Schizophrenia (Heidelberg, Germany)最新文献

{"title":"Identifying neurobiological heterogeneity in clinical high-risk psychosis: a data-driven biotyping approach using resting-state functional connectivity.","authors":"Xiaochen Tang, Yanyan Wei, Jiaoyan Pang, Lihua Xu, Huiru Cui, Xu Liu, Yegang Hu, Mingliang Ju, Yingying Tang, Bin Long, Wei Liu, Min Su, Tianhong Zhang, Jijun Wang","doi":"10.1038/s41537-025-00565-6","DOIUrl":"10.1038/s41537-025-00565-6","url":null,"abstract":"<p><p>To explore the neurobiological heterogeneity within the Clinical High-Risk (CHR) for psychosis population, this study aimed to identify and characterize distinct neurobiological biotypes within CHR using features from resting-state functional networks. A total of 239 participants from the Shanghai At Risk for Psychosis (SHARP) program were enrolled, consisting of 151 CHR individuals and 88 matched healthy controls (HCs). Functional connectivity (FC) features that were correlated with symptom severity were subjected to the single-cell interpretation through multikernel learning (SIMLR) algorithm in order to identify latent homogeneous subgroups. The cognitive function, clinical symptoms, FC patterns, and correlation with neurotransmitter systems of biotype profiles were compared. Three distinct CHR biotypes were identified based on 646 significant ROI-ROI connectivity features, comprising 29.8%, 19.2%, and 51.0% of the CHR sample, respectively. Despite the absence of overall FC differences between CHR and HC groups, each CHR biotype demonstrated unique FC abnormalities. Biotype 1 displayed augmented somatomotor connection, Biotype 2 shown compromised working memory with heightened subcortical and network-specific connectivity, and Biotype 3, characterized by significant negative symptoms, revealed extensive connectivity reductions along with increased limbic-subcortical connectivity. The neurotransmitter correlates differed across biotypes. Biotype 2 revealed an inverse trend to Biotype 3, as increased neurotransmitter concentrations improved functional connectivity in Biotype 2 but reduced it in Biotype 3. The identification of CHR biotypes provides compelling evidence for the early manifestation of heterogeneity within the psychosis spectrum, suggesting that distinct pathophysiological mechanisms may underlie these subgroups.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"13"},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based prediction of antipsychotic efficacy from brain gray matter structure in drug-naive first-episode schizophrenia.","authors":"Xiaodong Guo, Enpeng Zhou, Xianghe Wang, Bingjie Huang, Tianqi Gao, Chengcheng Pu, Xin Yu","doi":"10.1038/s41537-025-00557-6","DOIUrl":"10.1038/s41537-025-00557-6","url":null,"abstract":"<p><p>Predicting patient response to antipsychotic medication is a major challenge in schizophrenia treatment. This study investigates the predictive role of gray matter (GM) in short- and long-term treatment outcomes in drug-naive patients with first-episode schizophrenia (FES). A cohort of 104 drug-naive FES was recruited. Before initiating treatment, T1-weighted anatomical images were captured. The Positive and Negative Syndrome Scale and the Personal and Social Performance Scale were adopted to assess clinical symptoms and social function. At the 3-month follow-up, patients were categorized into remission and non-remission groups. At 1-year follow-up, patients were categorized into the rehabilitation and non-rehabilitation groups. Machine learning algorithms were applied to predict treatment outcomes based on GM volume, cortical thickness, and gyrification index, and the model performance was evaluated. Widespread regions, such as the superior temporal gyrus, middle frontal gyrus, supramarginal gyrus, the posterior central gyrus, anterior cingulate gyrus, and parahippocampal gyrus showed substantial predictive value for 3-month treatment efficacy (74.32% accuracy). The inferior frontal gyrus, anterior cingulate gyrus, and inferior occipital gyrus demonstrated significant predictive power for treatment outcome at 1-year follow-up (70.31% accuracy). We developed a machine learning model to predict individual responses to antipsychotic treatments, which could positively impact clinical treatment protocols for schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"11"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of avatar identity on spontaneous perspective-taking in patients with schizophrenia.","authors":"Pei Xie, ChaoZheng Huang, XiaoQuan Wang, HanBin Sang, AiBao Zhou","doi":"10.1038/s41537-024-00551-4","DOIUrl":"10.1038/s41537-024-00551-4","url":null,"abstract":"<p><p>Controversy exists regarding whether the spontaneity of altercentric intrusion is impaired in patients with schizophrenia during implicit visual perspective-taking tasks. This study explored the characteristics of spontaneous visual perspective-taking in patients with schizophrenia and the effect of an avatar identity on their perspective-taking. We recruited 65 patients with schizophrenia and 65 healthy participants to complete 4 visual perspective-taking experiments for uncued other-avatar and self-avatar tasks and cued other-avatar and self-avatar tasks. In uncued other-avatar experiments, healthy controls showed a significant reduction in accuracy and an increase in response latency when the number of visible discs differed from that seen by the other-avatar (inconsistent condition), indicating altercentric intrusion. However, patients with schizophrenia did not exhibit this effect. In uncued self-avatar experiments, when the avatar was defined as the participant themselves, patients with schizophrenia did not show spontaneous perspective-taking. However, in cued other-avatar experiments, they showed altercentric intrusion in response latency, and in cued self-avatar experiments, they showed altercentric intrusion in accuracy and response latency. These results suggest that patients with schizophrenia have the tendency to spontaneously adopt the perspective of others, which is predicated on their awareness of the existence of perspectives. In addition, the avatar's identity as a stranger hinders the spontaneous perspective-taking processes in patients with schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"9"},"PeriodicalIF":3.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring genetic associations and drug targets for mitochondrial proteins and schizophrenia risk.","authors":"Wenxi Sun, Ping Sun, Jin Li, Qun Yang, Qing Tian, Shiting Yuan, Xueying Zhang, Peng Chen, Chuanwei Li, Xiaobin Zhang","doi":"10.1038/s41537-025-00559-4","DOIUrl":"10.1038/s41537-025-00559-4","url":null,"abstract":"<p><p>Numerous observational studies have highlighted associations between mitochondrial dysfunction and schizophrenia (SCZ), yet the causal relationship remains elusive. This study aims to elucidate the causal link between mitochondria-associated proteins and SCZ. We used summary data from a genome-wide association study (GWAS) of 66 mitochondria-associated proteins in 3,301 individuals from Europe, as well as a GWAS on the large, multi-ethnic ancestry of SCZ, involving 76,755 cases and 243,649 controls. We conducted bidirectional two-sample Mendelian randomization (MR) analyses, with inverse variance weighting (IVW) as the primary method. To account for multi-directionality and ensure robustness, we included MR-Egger, weighted median (WM), weighted mode, and simple mode methods as supplementary sensitivity analyses. Moreover, we explored the GWAS catalog and the Drug-Gene Interaction Database (DGIdb) to identify and evaluate potential therapeutic targets. MR analysis revealed significant genetically determined causal associations between ETHE1 (OR: 1.06), SOD (OR: 0.97), CALU3 (OR: 1.03), and C1QBP (OR: 1.05) and SCZ. According to the reverse MR analysis, a causal relationship was shown between SCZ and CA5A (OR: 1.09), DLD (OR: 1. 08), AIF1 (OR: 0.93), SerRS (OR: 0.93) and MULA of NFKB1 (OR: 0.77). After conducting the gene-drug analysis, HRG, F12, GPLD1, C1R, BCHE, CFH, PON1, and CA5A were identified as promising therapeutic targets. This present study reveals a significant causal relationship between mitochondria-associated proteins and SCZ, offering valuable insights into the disease's pathogenicity and identifying potential therapeutic targets for drug development.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"10"},"PeriodicalIF":3.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key regions aberrantly connected within cerebello-thalamo-cortical circuit and their genetic mechanism in schizophrenia: an fMRI meta-analysis and transcriptome study.","authors":"Yarui Wei, Ziyu Wang, Kangkang Xue, Xiaoyu Niu, Longyao Ma, Shaoqiang Han, Baohong Wen, Yong Zhang, Huafu Chen, Jingliang Cheng","doi":"10.1038/s41537-025-00558-5","DOIUrl":"10.1038/s41537-025-00558-5","url":null,"abstract":"<p><p>Recent studies have showed aberrant connectivity of cerebello-thalamo-cortical circuit (CTCC) in schizophrenia (SCZ), which might be a heritable trait. However, these individual studies vary greatly in their methods and findings, and important areas within CTCC and related genetic mechanism are unclear. We searched for consistent regions of circuit dysfunction using a functional magnetic resonance imaging (fMRI) meta-analysis, followed by meta-regression and functional annotation analysis. Gene annotation analysis was performed to identify genes over-expressed in these regions by using the Allen Human Brain Atlas, followed by a set of gene functional feature analyses. 19 studies (1333 patients and 1174 healthy controls) were included in this meta-analysis. SCZ was characterized by hyperconnectivity of the auditory network, visual system, and sensorimotor areas, and hypoconnectivity of the frontal gyrus, cerebellum, thalamus, and caudate nucleus, which were significantly linked to age, sex, duration of illness, and the severity of symptoms and functionally enriched in domains involving self, sensory, action, and social. 2922 genes were significantly over-expressed in these regions, which were enriched for important molecular functions, biological processes, and cellular components of the neurons/cells in the brain as well as SCZ and other mental diseases. These genes were specially expressed in the brain tissue, in the neurons of the cerebellum, subcortex and cortex and during nearly all developmental stages, and constructed a protein-protein interaction network supported by 85 hub genes with functional significance. These findings suggest key regions aberrantly connected within CTCC in SCZ, which may indicate the neural substrate of \"cognitive dysmetria\" and be a consequence of complex interactions from a wide range of genes with diverse functional features.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"8"},"PeriodicalIF":3.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered brain dynamics of facial emotion processing in schizophrenia: a combined EEG/fMRI study.","authors":"Philippa Hüpen, Barbara Schulte Holthausen, Christina Regenbogen, Thilo Kellermann, Han-Gue Jo, Ute Habel","doi":"10.1038/s41537-025-00553-w","DOIUrl":"10.1038/s41537-025-00553-w","url":null,"abstract":"<p><p>Facial stimuli are relevant social cues for humans and essential signals for adequate social interaction. Impairments in face processing are well-documented in schizophrenia and linked to symptomatology, yet the underlying neural dynamics remain unclear. Here, we investigated the processing and underlying neural temporal dynamics of task-irrelevant emotional face stimuli using combined EEG/fMRI in 14 individuals with schizophrenia and 14 matched healthy controls. Specifically, fMRI-informed region-of-interests were subjected to EEG-Dynamic Causal Modeling (DCM) analyses. Among six fMRI-informed EEG-DCM models, alterations in effective connectivity emerged between the primary visual cortex (V1) and the left occipital fusiform gyrus (lOFG). Specifically, individuals with schizophrenia showed enhanced backward connectivity from the lOFG to V1 for stimuli preceded by fearful (but not happy or neutral) faces. Connectivity strength was strongly correlated with self-reported difficulties in comprehending, processing, or articulating emotions (as assessed by the Toronto Alexithymia Scale-20) in individuals with schizophrenia but not in healthy controls. Enhanced backward connectivity from the lOFG to V1 potentially indicates heightened attention towards fearful surroundings and a propensity to assign salience to these stimuli in individuals with schizophrenia. The link to TAS-20 scores indicates that this neural deficit has real-world implications for how individuals with schizophrenia perceive and relate to their emotions and the external world, potentially contributing to the social and cognitive difficulties observed in the disorder.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"6"},"PeriodicalIF":3.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased mortality risk in people with schizophrenia in Lithuania 2001-2020.","authors":"Mingaile Drevinskaite, Auguste Kaceniene, Arunas Germanavicius, Giedre Smailyte","doi":"10.1038/s41537-024-00549-y","DOIUrl":"10.1038/s41537-024-00549-y","url":null,"abstract":"<p><p>The aim of this study was to assess mortality risk in people with schizophrenia in Lithuania from 2001 and 2020. Cause-specific and all-cause mortality risk among patients with schizophrenia was assessed using a retrospective cohort study design. The cohort identified all patients with schizophrenia diagnosis (ICD-10 code F20) who were admitted to the Vilnius Republican Psychiatric Hospital from 1 January, 2001 to December 31, 2020. Dates of death and emigration were obtained from the Central Population Register. The standardized mortality ratios (SMRs) were calculated by dividing the observed number of deaths among patients with schizophrenia by the expected number of deaths, calculated using the national rates. The final cohort included 7883 patients, with 2458 observed deaths. An increased all-cause mortality risk was found for both sexes (SMR = 1.96; 95% CI 1.88-2.04) compared to the general population. The most common cause-specific mortality risk was found for diseases of the circulatory system (SMR = 2.17; 95% CI 2.05-2.30). Other significant increases in cause-specific mortality risk were observed for infectious diseases, mental and behavioural disorders, diseases of the nervous system and respiratory system, diseases of the genitourinary system, as well as external causes. Patients with schizophrenia do not benefit from the health strategies that have led to reduced mortality in the general population. To close the mortality gap, smoking and alcohol cessation interventions, cardiovascular and cancer screening and monitoring, early diagnosis, and interventions for identified physical diseases should be regarded as imperative.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"7"},"PeriodicalIF":3.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital health for early psychosis in Ghana: patient and caregiver needs and preferences.","authors":"Anna Larsen, Joel Agorinya, Alexa Beaulieu, Emmanuel Quame Sottie, Benjamin Buck, Kwadwo Obeng, Bill Kyeremeh, Fredrick Kwame Dogbe, Muhammed Izudeen Iddrisu, Phil Emil Okwei Dowuona, Olivia Oteba Abbey Tetteh, Omari Boakye Emmanuel, Angela Ofori-Atta, Dror Ben-Zeev","doi":"10.1038/s41537-025-00554-9","DOIUrl":"10.1038/s41537-025-00554-9","url":null,"abstract":"<p><p>In West Africa, the long-term consequences of poor early psychosis recovery include poverty, neglect, and community ostracization. To understand the potential for digital health approaches to support early psychosis care in Ghana, we conducted a survey study among early psychosis patients and their caregivers about mental health needs, technology use and access, and interest in digital mental health. Hospital staff at Accra Psychiatric Hospital reviewed hospital medical records from January 2023 - December 2023 identifying young adults (≥18 years old) who had experienced psychosis symptoms for the first time within the prior five years. Trained data assessors contacted these individuals via telephone and invited them and their caregivers to participate; those providing informed consent were interviewed via phone in Twi or English. Overall, 256 individuals participated in the survey, including 121 young adults experiencing early psychosis and 135 caregivers of early psychosis patients. The majority (80%) of early psychosis patients and their caregivers expressed interest in digital mental health for early psychosis and had access to a mobile phone (91%) and necessary mobile infrastructure. Early psychosis patients were most interested in information about managing stress and improving mood via a digital resource (72%). Caregivers desired a digital tool to provide information about psychosis symptoms (86%). Our study among those experiencing early psychosis and their caregivers in Ghana suggests readiness and acceptability of digital mental health for early psychosis care.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"5"},"PeriodicalIF":3.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life stress and functional connectivity in antipsychotic-naïve first episode psychosis patients.","authors":"Hillary N Patton, Jose O Maximo, James E Bryant, Adrienne C Lahti","doi":"10.1038/s41537-024-00552-3","DOIUrl":"10.1038/s41537-024-00552-3","url":null,"abstract":"<p><p>The neural mechanisms underlying the association between childhood trauma (CT) and psychosis spectrum disorders remains unclear. The objective of this study is to examine the relationship between childhood trauma and functional connectivity of fronto-limbic regions in a large sample of antipsychotic-naïve patients with first episode psychosis (FEP). Resting state fMRI data from 105 FEP patients and 123 healthy controls (HC) were used. Our regions of interest included bilateral hippocampus/amygdala and ventromedial prefrontal cortex (vmPFC). Childhood Trauma Questionnaire (CTQ) total and subscale scores were correlated with the resting state functional connectivity (rsFC) data. Partial correlation analyses indicated that higher CTQ sexual abuse subscale scores in FEP patients were associated with increased left amygdala-vmPFC rsFC (r(59) = 0.27, p < 0.05) and higher CTQ emotional neglect subscale scores in FEP patients were associated with increased left hippocampus-vmPFC rsFC (r(59) = 0.26, p < 0.05). Follow-up analysis showed a significant interaction effect of group (FEP and HC) and CTQ score (sexual abuse subscale) on left amygdala-vmPFC rsFC (β = 0.014, p < 0.05). Higher CTQ sexual abuse subscale scores were associated with increased rsFC in FEP patients (β = 0.56, p < 0.001). but reduced rsFC in healthy controls (β = -0.56, p < 0.001). The results also provide support for the long-term differential impact of trauma subtypes on the human brain. Overall, the results contribute to the understanding of the neural mechanisms underlying the association between childhood trauma and psychosis spectrum disorders.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"3"},"PeriodicalIF":3.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation.","authors":"Zhenlei Peng, Qiyu Jia, Junxiong Mao, Shijie Jiang, Qi Ma, Xiao Luo, Zhiguo An, Anqi Huang, Chuang Ma, Qizhong Yi","doi":"10.1038/s41537-025-00555-8","DOIUrl":"10.1038/s41537-025-00555-8","url":null,"abstract":"<p><p>Oxidative stress (OS) is crucial in schizophrenia (SCZ) pathology. Ferroptosis, a recently discovered cell death pathway linked to OS, might contribute to the development of SCZ. This study investigated the association between ferroptosis markers and cognitive impairments in chronic SCZ patients. A retrospective analysis was conducted on 204 chronic SCZ patients with cognitive deficits and 216 healthy controls (HC) matched for relevant characteristics. Plasma levels of ferroptosis and OS markers, including iron, ferritin (FE), transferrin (TF), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), glutathione (GSH), sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured. Standardized assessments like the positive and negative syndrome scale (PANSS), and Montreal Cognitive Assessment (MoCA) were used to evaluate psychiatric symptoms, and cognitive function. SCZ patients showed significant differences in markers compared to the HC group (P < 0.01). Multiple linear regression analysis revealed that decreased GSH and iron levels, along with elevated SOD levels, were significantly associated with the overall severity of psychiatric symptoms. Additionally, reduced GPX4 levels and increased ACSL4 and FE levels were significantly linked to negative symptoms and cognitive impairments. Notably, GPX4 emerged as a key predictor for cognitive function in abstraction and language domains. Our study revealed alterations in the altered plasma levels of GPX4, GSH, iron, ACSL4, FE, and SOD in chronic SCZ patients, which might indicate a close association between biomarkers of ferroptosis and OS and the psychiatric symptoms and cognitive deficits observed in these individuals.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"4"},"PeriodicalIF":3.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}