Babet N. Wezenberg , Merel Koster , Guido van Wingen , Lieuwe de Haan , Marieke van der Pluijm
{"title":"Association between sleep disturbances and gray matter volume in individuals at clinical high-risk for psychosis and healthy controls: A longitudinal MRI study (NAPLS-3)","authors":"Babet N. Wezenberg , Merel Koster , Guido van Wingen , Lieuwe de Haan , Marieke van der Pluijm","doi":"10.1016/j.schres.2025.09.010","DOIUrl":"10.1016/j.schres.2025.09.010","url":null,"abstract":"<div><h3>Objective</h3><div>Sleep disturbances and brain alterations are common in psychotic disorders and individuals at clinical high risk for psychosis (CHR-P). It remains unclear whether gray matter volume changes are inherent to psychosis or partly driven by sleep disturbances. This study investigated whether sleep disturbances contribute to progressive structural brain changes.</div></div><div><h3>Methods</h3><div>Data were obtained from the North American Prodrome Longitudinal Study (NAPLS-3), including 507 CHR-P individuals (mean age 19; 56.0 % male) and 81 healthy controls (HC) (mean age 19; 49.4 % male), assessed with the Pittsburgh Sleep Quality Index (PSQI) and 3 T structural MRI at baseline and prospectively for 8 months. Cross-sectional associations between sleep and gray matter volume were assessed with whole-brain voxel-based morphometry analysis. Longitudinal associations between persistent sleep disturbances and thalamus, hippocampus, and cerebellum volume were examined using linear mixed models.</div></div><div><h3>Results</h3><div>Sleep disturbances were highly prevalent in CHR-P (mean PSQI = 7.45) and more common than in HC (<em>p</em> < .001). No significant cross-sectional or longitudinal associations were observed between sleep disturbances and gray matter volume in CHR-P nor HC. Exploratory analyses showed that higher PSQI scores were associated with increased odds of conversion to psychosis (OR = 1.059, <em>p</em> = .040).</div></div><div><h3>Conclusions</h3><div>Our findings indicate no association between sleep disturbances and gray matter volume in CHR-P individuals or HC. This negative result suggests that sleep problems, though prevalent and predictive of psychosis risk, likely act through mechanisms other than structural brain changes, underscoring their value as accessible targets for early intervention.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 105-113"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081533","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}
Ana T. Flores , Concepción Barrio , Lan Yu , Philip D. Harvey , David L. Penn , Shaun M. Eack , Amy Pinkham
{"title":"Psychometric validation of social cognition measures in U.S. Hispanic individuals with schizophrenia","authors":"Ana T. Flores , Concepción Barrio , Lan Yu , Philip D. Harvey , David L. Penn , Shaun M. Eack , Amy Pinkham","doi":"10.1016/j.schres.2025.08.012","DOIUrl":"10.1016/j.schres.2025.08.012","url":null,"abstract":"<div><div>Little is known about cross-ethnic differences in the measurement of social cognition in minoritized groups like Hispanics, who account for a significant portion of the U.S population, potentially leading to culturally incongruent interventions. Using data from the Social Cognition Psychometric Evaluation (SCOPE), the current study conducted a cross-ethnic psychometric assessment of four social cognition measures in Hispanics diagnosed with schizophrenia (n = 73) and a non-Hispanic white group (n = 115). Tasks included Bell Lysaker Emotion Recognition Task (BLERT), Penn Emotion Recognition Task (ER-40), The Awareness of Social Inference Test (TASIT) and the Hinting Task. Tasks were evaluated on test-retest reliability, utility as a repeated measure, internal consistency, sensitivity to group differences, and relationship to functional outcomes. Mean differences between ethnic groups were also analyzed. Psychometric properties were largely adequate and comparable across ethnic groups. Mean differences on emotion recognition tasks were not significantly different between ethnic groups. However, Hispanics scored significantly lower on TASIT and the Hinting Task (assessments of theory of mind), potentially indicative of the influence of racial or cultural factors in these measures. Criterion validity also varied between groups. Although there were robust associations with functional capacity and social skills in the Hispanic group, none of the social-cognitive tasks predicted real-world functional outcomes in this group. These findings suggest that caution should be exercised when using social cognition measures to assess Hispanics and making subsequent clinical decisions.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 95-104"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061144","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}
Wenjin Liu , Katherine B. Carnelley , Katherine Newman-Taylor
{"title":"How does attachment affect help-seeking in people with paranoia and psychosis? The role of emotion regulation, self-stigma, and perceived support","authors":"Wenjin Liu , Katherine B. Carnelley , Katherine Newman-Taylor","doi":"10.1016/j.schres.2025.08.017","DOIUrl":"10.1016/j.schres.2025.08.017","url":null,"abstract":"<div><div>Longer duration of untreated psychosis causes significant human and healthcare costs. Attachment avoidance and anxiety contribute to delays in help-seeking and help-acceptance in individuals with both non-clinical and clinical paranoia, though underlying mechanisms remain unclear. The aim of the study was to examine how attachment affects help-seeking and help-acceptance in people with paranoia. We recruited a non-clinical sample with paranoia (<em>N</em> = 501) and a clinical psychosis sample (<em>N</em> = 120), and found that attachment avoidance predicted reduced help-seeking and help-acceptance intentions in both groups, while attachment anxiety predicted lower social help-seeking in the clinical group. Emotion regulation did not mediate associations between attachment and help-seeking/acceptance. Self-stigma regarding help-seeking and mental illness mediated these associations in both groups, while perceived availability of help mediated the link between avoidance and help-seeking/acceptance in the non-clinical group. This is the first study to show that self-stigma and perceived help availability delay help-seeking in paranoia. Further research should investigate causal effects of attachment on self-stigma and perceived support, and so help-seeking.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 75-86"},"PeriodicalIF":3.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046579","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}
Mojtaba Oraki Kohshour , Teresa K. Barth , Chiara Huber , Andreas Klingl , Jennifer Grünert , Urs Heilbronner , Monika Budde , Monika Rübekeil , Anton Eberharter , Thorsten Müller , Moritz J. Rossner , Andrea Schmitt , Peter Falkai , Florian J. Raabe , Sergi Papiol , Axel Imhof , Thomas G. Schulze
{"title":"Comparing the proteome profiling of plasma-derived extracellular vesicles in individuals with schizophrenia and healthy controls: a pilot study","authors":"Mojtaba Oraki Kohshour , Teresa K. Barth , Chiara Huber , Andreas Klingl , Jennifer Grünert , Urs Heilbronner , Monika Budde , Monika Rübekeil , Anton Eberharter , Thorsten Müller , Moritz J. Rossner , Andrea Schmitt , Peter Falkai , Florian J. Raabe , Sergi Papiol , Axel Imhof , Thomas G. Schulze","doi":"10.1016/j.schres.2025.09.008","DOIUrl":"10.1016/j.schres.2025.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Studying extracellular vesicles (EVs)—tiny intercellular communicators with a diverse molecular cargo—may provide insight into the poorly understood neuropathology and pathophysiology of schizophrenia (SCZ). Here, we focused on the protein profile of plasma-derived EVs with the aim to detect differences between individuals with SCZ and healthy controls (HCs).</div></div><div><h3>Methods</h3><div>EVs were isolated from blood plasma of 73 individuals with SCZ and 77 HCs and evaluated by nanoparticle tracking analysis, electron microscopy, and Western blot analysis. EV proteins were identified by liquid chromatography coupled with mass spectrometry. Proteomic data were analyzed using logistic regression analyses.</div></div><div><h3>Results</h3><div>A total of 1659 proteins were identified, and analyses were performed with the 1021 proteins with quantitative data available for more than 50 % of the participants in each group (SCZ and HC). Comparing these proteins between the two groups showed no significant differences. An enrichment analysis based on the proteins with a noncorrected significant <em>p</em> value revealed a significant enrichment of pathways connected to complement system. Although comparison of complement components between the two groups did not show significant differences, but it demonstrated that antipsychotics and duration of illness may affect EV protein levels.</div></div><div><h3>Conclusion</h3><div>Overall, even as our findings highlight the importance of medication use and duration of illness on EV protein levels, they suggest that the complement system may be involved in the etiopathology of SCZ. Although, the results of this pilot study need to be replicated in larger research, they may help elucidate the mechanisms involved in the pathophysiology of SCZ.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 87-94"},"PeriodicalIF":3.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046580","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":"Disproportionality signal for myopia associated with aripiprazole: Analysis of the FAERS database and review of the literature","authors":"Connor Frey","doi":"10.1016/j.schres.2025.09.002","DOIUrl":"10.1016/j.schres.2025.09.002","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 73-74"},"PeriodicalIF":3.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018462","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}
Jasmine Shell, Joseph P. McEvoy, William V. McCall, Brian J. Miller
{"title":"Insomnia and substance use in psychotic disorders","authors":"Jasmine Shell, Joseph P. McEvoy, William V. McCall, Brian J. Miller","doi":"10.1016/j.schres.2025.09.006","DOIUrl":"10.1016/j.schres.2025.09.006","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 70-72"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018461","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":"Thalamic hyperperfusion in early schizophrenia: Associations with cognitive deficits and negative symptoms","authors":"Ivona Orlović , Ines Šiško Markoš , Ivan Blažeković , Vjekoslav Peitl , Vivian Andrea Badžim , Tomislav Jukić , Dalibor Karlović","doi":"10.1016/j.schres.2025.08.014","DOIUrl":"10.1016/j.schres.2025.08.014","url":null,"abstract":"<div><h3>Objective</h3><div>Thalamic abnormalities have been associated with clinical and cognitive symptoms of schizophrenia, yet their role in the early stages of the disorder remain unclear. This study aimed to examine and compare thalamic perfusion differences between first-episode schizophrenia (FES) and early-course schizophrenia (ECS), along with their associations with cognitive performance and symptom severity.</div></div><div><h3>Methods</h3><div>This study included 100 unmedicated schizophrenia patients aged 19–30: 50 FES and 50 ECS (<5 years, ≥2 episodes). Symptom severity was assessed with PANSS, and cognitive function was evaluated using the 5-KOG battery. All participants underwent brain SPECT and thalamic perfusion was analyzed using MIMneuro® software with whole-brain normalization and <em>Z</em>-score extraction. Group comparisons were performed using Chi-square tests, and associations between thalamic perfusion, cognition, and symptom severity were assessed using Spearman's rank-order correlations.</div></div><div><h3>Results</h3><div>Compared to FES patients, those with ECS showed significantly higher thalamic perfusion (<em>P</em> = 0.032). In the FES group, global thalamic hyperperfusion was negatively correlated with verbal fluency (ρ = −0.374, <em>P</em> = 0.007), while in the ECS group, right thalamic perfusion was positively correlated with negative symptom severity (ρ = 0.373, <em>P</em> = 0.008).</div></div><div><h3>Conclusion</h3><div>Thalamic hyperperfusion, especially in the right hemisphere, may reflect early cognitive and clinical changes in schizophrenia. Associations with negative symptoms and verbal fluency highlight its potential as a functional biomarker. These findings support the value of early-stage imaging and warrant further longitudinal research.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 60-69"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010750","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}
Henriette T. Horsdal , Anja S. Jensen , Sussie Antonsen , Marianne G. Pedersen , Betina B. Trabjerg , Wesley K. Thompson , Chun C. Fan , Clive E. Sabel , Esben Agerbo , Carsten B. Pedersen , Roger T. Webb
{"title":"Examining relationships between the Danish Composite Deprivation Index and risk of developing schizophrenia: A national multilevel analysis","authors":"Henriette T. Horsdal , Anja S. Jensen , Sussie Antonsen , Marianne G. Pedersen , Betina B. Trabjerg , Wesley K. Thompson , Chun C. Fan , Clive E. Sabel , Esben Agerbo , Carsten B. Pedersen , Roger T. Webb","doi":"10.1016/j.schres.2025.09.001","DOIUrl":"10.1016/j.schres.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Few population-based multilevel analyses examining individual- and neighborhood-level risk factors for schizophrenia have been conducted.</div></div><div><h3>Methods</h3><div>A study cohort of all persons born in Denmark from 1990 to 1999 was followed for diagnosis with schizophrenia. Follow-up was initiated at 10th birthday and terminated at death, emigration, incident diagnosis, or 31st December 2018, whichever came first. A Danish Composite Deprivation Index was derived using 10-year weighted average neighborhood-level indicators in 1990–1999 categorized into five domains: Income; Employment; Education, Skills & Training; Health & Disability; and Crime. By fitting multilevel log-linear Poisson regression models, neighborhood-level deprivation indicators were examined with and without adjustment for individual-level covariates.</div></div><div><h3>Results</h3><div>Four neighborhood-level deprivation domains, Employment, Education, Skills & Training, Health & Disability, and Crime, as well as the Danish Composite Deprivation Index (adjusted IRR 1.14; 95 % credibility interval 1.10–1.17), were associated with elevated risk independent of individual-level deprivation measures. The specific neighborhood-level indicators linked with the highest adjusted elevations in risk were: Proportion of inhabitants aged 18–22 years who did not complete primary school before age 18 (adjusted IRR 1.23; 1.20–1.27); Proportion of inhabitants convicted for any violent crime (adjusted IRR 1.19; 1.16–1.23); and Proportion of inhabitants convicted for any crime resulting in a custodial sentence (adjusted IRR 1.15; 1.12–1.18).</div></div><div><h3>Conclusion</h3><div>This novel population-based multilevel analysis has evidenced the independent associations of neighborhood-level deprivation indicators on schizophrenia risk elevation. Replication is needed in other populations to inform the refinement of preventive strategies.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 52-59"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010749","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}
Min Xu , Dexiu Gao , Ailing Hu , Hua Qian , Yifeng Hao , Yajie Yan , Lina Gu , Chenxia Song , Ningning Zhu
{"title":"Social isolation and its influencing factors among family caregivers of individuals with schizophrenia: A social-ecological systems theory perspective","authors":"Min Xu , Dexiu Gao , Ailing Hu , Hua Qian , Yifeng Hao , Yajie Yan , Lina Gu , Chenxia Song , Ningning Zhu","doi":"10.1016/j.schres.2025.09.005","DOIUrl":"10.1016/j.schres.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Social isolation adversely affects both physical and mental health. However, limited research has examined this issue among family caregivers of individuals with schizophrenia, particularly within a structured theoretical framework.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the prevalence of social isolation and explore its associated multilevel factors among family caregivers of individuals with schizophrenia, guided by the Social-Ecological Systems Theory.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted following STROBE guidelines. A total of 267 schizophrenia patients and their primary family caregivers were recruited from a tertiary psychiatric hospital in China using consecutive sampling. Data were collected via self-reported questionnaires, including demographic and clinical information, the World Health Organization Quality of Life-BREF (WHOQOL-BREF), the Perceived Devaluation-Discrimination Scale (PDD), and the Lubben Social Network Scale-6 (LSNS-6). Descriptive statistics, Pearson correlation, univariate analysis, and multivariate linear regression were used to identify factors associated with social isolation.</div></div><div><h3>Results</h3><div>The mean LSNS-6 score was 12.56 (SD = 5.49), and 44.9 % of caregivers were classified as socially isolated. At the microsystem (individual) level, being employed (<em>β</em> = 0.181, <em>p</em> = 0.002) and having a better understanding of the disease (<em>β</em> = 0.107, <em>p</em> = 0.043) were significantly associated with lower levels of isolation. At the mesosystem (interpersonal) level, participation in social activities (<em>β</em> = 0.12, <em>p</em> = 0.046) and higher scores on the WHOQOL-BREF social relationships domain (<em>β</em> = 0.249, <em>p</em> = 0.004) were also associated with lower levels of isolation. At the macrosystem (policy and cultural) level, greater availability of residential mental health resources (<em>β</em> = 0.142, <em>p</em> = 0.018) and lower perceived stigma (PDD score, <em>β</em> = −0.124, <em>p</em> = 0.024) were associated with reduced isolation. These factors collectively accounted for 36 % of the variance in social isolation (adjusted <em>R</em><sup><em>2</em></sup> = 0.32).</div></div><div><h3>Conclusion</h3><div>Social isolation is prevalent among schizophrenia caregivers and is associated with multilevel factors. Interventions targeting caregiver psychoeducation and employment (microsystem), promoting social participation (mesosystem), and advancing anti-stigma efforts and residential mental health service accessibility (macrosystem) are critical to reducing isolation and improving caregiver well-being.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 30-38"},"PeriodicalIF":3.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004947","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}
Elena I. Ivleva , Jayme M. Palka , Anastasia M. Bobilev , Yan Fang , Carolyn Sacco , Alexa Ciarolla , Sina Aslan , Peiying Liu , Hanzhang Lu , Carol A. Tamminga
{"title":"Hippocampal subfield activity in schizophrenia: Effects of the disease course","authors":"Elena I. Ivleva , Jayme M. Palka , Anastasia M. Bobilev , Yan Fang , Carolyn Sacco , Alexa Ciarolla , Sina Aslan , Peiying Liu , Hanzhang Lu , Carol A. Tamminga","doi":"10.1016/j.schres.2025.09.004","DOIUrl":"10.1016/j.schres.2025.09.004","url":null,"abstract":"<div><div>Alterations in hippocampal structure and function are established in schizophrenia. However, the specific patterns of hippocampal activity along the schizophrenia course remain unknown. Eighty-five study participants [34 schizophrenia probands (SZ), 32 first-degree relatives (REL), 19 healthy controls (HC)] underwent 3Tesla ultra-high resolution brain MRI (Vascular Space Occupancy); relative cerebral blood volume (rCBV)—an index of regional activity—was estimated across hippocampal subfields: dentate gyrus (DG), CA3, CA1, and subiculum (SUB). To examine effects of the schizophrenia course, SZ were stratified into SZ-Early (≤7 yrs. from psychosis onset), SZ-Mid-Course (8-14 yrs) and SZ-Advanced (≥15 yrs). REL were grouped into those with (REL<img>P) and without (REL-NP) psychosis spectrum disorders. Medication effects were examined by contrasting SZ on- vs. off-antipsychotics. No hippocampal rCBV differences emerged in SZ vs. HC or in SZ-on vs. SZ-off antipsychotic medications. However, among the SZ course groups, SZ-Early showed elevated rCBV in CA3, CA1 and DG compared to SZ-Advanced and HC (<em>p</em> = .004–032). Illness duration-based cross-sectional “trajectories” demonstrated elevated hippocampal rCBV within the initial 7 yrs., followed by an intermediary plateau (8-20 yrs), and a subsequent decline in advanced (20+ yrs) SZ. Among biological relatives of SZ, REL-P vs. HC showed reduced rCBV in SUB, CA1 and DG (<em>p</em> = .021–0.046). Our findings demonstrate differential patterns of hippocampal rCBV along the schizophrenia course. Regional hippocampal activity may serve as a granular biomarker sensitive to the effects of the schizophrenia course and, via future work, inform SZ stage-specific interventions: e.g., reducing hippocampal hyperactivity in early-course SZ vs. enhancing this same circuit's function in advanced stages of SZ.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"285 ","pages":"Pages 39-51"},"PeriodicalIF":3.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004949","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}