 0.10, p = .011). No significant differences were found in mean TAC, TOS, and OSI between sarcopenic and non-sarcopenic groups.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 61-70"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between reduced plasma dopamine β-hydroxylase levels and immediate memory impairment in first-episode drug-naïve schizophrenia","authors":"Ling Chan Wang ,&nbsp;An Kun Lu ,&nbsp;Zhen Hua Zhu ,&nbsp;Wen Long Hou ,&nbsp;Xuyuan Yin ,&nbsp;Qing Yang ,&nbsp;Li Juan Man ,&nbsp;Jie Chen ,&nbsp;Hong Liang Zhu ,&nbsp;Xin Yu ,&nbsp;Huiping Zhang ,&nbsp;Li Hui","doi":"10.1016/j.schres.2026.01.011","DOIUrl":"10.1016/j.schres.2026.01.011","url":null,"abstract":"<div><div>Dopamine β-hydroxylase (DBH) is an enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE). The dysregulation of these neurotransmitters is implicated in the etiology and cognitive impairments of schizophrenia. However, the relationship between DBH and cognitive impairments of schizophrenia, independent of confounding effects of medication and chronic illness, remains unclear. Thus, this case-control study aimed to investigate plasma DBH levels, cognitive performance, and their association in patients with first-episode drug-naïve schizophrenia (FDS). A total of 56 FDS patients and 56 age- and gender-matched healthy controls (HCs) were enrolled. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and plasma DBH levels were measured via sandwich enzyme-linked immunosorbent assays (ELISAs). After adjusting for covariates, plasma Log₁₀DBH levels were significantly lower in FDS patients compared to HCs (F = 9.17, <em>p</em> = 0.003). Moreover, plasma Log₁₀DBH levels showed a positive correlation with immediate memory score in patients (<em>r</em> = 0.27, <em>p</em> = 0.04). Linear regression further confirmed a significant association between Log₁₀DBH levels and immediate memory score in patients (β = 50.18, <em>t</em> = 2.82, <em>p</em> = 0.008). Additionally, FDS patients scored significantly lower than HCs on the RBANS total score and all subdomains, except visuospatial/constructional score (all, <em>p</em> &lt; 0.001). These findings suggest that reduced plasma DBH levels might be strongly associated with schizophrenia and might contribute to immediate memory impairment in FDS patients.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 94-99"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multimodal fusion analysis of structural and functional abnormalities in acute onset treatment-resistant schizophrenia","authors":"Peiyu Cao ,&nbsp;Yanlin Han ,&nbsp;Lulu Zou ,&nbsp;Shuzhan Gao ,&nbsp;Qing Xu ,&nbsp;Chaoyong Xiao ,&nbsp;Xijia Xu","doi":"10.1016/j.schres.2026.01.008","DOIUrl":"10.1016/j.schres.2026.01.008","url":null,"abstract":"<div><h3>Background</h3><div>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.</div><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 25-32"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antipsychotic use and associating factors among persons with substance-induced psychosis and first-episode psychotic disorder- A nationwide register-linkage study","authors":"Jeyaniroshan Jeyapalan ,&nbsp;Heidi Taipale ,&nbsp;Antti Tanskanen ,&nbsp;Jari Tiihonen ,&nbsp;Ellenor Mittendorfer-Rutz ,&nbsp;Solja Niemelä","doi":"10.1016/j.schres.2026.01.003","DOIUrl":"10.1016/j.schres.2026.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Antipsychotic use after first-episode psychotic disorder (FEPD) has been widely studied, but data on substance-induced psychosis (SIP) are lacking.</div></div><div><h3>Objectives</h3><div>To examine the prevalence and associated factors of antipsychotic use in individuals with incident SIP compared to a matched FEPD cohort.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 1-9"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “prevalence and multidimensional impact of sarcopenia in schizophrenia: Associations with oxidative stress, functioning, and symptom severity” [Schizophr. Res. volume 289, March 2026, pages–61-70]","authors":"Özgü Şişman,&nbsp;Sinay Önen","doi":"10.1016/j.schres.2026.01.017","DOIUrl":"10.1016/j.schres.2026.01.017","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Page 112"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Highlights","authors":"","doi":"10.1016/S0920-9964(26)00049-6","DOIUrl":"10.1016/S0920-9964(26)00049-6","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Page A1"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized double-blind inpatient study of a gluten-free diet for negative symptoms in people with schizophrenia","authors":"Deanna L. Kelly ,&nbsp;Christopher M. Lee ,&nbsp;Gopal Vyas ,&nbsp;Robert W. Buchanan ,&nbsp;Daniel J. Roche ,&nbsp;Valerie Harrington ,&nbsp;Laura M. Rowland ,&nbsp;S. Andrea Wijtenburg ,&nbsp;Bhim M. Adhikari ,&nbsp;Korrapati V. Sathyasaikumar ,&nbsp;Peter Kochunov ,&nbsp;Monica V. Talor ,&nbsp;James Waltz ,&nbsp;Fang Liu ,&nbsp;Stephanie Hare ,&nbsp;Heather A. Adams ,&nbsp;Robert Schwarcz ,&nbsp;Deepak Salem ,&nbsp;James M. Gold ,&nbsp;Sarah M. Clark ,&nbsp;William W. Eaton","doi":"10.1016/j.schres.2026.01.006","DOIUrl":"10.1016/j.schres.2026.01.006","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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+ (<em>N</em> = 39; <em>n</em> = 21 GFD and <em>n</em> = 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 kynurenine pathway metabolites. Also, we explored inflammatory markers and, in <em>n</em> = 20 participants, measured cerebral blood flow (CBF) using Arterial Spin Labeling, and neurochemistry using magnetic resonance spectroscopy.</div></div><div><h3>Outcomes</h3><div>Relative to a GCD, a GFD was associated with a modest decrease in CAINS MAP scores (<em>df</em> = 31.2.1, <em>F</em> = 2.96, <em>p</em> = 0.035); decrease in kynurenic acid (KYNA; <em>df</em> = 32, <em>F</em> = 9.51, <em>p</em> = 0.0042) and kynurenine (<em>df</em> = 32, <em>F</em> = 11.45, <em>p</em> = 0.0019); and increase in CBF and total creatine in frontal brain regions. KYNA and CAINS MAP change scores were correlated (<em>r</em> = 0.350, <em>p</em> = 0.039) while cognition was not impacted.</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 33-45"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}