Pub Date : 2026-01-26DOI: 10.1016/j.schres.2026.01.014
Lais Fonseca , Lucas Toshio Ito , Carolina Ziebold , Luis A. Rohde , Eurípedes C. Miguel , Rodrigo A. Bressan , Pedro M. Pan , Sintia I. Belangero , Marcos L. Santoro , Felipe V. Gomes , Anthony A. Grace , Ary Gadelha
Background
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.
Study design
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.
Study results
PRS-SZ predicted lower EF scores (β = −0.091, t = −2.435, p = 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.
Conclusions
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.
{"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 , Lucas Toshio Ito , Carolina Ziebold , Luis A. Rohde , Eurípedes C. Miguel , Rodrigo A. Bressan , Pedro M. Pan , Sintia I. Belangero , Marcos L. Santoro , Felipe V. Gomes , Anthony A. Grace , 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":"2026-01-26","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}
Pub Date : 2026-01-26DOI: 10.1016/j.schres.2026.01.018
Vijay A. Mittal , Wing-Chung Chang , Elaine F. Walker
Negative symptoms are a core feature of schizophrenia and other psychoses that contribute substantially to functional disability but benefit little from standard treatment, thus representing an unmet therapeutic need. In fact, mechanisms underlying negative symptoms emerge in the early years of development and progress across various developmental stages of psychosis course. In premorbid period, subtle social withdrawal as well as deficits in emotion expression and social communication may represent early signals indicating vulnerability for a variety of disorders including schizophrenia. Attenuated negative symptoms, which manifest in the 5 consensus domains of anhedonia, avolition, asociality, alogia and blunted affect, are prevalent in prodromal period, predictive of conversion to full-blown psychosis, and associated with role and social dysfunction. Negative symptoms in both early psychosis and chronic schizophrenia are best conceptualized by the 5 consensus symptom domains. Greater severity of negative symptoms in first-episode psychosis is associated with more functional impairment, poorer premorbid adjustment and longer duration of untreated psychosis. There is progressive accrual of negative symptoms along the course of illness, in particular primary persistent negative symptoms which are more prevalent in the chronic illness stage, contributing to pronounced functional impairment and worse prognosis. In this article, we review the manifestations of negative symptoms in the context of developmental framework, highlighting the trajectory of negative symptoms across and the unique relevance for different stages of psychotic illness, as well as its relationships with functional disability, other illness-related factors, and treatment implications.
{"title":"Negative symptoms across developmental stages in psychosis spectrum","authors":"Vijay A. Mittal , Wing-Chung Chang , Elaine F. Walker","doi":"10.1016/j.schres.2026.01.018","DOIUrl":"10.1016/j.schres.2026.01.018","url":null,"abstract":"<div><div>Negative symptoms are a core feature of schizophrenia and other psychoses that contribute substantially to functional disability but benefit little from standard treatment, thus representing an unmet therapeutic need. In fact, mechanisms underlying negative symptoms emerge in the early years of development and progress across various developmental stages of psychosis course. In premorbid period, subtle social withdrawal as well as deficits in emotion expression and social communication may represent early signals indicating vulnerability for a variety of disorders including schizophrenia. Attenuated negative symptoms, which manifest in the 5 consensus domains of anhedonia, avolition, asociality, alogia and blunted affect, are prevalent in prodromal period, predictive of conversion to full-blown psychosis, and associated with role and social dysfunction. Negative symptoms in both early psychosis and chronic schizophrenia are best conceptualized by the 5 consensus symptom domains. Greater severity of negative symptoms in first-episode psychosis is associated with more functional impairment, poorer premorbid adjustment and longer duration of untreated psychosis. There is progressive accrual of negative symptoms along the course of illness, in particular primary persistent negative symptoms which are more prevalent in the chronic illness stage, contributing to pronounced functional impairment and worse prognosis. In this article, we review the manifestations of negative symptoms in the context of developmental framework, highlighting the trajectory of negative symptoms across and the unique relevance for different stages of psychotic illness, as well as its relationships with functional disability, other illness-related factors, and treatment implications.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 100-105"},"PeriodicalIF":3.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053788","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}
Pub Date : 2026-01-24DOI: 10.1016/j.schres.2026.01.012
L. Venet-Kelma , A. Abdel-Baki , A.-J. Romain
High-intensity interval training (HIIT) improves metabolic health, psychiatric symptoms, and functioning in individuals with psychotic disorders. However, research on the maintenance of HIIT benefits is limited. This study examines whether benefits were maintained six months post-supervised HIIT and identifies factors influencing their maintenance.
Sixty-six individuals (61% men; 30.73 ± 7.23 years old) with psychotic disorders participated in a 6-month supervised HIIT intervention (T1–T2), followed by a 6-month unsupervised period with free access to exercise facilities (T2–T3). Psychiatric symptoms and functioning were assessed at T1, T2, and T3. To examine the maintenance of supervised HIIT benefits, we used linear mixed model to compare scores between T1 and T3. To identify factors associated with maintenance of supervised HIIT benefits, participants were divided into two groups based on their attendance to T3 assessment. A one-way ANOVA compared these groups on psychiatric symptoms and functioning T2.
Benefits on negative (p = 0.01) and general (p = 0.03) symptoms observed at T2 were maintained at T3. Only younger age was significantly associated with HIIT benefit maintenance (p = 0.02).
Consistent with prior research, long-term benefits were observed only for negative and general symptoms. Neither functioning nor symptoms predicted maintenance of supervised HIIT benefits. Lack of improvement in functioning may relate to the absence of social components in the PA intervention. Also, missing data on physical activity during the follow-up period limits interpretation. Finally, future studies should assess the role of continued physical activity and social factors in sustaining benefits.
{"title":"What beneficial effects were maintained following a supervised high intensity interval training intervention among overweight individuals with psychotic disorders?","authors":"L. Venet-Kelma , A. Abdel-Baki , A.-J. Romain","doi":"10.1016/j.schres.2026.01.012","DOIUrl":"10.1016/j.schres.2026.01.012","url":null,"abstract":"<div><div>High-intensity interval training (HIIT) improves metabolic health, psychiatric symptoms, and functioning in individuals with psychotic disorders. However, research on the maintenance of HIIT benefits is limited. This study examines whether benefits were maintained six months post-supervised HIIT and identifies factors influencing their maintenance.</div><div>Sixty-six individuals (61% men; 30.73 ± 7.23 years old) with psychotic disorders participated in a 6-month supervised HIIT intervention (T1–T2), followed by a 6-month unsupervised period with free access to exercise facilities (T2–T3). Psychiatric symptoms and functioning were assessed at T1, T2, and T3. To examine the maintenance of supervised HIIT benefits, we used linear mixed model to compare scores between T1 and T3. To identify factors associated with maintenance of supervised HIIT benefits, participants were divided into two groups based on their attendance to T3 assessment. A one-way ANOVA compared these groups on psychiatric symptoms and functioning T2.</div><div>Benefits on negative (<em>p</em> = 0.01) and general (<em>p</em> = 0.03) symptoms observed at T2 were maintained at T3. Only younger age was significantly associated with HIIT benefit maintenance (<em>p</em> = 0.02).</div><div>Consistent with prior research, long-term benefits were observed only for negative and general symptoms. Neither functioning nor symptoms predicted maintenance of supervised HIIT benefits. Lack of improvement in functioning may relate to the absence of social components in the PA intervention. Also, missing data on physical activity during the follow-up period limits interpretation. Finally, future studies should assess the role of continued physical activity and social factors in sustaining benefits.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 1-8"},"PeriodicalIF":3.5,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039936","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}
Pub Date : 2026-01-22DOI: 10.1016/j.schres.2026.01.011
Ling Chan Wang , An Kun Lu , Zhen Hua Zhu , Wen Long Hou , Xuyuan Yin , Qing Yang , Li Juan Man , Jie Chen , Hong Liang Zhu , Xin Yu , Huiping Zhang , Li Hui
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, p = 0.003). Moreover, plasma Log10DBH levels showed a positive correlation with immediate memory score in patients (r = 0.27, p = 0.04). Linear regression further confirmed a significant association between Log10DBH levels and immediate memory score in patients (β = 50.18, t = 2.82, p = 0.008). Additionally, FDS patients scored significantly lower than HCs on the RBANS total score and all subdomains, except visuospatial/constructional score (all, p < 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.
多巴胺β-羟化酶（DBH）是一种催化多巴胺（DA）转化为去甲肾上腺素（NE）的酶。这些神经递质的失调与精神分裂症的病因和认知障碍有关。然而，DBH与精神分裂症的认知障碍之间的关系，独立于药物和慢性疾病的混杂作用，仍然不清楚。因此，本病例对照研究旨在探讨首发drug-naïve精神分裂症（FDS）患者血浆DBH水平、认知表现及其相关性。共入组56例FDS患者和56例年龄和性别匹配的健康对照（hc）。使用神经心理状态评估可重复电池（rban）评估认知功能，并通过夹心酶联免疫吸附试验（elisa）测量血浆DBH水平。校正协变量后，FDS患者血浆Log10DBH水平显著低于hcc患者（F = 9.17, p = 0.003）。血浆Log10DBH水平与患者即时记忆评分呈正相关（r = 0.27, p = 0.04）。线性回归进一步证实了Log10DBH水平与患者即时记忆评分之间的显著相关性（β = 50.18, t = 2.82, p = 0.008）。此外，FDS患者在rban总分和所有子域上的得分显著低于hc，除了视觉空间/结构得分（均，p < 0.001）。这些发现表明，血浆DBH水平降低可能与精神分裂症密切相关，并可能导致FDS患者的即时记忆障碍。
{"title":"Association between reduced plasma dopamine β-hydroxylase levels and immediate memory impairment in first-episode drug-naïve schizophrenia","authors":"Ling Chan Wang , An Kun Lu , Zhen Hua Zhu , Wen Long Hou , Xuyuan Yin , Qing Yang , Li Juan Man , Jie Chen , Hong Liang Zhu , Xin Yu , Huiping Zhang , 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 Log<sub>10</sub>DBH levels were significantly lower in FDS patients compared to HCs (F = 9.17, <em>p</em> = 0.003). Moreover, plasma Log<sub>10</sub>DBH 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 Log<sub>10</sub>DBH 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> < 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":"2026-01-22","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}
Pub Date : 2026-01-21DOI: 10.1016/j.schres.2026.01.013
Mohammed A. Mashal , Cathy S. Chen , Ian S. Ramsay , Sophia Vinogradov , Caroline Demro
{"title":"Letter to the editor: Enhancing cognitive control in schizophrenia with transcranial direct current stimulation and targeted cognitive training","authors":"Mohammed A. Mashal , Cathy S. Chen , Ian S. Ramsay , Sophia Vinogradov , Caroline Demro","doi":"10.1016/j.schres.2026.01.013","DOIUrl":"10.1016/j.schres.2026.01.013","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 89-93"},"PeriodicalIF":3.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030513","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}
Pub Date : 2026-01-20DOI: 10.1016/j.schres.2026.01.010
Haitao Chen , Hong Xiang , Meng Zhang , Yun Wen , Shiyou Tang , Shuping Tan , Jiahua Xu
Background
The glymphatic system's role in early schizophrenia remains unclear. This study investigated glymphatic function using the DTI-ALPS index in first-episode schizophrenia (FES), exploring its relationships with clinical features, antipsychotic treatment, and cognitive function.
Methods
The study included 37 first-episode drug-naïve (FESDN) patients, 22 first-episode treated (FEST) patients, and 42 demographically matched healthy controls (HCs). ALPS indices were calculated, and clinical assessments included cognitive function (RBANS), psychiatric symptoms (PANSS), and peripheral biomarkers.
Results
FES patients exhibited left-hemisphere predominant reductions in ALPS indices (p < 0.01). An interaction was observed between disease duration and treatment: the FEST group had lower DTI-ALPS than the FESDN group in patients with shorter illness durations, but this group difference diminished with longer disease duration (βinter = −0.8 × 10–2, p < 0.05). The ALPS-cognition association pattern differed between patients and HCs: left ALPS was positively correlated with RBANS in HCs (βHC > 0, p < 0.01) but negatively correlated in FES patients (βFESDN = −16.6, βFEST = −21.6, p < 0.1). Peripheral white blood cell count and total bilirubin were negatively associated with left ALPS in the FEST group (WBC: β = −0.63 × 10–2, p = 0.025; TBIL: β = −0.80 × 10–2, p = 0.039), with significant group interaction effects (p < 0.05).
Conclusion
FES patients demonstrate left-lateralized glymphatic dysfunction, the severity of which is dynamically modulated by treatment and disease duration. The observed negative ALPS‑cognition correlation raises the possibility of a compensatory mechanism in early schizophrenia. Associations noted between peripheral inflammatory/metabolic markers and ALPS offer tentative support for an interactive “periphery–brain” clearance system. DTI-ALPS may serve as a dynamic biomarker reflecting neuropathological mechanisms in early schizophrenia.
背景：淋巴系统在早期精神分裂症中的作用尚不清楚。本研究采用DTI-ALPS指数对首发精神分裂症（FES）患者的淋巴功能进行了研究，探讨其与临床特征、抗精神病药物治疗和认知功能的关系。方法：该研究包括37例首发drug-naïve （FESDN）患者，22例首发治疗（FEST）患者和42例人口统计学匹配的健康对照（hc）。计算ALPS指数，临床评估包括认知功能（rban）、精神症状（PANSS）和外周生物标志物。结果：FES患者表现为左半球主要的ALPS指数下降（p -2, p -0, p -2, p = 0.025; TBIL: β = -0.80 × 10-2, p = 0.039），组间相互作用显著(p)。结论：FES患者表现为左偏侧淋巴功能障碍，其严重程度随治疗和病程动态调节。观察到的负的ALPS -认知相关性提出了早期精神分裂症代偿机制的可能性。外周炎症/代谢标志物与ALPS之间的关联为“外周-脑”互动清除系统提供了初步支持。DTI-ALPS可能是反映早期精神分裂症神经病理机制的动态生物标志物。
{"title":"Antipsychotic-disease duration interaction on glymphatic function in first-episode schizophrenia: Evidence from DTI-ALPS","authors":"Haitao Chen , Hong Xiang , Meng Zhang , Yun Wen , Shiyou Tang , Shuping Tan , Jiahua Xu","doi":"10.1016/j.schres.2026.01.010","DOIUrl":"10.1016/j.schres.2026.01.010","url":null,"abstract":"<div><h3>Background</h3><div>The glymphatic system's role in early schizophrenia remains unclear. This study investigated glymphatic function using the DTI-ALPS index in first-episode schizophrenia (FES), exploring its relationships with clinical features, antipsychotic treatment, and cognitive function.</div></div><div><h3>Methods</h3><div>The study included 37 first-episode drug-naïve (FESDN) patients, 22 first-episode treated (FEST) patients, and 42 demographically matched healthy controls (HCs). ALPS indices were calculated, and clinical assessments included cognitive function (RBANS), psychiatric symptoms (PANSS), and peripheral biomarkers.</div></div><div><h3>Results</h3><div>FES patients exhibited left-hemisphere predominant reductions in ALPS indices (<em>p</em> < 0.01). An interaction was observed between disease duration and treatment: the FEST group had lower DTI-ALPS than the FESDN group in patients with shorter illness durations, but this group difference diminished with longer disease duration (βinter = −0.8 × 10<sup>–2</sup>, <em>p</em> < 0.05). The ALPS-cognition association pattern differed between patients and HCs: left ALPS was positively correlated with RBANS in HCs (βHC > 0, <em>p</em> < 0.01) but negatively correlated in FES patients (βFESDN = −16.6, βFEST = −21.6, <em>p</em> < 0.1). Peripheral white blood cell count and total bilirubin were negatively associated with left ALPS in the FEST group (WBC: β = −0.63 × 10<sup>–2</sup>, <em>p</em> = 0.025; TBIL: β = −0.80 × 10<sup>–2</sup>, <em>p</em> = 0.039), with significant group interaction effects (<em>p</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>FES patients demonstrate left-lateralized glymphatic dysfunction, the severity of which is dynamically modulated by treatment and disease duration. The observed negative ALPS‑cognition correlation raises the possibility of a compensatory mechanism in early schizophrenia. Associations noted between peripheral inflammatory/metabolic markers and ALPS offer tentative support for an interactive “periphery–brain” clearance system. DTI-ALPS may serve as a dynamic biomarker reflecting neuropathological mechanisms in early schizophrenia.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 79-88"},"PeriodicalIF":3.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019515","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}
Pub Date : 2026-01-19DOI: 10.1016/j.schres.2026.01.009
Mikaela Bere , Susan L. Rossell , Denny Meyer , Julia D. Nicholls , Stephen Halperin , Wei Lin Toh
It is widely acknowledged that trauma is related to auditory hallucinations in psychotic disorders. Yet, this relationship has not been well explored in hallucinations across other sensory modalities. The current study investigated whether hallucination modality groups (auditory, visual, olfactory, tactile, multisensory) were significantly related to physical, sexual, or emotional trauma. The age at which the trauma was experienced (16 or below, 17 and above) was also considered. Multivariate linear models, analysis of variance, and regression analyses for sixty-six participants with a psychotic disorder sought to determine whether trauma was related to hallucinations. Specifically, we used a modified version of the Life-Stressor Checklist Revised and the Multimodal Hallucinations Schedule (MHS) to identify whether the number of trauma items endorsed, or severity of trauma, at different developmental stages were significantly associated with the severity of lifetime hallucinations across different modalities, and the number of hallucination modalities experienced. We found that the severity of visual hallucinations was significantly associated with a history of sexual trauma. Notably, we revealed that experiencing sexual trauma in both childhood and adulthood was related to an increased self-reported severity of the trauma, and possibly the severity of visual hallucinations. These preliminary findings suggest that type of trauma may be uniquely related to specific hallucination modality and severity. Further, it is important to consider adulthood traumas as well as those occurring in childhood. These results have implications for clinical assessment and intervention.
{"title":"Trauma and hallucinations across the sensory modalities: the importance of considering experiences in childhood and adulthood","authors":"Mikaela Bere , Susan L. Rossell , Denny Meyer , Julia D. Nicholls , Stephen Halperin , Wei Lin Toh","doi":"10.1016/j.schres.2026.01.009","DOIUrl":"10.1016/j.schres.2026.01.009","url":null,"abstract":"<div><div>It is widely acknowledged that trauma is related to auditory hallucinations in psychotic disorders. Yet, this relationship has not been well explored in hallucinations across other sensory modalities. The current study investigated whether hallucination modality groups (auditory, visual, olfactory, tactile, multisensory) were significantly related to physical, sexual, or emotional trauma. The age at which the trauma was experienced (16 or below, 17 and above) was also considered. Multivariate linear models, analysis of variance, and regression analyses for sixty-six participants with a psychotic disorder sought to determine whether trauma was related to hallucinations. Specifically, we used a modified version of the Life-Stressor Checklist Revised and the Multimodal Hallucinations Schedule (MHS) to identify whether the number of trauma items endorsed, or severity of trauma, at different developmental stages were significantly associated with the severity of lifetime hallucinations across different modalities, and the number of hallucination modalities experienced. We found that the severity of visual hallucinations was significantly associated with a history of sexual trauma. Notably, we revealed that experiencing sexual trauma in both childhood and adulthood was related to an increased self-reported severity of the trauma, and possibly the severity of visual hallucinations. These preliminary findings suggest that type of trauma may be uniquely related to specific hallucination modality and severity. Further, it is important to consider adulthood traumas as well as those occurring in childhood. These results have implications for clinical assessment and intervention.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 71-78"},"PeriodicalIF":3.5,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012161","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}
Pub Date : 2026-01-17DOI: 10.1016/j.schres.2026.01.002
Özgü Şişman , Sinay Önen
Objective
This study aimed to investigate the prevalence of sarcopenia in individuals with schizophrenia and examine its associations with oxidative stress, symptom severity, functioning, and quality of life.
Methods
A total of 198 schizophrenia patients aged 18–65 were assessed using the EWGSOP2 criteria for sarcopenia. Participants were classified as sarcopenic if they met criteria for probable, confirmed, or severe sarcopenia. Oxidative stress was evaluated using total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI). Clinical functioning, psychiatric symptoms, and quality of life were assessed using standardized psychometric tools. Multiple linear regression was conducted to identify predictors of oxidative stress parameters.
Results
Sarcopenia was identified in 66.6% of participants, with most meeting criteria for probable sarcopenia. Sarcopenic patients had significantly lower muscle mass, bone mass, basal metabolic rate, handgrip strength, and walking speed, along with poorer quality of life and functional scores. TAC positively correlated with muscle-related parameters and inversely with sarcopenia severity, while OSI showed negative correlations with physical health indicators. Sarcopenic patients also had more severe psychiatric symptoms. Regression analysis revealed that TAC was significantly predicted by BMI, the number of sarcopenia criteria met, PANSS-Total, and WHOQOL-BREF scores (R2 = 0.10, p = .011). No significant differences were found in mean TAC, TOS, and OSI between sarcopenic and non-sarcopenic groups.
Conclusion
Sarcopenia is highly prevalent and clinically relevant in individuals with schizophrenia, even at midlife. Routine screening and early interventions targeting physical health and oxidative stress may improve outcomes.
目的本研究旨在调查精神分裂症患者肌肉减少症的患病率，并研究其与氧化应激、症状严重程度、功能和生活质量的关系。方法采用EWGSOP2肌少症诊断标准对198例18 ~ 65岁精神分裂症患者进行评估。如果参与者符合可能的、确诊的或严重的肌肉减少症标准，则将其分类为肌肉减少症。采用总抗氧化能力（TAC）、总氧化状态（TOS）和氧化应激指数（OSI）评价氧化应激。使用标准化的心理测量工具评估临床功能、精神症状和生活质量。采用多元线性回归确定氧化应激参数的预测因子。结果66.6%的参与者出现肌肉减少症，大多数符合可能的肌肉减少症标准。肌肉减少症患者的肌肉量、骨量、基础代谢率、握力和步行速度明显降低，生活质量和功能评分也较差。TAC与肌肉相关参数正相关，与肌少症严重程度负相关，而OSI与身体健康指标负相关。肌肉减少症患者也有更严重的精神症状。回归分析显示，BMI、满足肌少症标准数、PANSS-Total和WHOQOL-BREF评分对TAC有显著预测作用（R2 = 0.10, p = 0.011）。在肌肉减少组和非肌肉减少组之间，平均TAC、TOS和OSI没有显著差异。结论骨骼肌减少症在精神分裂症患者中非常普遍且具有临床相关性，甚至在中年患者中也是如此。针对身体健康和氧化应激的常规筛查和早期干预可能改善结果。
{"title":"Prevalence and multidimensional impact of sarcopenia in schizophrenia: Associations with oxidative stress, functioning, and symptom severity","authors":"Özgü Şişman , 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 (R<sup>2</sup> = 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":"2026-01-17","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}
Pub Date : 2026-01-16DOI: 10.1016/j.schres.2026.01.004
Roberta Cessa , Andrea Ghiani , Ezgi Cenk , Marco Bertamini
Perceptual organization (PO) deficits have long been considered a hallmark of schizophrenia (SZ), reflecting disruptions in the integration of visual information. This systematic review critically evaluates the behavioral evidence for PO impairments in SZ and individuals with high schizotypal traits, focusing on three key mid-level processes: contour integration, perceptual grouping, and figure-ground segmentation. Forty-four studies were included, identified through a systematic search and evaluated for bias using the QUADAS-2 tool.
Findings reveal robust and replicable deficits in contour integration among individuals with SZ, especially in those with disorganization symptoms, suggesting impaired lateral interactions in early visual areas. Perceptual grouping deficits were also prominent but appeared more sensitive to cognitive load and stimulus complexity, consistent with top-down integration failures. Figure-ground segmentation impairments were less consistently reported and often dependent on task demands, emerging more clearly under challenging conditions.
In schizotypy, evidence of PO deficits was more variable. Some studies identified subtle impairments in contour integration and grouping, particularly under high attentional load or in individuals with disorganized traits, while others reported intact performance. The heterogeneity of methods across studies, particularly differences in stimulus type, complexity, and grouping cues, was a major limiting factor for cross-study comparisons.
Findings from this review support a dimensional view of PO deficits, where specific symptom clusters, rather than diagnosis alone, predict perceptual dysfunction. PO impairments, particularly in contour integration, may serve as sensitive cognitive markers for early detection and targeted intervention in SZ-spectrum disorders.
{"title":"Perceptual organization and its visual subcomponents in schizophrenia and schizotypy: A systematic review","authors":"Roberta Cessa , Andrea Ghiani , Ezgi Cenk , Marco Bertamini","doi":"10.1016/j.schres.2026.01.004","DOIUrl":"10.1016/j.schres.2026.01.004","url":null,"abstract":"<div><div>Perceptual organization (PO) deficits have long been considered a hallmark of schizophrenia (SZ), reflecting disruptions in the integration of visual information. This systematic review critically evaluates the behavioral evidence for PO impairments in SZ and individuals with high schizotypal traits, focusing on three key mid-level processes: contour integration, perceptual grouping, and figure-ground segmentation. Forty-four studies were included, identified through a systematic search and evaluated for bias using the QUADAS-2 tool.</div><div>Findings reveal robust and replicable deficits in contour integration among individuals with SZ, especially in those with disorganization symptoms, suggesting impaired lateral interactions in early visual areas. Perceptual grouping deficits were also prominent but appeared more sensitive to cognitive load and stimulus complexity, consistent with top-down integration failures. Figure-ground segmentation impairments were less consistently reported and often dependent on task demands, emerging more clearly under challenging conditions.</div><div>In schizotypy, evidence of PO deficits was more variable. Some studies identified subtle impairments in contour integration and grouping, particularly under high attentional load or in individuals with disorganized traits, while others reported intact performance. The heterogeneity of methods across studies, particularly differences in stimulus type, complexity, and grouping cues, was a major limiting factor for cross-study comparisons.</div><div>Findings from this review support a dimensional view of PO deficits, where specific symptom clusters, rather than diagnosis alone, predict perceptual dysfunction. PO impairments, particularly in contour integration, may serve as sensitive cognitive markers for early detection and targeted intervention in SZ-spectrum disorders.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 46-60"},"PeriodicalIF":3.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981464","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}
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