The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation
Abstract 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 pat...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-025-00555-8 |
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| author | Zhenlei Peng Qiyu Jia Junxiong Mao Shijie Jiang Qi Ma Xiao Luo Zhiguo An Anqi Huang Chuang Ma Qizhong Yi |
| author_facet | Zhenlei Peng Qiyu Jia Junxiong Mao Shijie Jiang Qi Ma Xiao Luo Zhiguo An Anqi Huang Chuang Ma Qizhong Yi |
| author_sort | Zhenlei Peng |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-cfdaf7d3168444ab93cb400c5b17aed4 |
| institution | Kabale University |
| issn | 2754-6993 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Schizophrenia |
| spelling | doaj-art-cfdaf7d3168444ab93cb400c5b17aed42025-01-12T12:28:07ZengNature PortfolioSchizophrenia2754-69932025-01-0111111210.1038/s41537-025-00555-8The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigationZhenlei Peng0Qiyu Jia1Junxiong Mao2Shijie Jiang3Qi Ma4Xiao Luo5Zhiguo An6Anqi Huang7Chuang Ma8Qizhong Yi9Xinjiang Clinical Medical Research Center of Mental Health, The Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Trauma Orthopedics, The First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Psychiatry and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of MedicineXinjiang Clinical Medical Research Center of Mental Health, The Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical UniversityXinjiang Clinical Medical Research Center of Mental Health, State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityXinjiang Clinical Medical Research Center of Mental Health, The Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical UniversityXinjiang Clinical Medical Research Center of Mental Health, The Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical UniversityChild Mental Health Research Center, Nanjing Brain Hospital, Clinical Teaching Hospital of Medical School, Nanjing UniversityDepartment of Trauma Orthopedics, The First Affiliated Hospital of Xinjiang Medical UniversityXinjiang Clinical Medical Research Center of Mental Health, State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, The Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical UniversityAbstract 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.https://doi.org/10.1038/s41537-025-00555-8 |
| spellingShingle | Zhenlei Peng Qiyu Jia Junxiong Mao Shijie Jiang Qi Ma Xiao Luo Zhiguo An Anqi Huang Chuang Ma Qizhong Yi The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation Schizophrenia |
| title | The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation |
| title_full | The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation |
| title_fullStr | The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation |
| title_full_unstemmed | The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation |
| title_short | The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation |
| title_sort | role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients a multicenter investigation |
| url | https://doi.org/10.1038/s41537-025-00555-8 |
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