Schizophrenia Bulletin最新文献

{"title":"Ketogenic Diet as Protection for Deprescribing Antipsychotics","authors":"Jann E Schlimme","doi":"10.1093/schbul/sbaf127","DOIUrl":"https://doi.org/10.1093/schbul/sbaf127","url":null,"abstract":"People with schizophrenia or schizoaffective disorder are almost always treated with continued use of antipsychotics. Tapering of antipsychotics is very often associated with a recurrence of symptoms within a year. This applies particularly to the final steps of reduction from very small doses. Ketosis seems to offer protection against psychotic relapses in these final steps. I report a case series that supports this thesis. Two effects of antipsychotics that disappear after discontinuation of the medication and can be replaced by ketosis could possibly be responsible for this: effects on the mesolimbic system against the background of insufficient GABAergic inhibition in the prefrontal cortex and mesolimbic system; effects on the microglia against the background of increased unspecific neuroinflammation.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"17 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omic Insight Into the Molecular Networks of Mitochondrial Dysfunction in the Pathogenesis of Schizophrenia.","authors":"Kefu Yu, Ruiqi Jiang, Shuxian Yang, Jiping Huo, Dabiao Zhou, Zhigang Zhao","doi":"10.1093/schbul/sbaf145","DOIUrl":"https://doi.org/10.1093/schbul/sbaf145","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Schizophrenia is a complex psychiatric disorder with potential links to mitochondrial dysfunction, but the underlying molecular mechanisms remain unclear. We aimed to investigate the relationship between genes encoding proteins involved in mitochondrial function and schizophrenia through multi-omic analyses.</p><p><strong>Study design: </strong>We analyzed blood-derived methylation, expression, and protein quantitative trait loci data integrated with schizophrenia genetic associations. We employed summary-data-based Mendelian randomization and colocalization analyses to identify potential associations. Phenome-wide association studies and molecular docking explored target druggability.</p><p><strong>Study results: </strong>We identified ACADVL, encoding very long-chain specific acyl-CoA dehydrogenase, as associated with schizophrenia across methylation, expression, and protein levels. Higher ACADVL methylation was associated with increased schizophrenia risk, while higher expression and protein levels were protective. Phenome-wide analyses showed no significant associations with other traits and molecular docking showed good binding affinity between ACADVL and bisphenol A and perfluorooctanoic acid. Drug repurposing identified cholic acid, chenodeoxycholic acid, and deoxycholic acid as potential ACADVL-targeting agents.</p><p><strong>Conclusions: </strong>Our blood-based multi-omic analyses suggest ACADVL plays a role in schizophrenia pathophysiology. ACADVL represents a promising drug target for schizophrenia. Further validation and clinical trials are needed to explore ACADVL-based treatments for schizophrenia.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gesture Impairments in Schizophrenia: Distinct Roles of Negative Symptoms and Formal Thought Disorder","authors":"Anastasia Pavlidou, Fiona Reiser, Lydia Maderthaner, Sofie von Känel, Victoria Chapellier, Alexios Malifatouratzis, Sebastian Walther","doi":"10.1093/schbul/sbaf152","DOIUrl":"https://doi.org/10.1093/schbul/sbaf152","url":null,"abstract":"Background and Hypothesis Gesture impairments are increasingly recognized as a core feature of schizophrenia, apparent across different domains and gesture categories. However, the potential differential effects of specific symptom domains on distinct types of gestures are unknown. The current study aimed to investigate whether specific domains of negative symptoms (NS) and formal thought disorder (FTD) relate to different aspects of gesture performance in patients with schizophrenia. Study Design Gesture accuracy was assessed using the well-established test of upper limb apraxia, which examines performance across 2 domains and 3 semantic categories in 87 patients with schizophrenia and 57 age- and gender-matched controls. Further, we used standardized clinical rating scales to assess NS and FTD across their different subdomains. Study Results Patients performed worse than controls in both domains and all gesture categories. Further, both NS and FTD were associated with gesture impairments, yet the associations were distinct. Negative symptoms, particularly avolition and affective flattening, as well as Objective Negative FTD, were specifically linked to reduced performance of pantomime meaningless gestures. Conversely, Objective Positive FTD was associated with a broader range of gesture deficits, impacting both imitation and pantomime domains, including intransitive and transitive gestures. Conclusions Our findings reveal that gesture impairments in schizophrenia vary across distinct symptom domains, indicating that NS and FTD contribute differently to motor and cognitive dysfunctions suggesting different underlying neural mechanisms. These insights can guide targeted interventions to address specific gesture deficits based on underlying psychopathology.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"9 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fidelity, Implementation Determinants, and Patient-Level Outcomes Following Initial Implementation of NAVIGATE in the Early Psychosis Intervention-Spreading Evidence-Based Treatment (EPI-SET) Study.","authors":"Melanie Barwick, Janet Durbin, George Foussias, Emily Panzarella, Marleine Saliba, Sandy Brooks, Elaine Stasiulis, Raluca Dubrowski, Paul Kurdyak, Sanjeev Sockalingam, Donald Addington, Augustina Ampofo, Kelly Anderson, Sarah Bromley, Monica Choi, Simone Dahrouge, Lillian Duda, Alexia Jaouich, Christopher Koegl, Carol Maxwell, Dielle Miranda, Claire de Oliveira, Alexia Polillo, Valerie Primeau, John Riley, Dayna Rossi, Eva Serhal, Jill Shakespeare, Sophie Soklaridis, Diana Urajnik, Nicole Kozloff, Aristotle Voineskos","doi":"10.1093/schbul/sbaf119","DOIUrl":"https://doi.org/10.1093/schbul/sbaf119","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>While early psychosis intervention (EPI) services are effective, care delivery is often inconsistent, particularly in recovery-oriented care. We hypothesized that facilitated implementation of NAVIGATE, an evidence-based, standardized model of coordinated specialty care, would increase fidelity to EPI standards and improve patient functioning in real-world settings.</p><p><strong>Study design: </strong>The Early Psychosis Intervention-Spreading Evidence-based Treatment (EPI-SET) study was a non-randomized effectiveness-implementation hybrid type III trial in 6 Ontario EPI programs. We used the First Episode Psychosis Services-Fidelity Scale-Revised (FEPS-FS-R) to measure fidelity to EPI standards at baseline (T0) and 12 months (T1). Scores ranged from 1 to 5, indicating poor (<3.5), fair (3.5-4), and good (≥4.0) adherence. The Heinrichs-Carpenter Quality of Life Scale (QLS) was used to determine change in functioning from baseline to 12 months (which roughly coincided with the T1 fidelity assessment). Implementation determinants were assessed using the Consolidated Framework of Implementation Research.</p><p><strong>Study results: </strong>FEPS-FS-R scores indicated good adherence for 19/29 items at T0 and 17/29 items at T1. Compared to T0, at T1, more psychosocial treatment items and fewer access and continuity items achieved fair or better adherence. Among the 100 participants who completed a baseline assessment, QLS total scores improved significantly (estimated change = 13.6, 95% CI: 9.6-17.7, P < .001) from T0 to T1. Implementation experiences varied across sites, with 4 of 6 organizations reporting overall positive experiences.</p><p><strong>Conclusions: </strong>Implementation of NAVIGATE was associated with improved fidelity to psychosocial components of care, with concomitant improvements in patient functioning. These findings can inform widespread implementation of NAVIGATE.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gα13 Overexpression in the Medial Prefrontal Cortex Disrupts Social Behavior Through the Adcyap1/cAMP/PKA/NMDAR Pathway","authors":"Rui Fan, Jianlin Pu, Jin Zhang, Minglan Yu, Tingting Wang, Xiaoqi Geng, Wei Dong, Rong Ma, Binglong Wang, Jianfei Wu, Kezhi Liu, Kenji Hashimoto, Bo Xiang","doi":"10.1093/schbul/sbaf131","DOIUrl":"https://doi.org/10.1093/schbul/sbaf131","url":null,"abstract":"Background Social withdrawal is a core symptom of schizophrenia (SCZ), yet its underlying molecular mechanisms remain unclear. Gα13 (GNA13), a G protein alpha subunit, has been implicated in SCZ susceptibility. This study investigated the role of Gα13 in social behavior by overexpressing it in the medial prefrontal cortex (mPFC) pyramidal neurons of mice. Study Design In this study, we first constructed CRE recombinase overexpressing Gα13 gene mice using CRISPR/Cas9 technology, tested the social behaviors by three-box socialization test, detected the changes of neuronal activities during social activities in mice by calcium signal fiber-optic recordings, observed the changes of dendritic spines by Golgi staining, applied RNA sequencing (RNA-Seq) to find the relevant targets, and observed whether it could reverse the abnormalities by pharmacological experiments social behavior. The electrophysiological characteristics of Gα13 overexpression were investigated using the whole-cell membrane clamp technique, followed by assessment of the severity of SCZ patients and social withdrawal using the PANSS scale and measurement of human plasma Gα13 protein levels using the ELISA technique, and the clinical correlation between the two was assessed. Study Results Gα13 overexpression (Gα13-OE) mice exhibited significant social deficits in the three-chamber test, showing reduced sociability but normal social novelty recognition. Fiber photometry recordings revealed decreased neuronal activity during social interactions, and Golgi staining showed reduced dendritic spine density in mPFC pyramidal neurons. RNA-Seq identified downregulation of Adcyap1, affecting the cAMP/PKA signaling pathway and NMDA receptor (NMDAR) function. Pharmacological activation of Adcyap1 with PACAP-38 or NMDAR with D-cycloserine rescued the social deficits and restored synaptic function. Conversely, knockdown of Gα13 in an MK-801-induced SCZ mouse model ameliorated social behavior abnormalities. Clinically, patients with SCZ exhibited elevated plasma levels of Gα13, which positively correlated with the severity of social withdrawal symptoms measured by the PANSS G16 item. Conclusions These findings suggest that overexpression of Gα13 in the mPFC impairs social behavior by disrupting neuronal function and synaptic plasticity via the Adcyap1/cAMP/PKA/NMDAR pathway. Targeting Gα13 may offer a novel therapeutic strategy for addressing social deficits in SCZ.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"190 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine Dose Reduction in Remitted Patients With Treatment-Resistant Schizophrenia: A Case Series","authors":"Mohammed A Alarabi, Akash Prasanna Kumar, Valerie Powell, Leah Burton, Sacha Agrawal, Tanner Isinger, Gary Remington, Sri Mahavir Agarwal","doi":"10.1093/schbul/sbaf139","DOIUrl":"https://doi.org/10.1093/schbul/sbaf139","url":null,"abstract":"Background There is limited evidence on the outcomes of clozapine deprescribing in remitted treatment-resistant schizophrenia (TRS) patients. We present a series of TRS patients in remission who underwent progressive reductions in their maintenance clozapine dose. Study Design This was a retrospective chart review of patients treated with clozapine from March 20, 2014 to March 20, 2024, at the Centre for Addiction and Mental Health, Toronto, Canada. We included patients who met criteria for TRS, were in remission on clozapine, and underwent progressive reduction &amp;gt; 25% in their maintenance dose. Study Results Of the 9 cases included, 4 (44.4%) maintained remission following progressive dose reductions. Two patients (22.2%) relapsed and were hospitalized, while 3 (33.3%) relapsed and required an increase in clozapine dose. Of those who relapsed, 3 had subtherapeutic clozapine levels and one had stopped clozapine before relapse. Overall dose reductions ranged from 100% (complete discontinuation with sustained remission) to 25% (with subsequent dose increase after relapse). The average rate of clozapine reduction was slow across cases, with a median of 25 mg every 12 weeks. Although not statistically significant, patients who maintained remission had slower tapering rates, ranging from 25 mg every 5 weeks to 25 mg every 2 years. Conclusions Reducing the clozapine maintenance dose in remitted TRS patients carried a substantial risk of relapse. The risk may be lower when dose reductions are guided by clozapine levels and implemented gradually over several months to years. Larger samples are needed to identify predictors of relapse in TRS patients undergoing clozapine deprescribing.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"43 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Antipsychotic Dose Reduction on Movement Disorders and Cardiometabolic Indices in Patients Remitted from a First Episode of Psychosis.","authors":"Yinzhao Liu, Iris E Sommer, Marieke J H Begemann, Shiral S Gangadin, Benjamin I Perry, Toon A W Scheurink, Nico J M van Beveren, Pieter Roberto Bakker, Sanne Koops","doi":"10.1093/schbul/sbaf116","DOIUrl":"https://doi.org/10.1093/schbul/sbaf116","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The extent to which tapering antipsychotic (AP) attenuates AP-related movement disorders and cardiometabolic dysfunction remains unclear. We aim to investigate the long-term effects of AP-dose reduction on these adverse effects in patients remitted from a first episode of psychosis (FEP).</p><p><strong>Study methods: </strong>We included 293 FEP participants from the HAMLETT trial. Movement disorders were assessed using the St. Hans Rating Scale (SHRS) and Barnes Akathisia Rating Scale. Cardiometabolic indices included body mass index (BMI), waist circumference, blood pressure (BP), glucose, triglycerides, and cholesterol. Linear mixed-effects models assessed longitudinal relationships between AP-dose reduction, movement disorders and cardiometabolic indices.</p><p><strong>Study results: </strong>Over an average 29-month follow-up (SD = 19), a 1 mg olanzapine equivalent dose reduction from baseline was associated with a 0.013-point decrease in Parkinsonism (95% CI, -0.019, -0.006), a potential 0.003-point decrease in tardive dyskinesia (95% CI, -0.006, -0.000) on SHRS (range 0-6), and decreases of 0.037 (0.15%) kg/m2 in BMI (95% CI, -0.059, -0.015), 0.153 (0.17%) cm in waist circumference (95% CI, -0.265, -0.037), 0.023 (0.47%) mmol/L in total cholesterol (95% CI, -0.039, -0.007), 0.018 (0.60%) mmol/L in low-density lipoprotein cholesterol (95% CI, -0.032, -0.003), and 0.021 (0.58%) mmol/L in nonhigh-density lipoprotein cholesterol (95% CI, -0.037, -0.005). We found no evidence for an association with tardive dystonia, akathisia, BP, glucose, or triglycerides.</p><p><strong>Conclusions: </strong>AP-dose reduction modestly benefits AP-related Parkinsonism, weight gain, cholesterol levels and potentially tardive dyskinesia in patients after FEP over time. These benefits should be carefully weighed against the risks of relapse and suicide.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eye Movement Abnormalities During the Gaze Perception Task in Individuals With Clinical High Risk for Psychosis: A Discriminant Analysis With Hidden Markov Models","authors":"Harry Kam Hung Tsui, Yingqi Liao, Janet Hui-wen Hsiao, Yi Nam Suen, Eric Wai Ching Yan, Lap-Tak Poon, Man Wah Siu, Christy Lai Ming Hui, Wing Chung Chang, Edwin Ho Ming Lee, Eric Yu Hai Chen, Sherry Kit Wa Chan","doi":"10.1093/schbul/sbaf105","DOIUrl":"https://doi.org/10.1093/schbul/sbaf105","url":null,"abstract":"Objectives Social cognitive impairments were well-documented in schizophrenia and individuals with clinical high risk for psychosis (CHR). While eye movement abnormalities during gaze perception in schizophrenia have been suggested, such understanding in individuals with CHR is limited. Design, Settings and Participants This study recruited 36 CHR individuals and 50 healthy controls (HC) to perform a gaze perception task with eye-tracking techniques analyzed with hidden Markov models for predictability and pattern recognition. Eye movement variables and behavioral responses, self-referential gaze perception (SRGP) rates, were compared between groups and examined with discriminant analyses. Associations between eye movements and SRGP rates with multiple symptom dimensions and social functioning were examined. Results Results indicated that CHR group displayed nose-focused (vs eye-focused) and erratic eye movement patterns compared to HC. The combination of behavioral and eye movement variables exhibited a discriminatory ability of 0.893 area under the curve (AUC) in classifying CHR and HC, significantly outperforming models using either SRGP rates (AUC = 0.824) or eye movement variables (AUC = 0.781) alone. The combined model achieved high sensitivity (0.861) and specificity (0.820), with eyes-nose scale, fixation duration, and ambiguous SRGP rate emerging as the most discriminative features. Self-referential gaze perception rates were primarily associated with schizotypy and social anxiety, while eye movement patterns were mainly associated with delusional ideations and social functioning. Conclusions and Relevance This study comprehensively examined eye movement patterns during gaze perception in CHR and their associations with clinical manifestations, suggesting the potential of visual attention patterns as both diagnostic biomarkers and therapeutic targets in the CHR population.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"35 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Passive Sensing to Predict Psychosis Relapse: An In-Depth Qualitative Study Exploring Perspectives of People With Psychosis.","authors":"Emily Eisner, Hannah Ball, John Ainsworth, Matteo Cella, Natalie Chalmers, Sybil Clifford, Richard J Drake, Daniel Elton, Sophie Faulkner, Kathryn Greenwood, Andrew Gumley, Gillian Haddock, Kimberley M Kendall, Alex Kenny, Tor-Ivar Krogsæter, Jane Lees, Shôn Lewis, Laura Maclean, Kathryn O'Hare, Alie Phiri, Cara Richardson, Matthias Schwannauer, Rebecca Turner, Annabel Walsh, James Walters, Til Wykes, Uzma Zahid, Sandra Bucci","doi":"10.1093/schbul/sbaf126","DOIUrl":"https://doi.org/10.1093/schbul/sbaf126","url":null,"abstract":"<p><strong>Background: </strong>Relapses result in negative consequences for individuals with psychosis and considerable health service costs. Digital remote monitoring (DRM) systems incorporating \"passive sensing\" (sensor data gathered via smartphones/wearables) may be a low-burden method for identifying relapses early, enabling prompt intervention and potentially averting the consequences of full relapse.</p><p><strong>Objective: </strong>This study examined detailed views from people with psychosis about using passive sensing in this context.</p><p><strong>Study design: </strong>Qualitative interviews, analyzed using reflexive thematic analysis. Setting: Secondary care mental health services across the United Kingdom. An advisory group with relevant lived experience was involved throughout, from developing the topic guide to analysis. Participants: Clinician confirmed diagnosis of schizophrenia-spectrum psychosis (n = 58).</p><p><strong>Study results: </strong>Four overarching themes were developed. Theme 1 outlined participants' polarized feelings about passive sensing, highlighting specific challenges relating to privacy, especially regarding location data. Theme 2 examined participants' fears that clinicians might judge their movements or routines, creating a sense of pressure to modify their actions and undermining their autonomy. Theme 3 described potential solutions: offering users choice about what data are shared, when, and with whom. Theme 4 outlined specific benefits that participants valued, including intended functions of passive sensing within DRM (ease of use, early identification of relapse, and relevance of sleep monitoring) and novel uses.</p><p><strong>Conclusions: </strong>Our findings underline the importance of fully informed consent, choice, and autonomy. Given the potential privacy impacts, individuals are unlikely to engage with passive sensing unless they perceive clear personal benefits. Prospective DRM users need clear, accessible information about passive data collection and its relevant costs and benefits.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Gut Microbial Signatures and Diminished Anti-Inflammatory Effect of Short-Chain Fatty Acids in Schizophrenia With Immune Activation","authors":"Xiaoyan He, Yuan Gao, Yudan Zhang, Zai Yang, Chuyao Wang, Qingyan Ma, Pu Lei, Lu Yu, Yajuan Fan, Ruina Liu, Wei Wang, Jianbo Zhang, Xiancang Ma, Feng Zhu","doi":"10.1093/schbul/sbaf110","DOIUrl":"https://doi.org/10.1093/schbul/sbaf110","url":null,"abstract":"Background and Hypothesis A subset of patients with schizophrenia (SCZ) exhibit subclinical immune activation. However, the gut microbial features of this subgroup and their interplay with the immune function remain poorly understood. This study aimed to identify the gut microbiome signature of immune-activated SCZ and elucidate the role of short-chain fatty acids (SCFAs) in the gut-immune crosstalk. Study Design In this study, 297 patients with SCZ and 301 healthy controls (HCs) were assessed for 4 serum immune mediators. Immune-activated subgroups were classified based on these biomarkers. Fecal metagenomic sequencing, SCFA metabolomics, and in vitro peripheral blood mononuclear cells (PBMCs) stimulation experiments were performed to analyze the microbial composition, SCFA levels, and immune responses. Study Results We found that 46.5% of the patients with SCZ exhibited elevated immune activation biomarker levels, which displayed unique bacterial signatures. Microbiome-based machine learning classifiers demonstrated robustness in SCZ and immune activation classification. Notably, microbial species abundance, functional metagenomics, and SCFA levels have confirmed an elevated capacity for SCFA production in patients with immune activation. Furthermore, in vitro PBMC stimulation experiments revealed a diminished anti-inflammatory effect of SCFAs in immune-activated patients when exposed to lipopolysaccharide-induced inflammation. Conclusions This study delineates the gut microbiome and SCFA metabolic profiles of immune-activated SCZ patients, revealing an association between gut microbiota dysbiosis, enhanced SCFA production capacity, and diminished anti-inflammatory effect of SCFA. These findings provide new insights into the underlying mechanisms and potential targeted treatments for SCZ patients with immune activation.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"9 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}