Schizophrenia Research最新文献

{"title":"Improving systems & communities of psychosis care: Proceedings from the 2024 Mass-STEP Conference","authors":"Iqra Imam ,&nbsp;Kelsey A. Johnson ,&nbsp;Ananya Saluja ,&nbsp;Raquelle I. Mesholam-Gately ,&nbsp;Margaret E. Guyer ,&nbsp;Dost Ongur ,&nbsp;Matcheri S. Keshavan","doi":"10.1016/j.schres.2025.12.004","DOIUrl":"10.1016/j.schres.2025.12.004","url":null,"abstract":"<div><div>A 2024 conference titled “<em>Early Intervention in Psychosis: Systems &amp; Communities of Care</em>” 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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"288 ","pages":"Pages 66-68"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878971","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":"Neighborhood environmental deprivation predicts the generalized neurocognitive deficit in schizophrenia","authors":"Luyu Zhang,&nbsp;Zhixin Zhang,&nbsp;Gregory P. Strauss","doi":"10.1016/j.schres.2025.12.006","DOIUrl":"10.1016/j.schres.2025.12.006","url":null,"abstract":"<div><h3>Background</h3><div>The generalized neurocognitive deficit is a core feature of schizophrenia (SZ). However, no current treatments have demonstrated satisfactory efficacy in remediating cognitive impairment in this population. This lack of treatment progress might be due in part to the failure to consider broader environmental factors and social determinants of health. The current paper explored the contributing role of these factors to the generalized neurocognitive deficit in SZ.</div></div><div><h3>Methods</h3><div>Participants included 114 outpatients with SZ and 117 matched healthy controls (CN) who completed a cross-sectional study. Cognitive impairment was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Environmental deprivation was measured by Area Deprivation Index (ADI). Rurality was measured by the rural urban continuum code (RUCC). A linear regression model was fitted to predict MCCB total score with ADI, RUCC, and the interaction between ADI and RUCC as predictors.</div></div><div><h3>Results</h3><div>The overall model was significant, <em>F</em> = 8.06, <em>p</em> &lt; .001, <em>R</em>^<em>2</em> = 0.14. The effect of ADI score was also significant, <em>β</em> = −0.36, <em>t</em> = −2.30, <em>p</em> &lt; .05; while the effect of RUCC, <em>β</em> = 0.06, <em>t</em> = 0.34, <em>p</em> = .73, and the interaction between ADI and RUCC, <em>β</em> = −0.001, <em>t</em> = 0.27, <em>p</em> = .99, were nonsignificant.</div></div><div><h3>Conclusions</h3><div>Neighborhood-level environmental deprivation predicted cognitive impairment in SZ. This highlights the need to incorporate environment-focused interventions when treating cognitive impairment in SZ.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"288 ","pages":"Pages 18-25"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792168","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":"S100A8 dysregulation as a neuroimmune nexus: Bridging childhood inflammatory infections to adult schizophrenia-like behaviors via the ELNI model","authors":"Chen Tengfei ,&nbsp;Wang Shiyu ,&nbsp;Sheng Longyu ,&nbsp;Cheng Lei ,&nbsp;Fang Ni ,&nbsp;Wang Yaoyu ,&nbsp;Zhang Jianing ,&nbsp;Liu Qing ,&nbsp;Liu Kang ,&nbsp;Li Jie ,&nbsp;Badrul Hisham Bin Yahaya ,&nbsp;Juntang Lin ,&nbsp;Wenqiang Li","doi":"10.1016/j.schres.2025.12.016","DOIUrl":"10.1016/j.schres.2025.12.016","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>We analyzed gene expression datasets from blood and brain of SCZ patients and pediatric infections (GEO accessions: <span><span>GSE53987</span><svg><path></path></svg></span>, <span><span>GSE73464</span><svg><path></path></svg></span>, <span><span>GSE38484</span><svg><path></path></svg></span>) 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"288 ","pages":"Pages 47-56"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828208","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":"Is it the end of the clozapine world as we know it? Perspectives on social implications of REMS elimination","authors":"Melissa Uehling ,&nbsp;Deon Hamm ,&nbsp;David Goldsmith ,&nbsp;Julia Brown","doi":"10.1016/j.schres.2025.12.013","DOIUrl":"10.1016/j.schres.2025.12.013","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"288 ","pages":"Pages 57-58"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828272","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":"Pharmacokinetic correlates of clinical response in a retrospective naturalistic cohort of patients treated with long-acting injectable antipsychotics","authors":"Nazar Kuzo ,&nbsp;Davide Gaspari ,&nbsp;Fabio Carpi ,&nbsp;Christoph Hiemke ,&nbsp;Michael Paulzen ,&nbsp;Andreas Conca ,&nbsp;Georgios Schoretsanitis","doi":"10.1016/j.schres.2025.12.012","DOIUrl":"10.1016/j.schres.2025.12.012","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the pharmacokinetic correlates of clinical response to long acting injectable (LAI) antipsychotics in a naturalistic outpatient sample.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>In a total of 158 LAI-treated outpatients, responders (42.4 %) were significantly younger (50.5 vs. 55.6 years, <em>p</em> = 0.002) and more often treated with monotherapy (64.2 % vs. 44.0 %, <em>p</em> = 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 (<em>p</em> = 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, <em>p</em> = 0.02) and with levels within the TRR (aOR: 23.01, 95 % CI: 1.28–414.48, <em>p</em> = 0.03) had higher probability of treatment response compared to those with supratherapeutic concentrations, while these estimates were limited by the small group size (<em>n</em> = 9). Younger age (aOR: 0.97, 95 % CI: 0.94–0.99, <em>p</em> = 0.04) and LAI monotherapy (aOR = 3.77, 95 % C<em>I</em> = 2.19–6.51, <em>p</em> = 0.001) were associated with better treatment response.</div></div><div><h3>Conclusions</h3><div>Assessing antipsychotic concentrations combined with clinical characteristics such as LAI monotherapy and age may be useful for guiding pharmacotherapy with LAIs.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"288 ","pages":"Pages 38-46"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828238","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":"Predictions of different elements of everyday functional outcomes in bipolar disorder and schizophrenia: Cognition, social cognition, clinical symptoms, and mood states as predictors","authors":"Megan A. Neff ,&nbsp;Katherine V. Raffensperger ,&nbsp;Raeanne C. Moore ,&nbsp;Colin A. Depp ,&nbsp;Robert A. Ackerman ,&nbsp;Amy E. Pinkham ,&nbsp;Philip D. Harvey","doi":"10.1016/j.schres.2025.12.018","DOIUrl":"10.1016/j.schres.2025.12.018","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>Participants with bipolar disorder (BD; <em>n</em> = 114) and SZ (SZ; <em>n</em> = 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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Implications</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"288 ","pages":"Pages 77-85"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884701","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":"Does insight improve during the course of psychosis?","authors":"Pegah Seif ,&nbsp;Elisabetta Claudia del Re ,&nbsp;Carol A. Tamminga ,&nbsp;Godfrey D. Pearlson ,&nbsp;Brett A. Clementz ,&nbsp;Jennifer McDowell ,&nbsp;Elena I. Ivleva ,&nbsp;Kareem Hamada ,&nbsp;Scot Hill ,&nbsp;Sarah K. Keedy ,&nbsp;Elliot S. Gershon ,&nbsp;Matcheri Keshavan","doi":"10.1016/j.schres.2025.11.005","DOIUrl":"10.1016/j.schres.2025.11.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Insight, awareness of illness, is often impaired in psychotic disorders and relates to symptom severity and cognition, but its association with time since first diagnosis is unclear. We examined insight, cognition, and time since first diagnosis in a large multi-diagnostic sample.</div></div><div><h3>Methods</h3><div>We studied patients with schizophrenia (SZ, <em>n</em> = 957), schizoaffective disorder (SAD, <em>n</em> = 723) and bipolar I disorder with psychotic features (BP, <em>n</em> = 691). Cognitive function was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS) battery. Insight was measured using item G12 from the Positive and Negative Syndrome Scale (PANSS), where higher scores indicate poorer insight.</div></div><div><h3>Results</h3><div>Insight differed by diagnosis (<em>p</em> &lt; .001), poorest in SZ vs SAD and BP. Within SZ, first-year cases had higher PANSS-G12 than those ≥3 years from first diagnosis (<em>p</em> &lt; .01). Hierarchical regressions showed diagnosis and symptom severity explained most variance in insight; cognition added only a small increment. In SZ, insight was modestly inversely related to time since first diagnosis (ρ = −0.124, <em>p</em> = .001) and weakly to cognition (ρ = −0.084, <em>p</em> = .029). Poorer insight correlated with more severe negative (ρ = 0.259, <em>p</em> &lt; .001) and positive symptoms (ρ = 0.347, p &lt; .001). No associations with time since diagnosis or cognition were seen in SAD or BP.</div></div><div><h3>Conclusion</h3><div>In SZ, insight showed a statistically significant but very small cross-sectional association with longer time since first diagnosis (better insight with longer duration), with the largest deficit in the first year. Early, diagnosis-tailored psychoeducation and metacognition-focused supports may help support gains in insight and engagement.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"287 ","pages":"Pages 63-70"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145570534","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":"Shared genetic effects among schizophrenia, substance use disorder, and hippocampal volume in a multiplex extended pedigree sample","authors":"Christie W. Musket ,&nbsp;Petra E. Rupert ,&nbsp;Susan S. Kuo ,&nbsp;David R. Roalf ,&nbsp;Konasale M. Prasad ,&nbsp;Joel Wood ,&nbsp;Ruben C. Gur ,&nbsp;Laura A. Almasy ,&nbsp;Raquel E. Gur ,&nbsp;Vishwajit L. Nimgaonkar ,&nbsp;Michael F. Pogue-Geile","doi":"10.1016/j.schres.2025.11.014","DOIUrl":"10.1016/j.schres.2025.11.014","url":null,"abstract":"<div><h3>Background</h3><div>Many individuals with schizophrenia have comorbid substance use disorders (SUD) and yet the reasons for this comorbidity are largely unknown. The current study examined if shared genetic effects jointly increase risk for both schizophrenia and SUD and if shared genetic effects on brain structure phenotypes mediate this relationship.</div></div><div><h3>Methods</h3><div>Data were collected using a multiplex extended pedigree design ascertained through schizophrenia probands (total sample <em>N</em> = 1306, with <em>N</em> = 789 relatives and <em>N</em> = 517 unrelated controls) to investigate the degree to which genetic effects are shared among schizophrenia, four SUDs, and structural MRI measures of surface area, cortical thickness, and subcortical volumes. Given that all predictions were directional (e.g., that schizophrenia would be positively genetically correlated with substance use), one-tailed <em>t</em>-tests were used with false discovery rate (FDR) correction when appropriate.</div></div><div><h3>Results</h3><div>As predicted, schizophrenia was significantly genetically correlated with any SUD excluding nicotine (R_g = 0.27, <em>p</em> = 0.033), alcohol use disorder (R_g = 0.35, <em>p</em> = 0.006), and cannabis use disorder (R_g = 0.24, <em>p</em> = 0.011). Next, using a subset of the sample that underwent structural magnetic resonance imaging (<em>N</em> = 506), brain structure phenotypes genetically correlated with both schizophrenia and SUD were identified. Only hippocampal volume was significantly genetically correlated with both schizophrenia (R_g = −0.53, <em>p</em> = 0.001) and any SUD (R_g = −0.57, <em>p</em> = 0.043). Furthermore, genetic effects shared between schizophrenia and SUD were significantly statistically mediated by the genetic effects on hippocampal volume.</div></div><div><h3>Conclusions</h3><div>These findings indicate that shared genetic effects may partially explain the observed comorbidity between schizophrenia and SUD and may suggest a unique role of the hippocampus in the pathophysiology of both schizophrenia and SUD.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"287 ","pages":"Pages 138-146"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736643","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":"Effects of disease duration and antipsychotics on brain age in schizophrenia","authors":"Alejandro Roig-Herrero ,&nbsp;Luis M. San-José-Revuelta ,&nbsp;Rafael Navarro-González ,&nbsp;Rodrigo de Luis-García ,&nbsp;Vicente Molina","doi":"10.1016/j.schres.2025.11.008","DOIUrl":"10.1016/j.schres.2025.11.008","url":null,"abstract":"<div><div>Accelerated brain aging has been consistently reported in patients with schizophrenia. Over the past decade, these findings have been replicated using the Brain Age paradigm, which applies machine learning techniques to estimate brain age from neuroimaging data. This approach yields a single index, the Brain Age Gap, defined as the difference between predicted and chronological age. Nevertheless, both the progressive nature of this phenomenon and the potential role of antipsychotic medication remain unclear.</div><div>To investigate its progression, we compared the Brain Age Gap between individuals experiencing a first episode of psychosis and healthy controls using ANCOVA, adjusting for age, sex, body mass index, and estimated total intracranial volume. To enhance the robustness of our findings, we employed two distinct models: a transformer-inspired model based on harmonized volumetric brain features extracted with FastSurfer, and a previously trained deep learning model. To assess the potential effect of medication, we further compared bipolar patients who received antipsychotic treatment with those who did not. Mann-Whitney <em>U</em> test consistently showed that medicated bipolar patients did not exhibit a significantly larger Brain Age Gap.</div><div>Both models converge on the conclusion that accelerated brain aging is unlikely to be explained by antipsychotic medication alone. Longitudinal studies are therefore required to clarify the temporal dynamics of brain aging in schizophrenia.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"287 ","pages":"Pages 82-90"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582420","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":"Perturbed sensory memory associated with schizotypy symptom load","authors":"Wendy A. Torrens,&nbsp;Jenna N. Pablo,&nbsp;Marian E. Berryhill,&nbsp;Sarah M. Haigh","doi":"10.1016/j.schres.2025.12.001","DOIUrl":"10.1016/j.schres.2025.12.001","url":null,"abstract":"<div><div>Impaired auditory event-related potential (ERP) components, including the N100 and MMN, are linked to sensory signatures of schizophrenia. <em>Nonclinical</em> individuals with schizophrenia-like traits (schizotypy) provide an attractive model for investigating these ERP biomarkers, as the individuals exhibit similar traits without clinical confounds (e.g., medications). The driving theoretical framework is that there is a continuum of traits that extends from the nonclinical population to patients diagnosed with schizophrenia spectrum disorders (SSD). Here, we tested the prediction that <em>nonclinical</em> participants high in schizotypy traits would also exhibit impaired N100 and MMN responses, reflecting impairment in early auditory processing, and/or in predicting sensory inputs. We used a simple odd-ball pitch-deviant paradigm and compared ERP amplitudes across a sample of healthy participants who completed the Schizophrenia Personality Questionnaire — Brief Revised (SPQ-BR). Participants with high total scores (high schizotypy; N = 25) were compared to middle-scoring scorers (controls; N = 32). We then investigated more nuanced relationships between ERP components and factors of the SPQ-BR (<em>cognitive-perceptual</em>, <em>interpersonal</em>, <em>disorganized</em>). High schizotypy exhibited prolonged MMN latencies but intact amplitudes—a pattern also observed in those with elevated negative symptoms. However, attenuated deviant N100 amplitudes were associated with higher <em>disorganized</em> factor scores, whereas standard and MMN amplitudes were not. Importantly, these data suggest that early deviance detection and predictive sensory memory mechanisms are differentially perturbed with schizotypy symptom load. Further research into schizotypy traits is required to validate the population for SSD risk. In conclusion, auditory impairments can be identified in <em>nonclinical</em> schizotypy and leveraged to understand disorder-related processes.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"287 ","pages":"Pages 129-137"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725778","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}