White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study
Abstract Background Studies have reported that white matter hyperintensities (WMHs) are associated with disturbances in immune function, and the relationship between WMHs and cognitive impairments have been documented in various clinical populations. The present study was to examine the relationship...
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BMC
2025-05-01
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| Series: | BMC Psychiatry |
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| Online Access: | https://doi.org/10.1186/s12888-025-06905-1 |
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| author | Yan Zhang Xiuxia Yuan Yu Zhang Yishao Chen Keju Su Kangkang Xue Suying Ding Jingfeng Chen Xiaoduo Fan Xueqin Song |
| author_facet | Yan Zhang Xiuxia Yuan Yu Zhang Yishao Chen Keju Su Kangkang Xue Suying Ding Jingfeng Chen Xiaoduo Fan Xueqin Song |
| author_sort | Yan Zhang |
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| description | Abstract Background Studies have reported that white matter hyperintensities (WMHs) are associated with disturbances in immune function, and the relationship between WMHs and cognitive impairments have been documented in various clinical populations. The present study was to examine the relationship between WMHs, immune function, and cognitive impairments in patients with schizophrenia (SCH) remains unknown. Methods A sample of 127 drug-naïve first episode SCH and 72 healthy controls (HCs) were included in this study. Serum levels of cytokines and oxidative stress indices were measured using enzyme-linked immunosorbent assay and microtiter plate method. WMHs were assessed using T2-weighted magnetic resonance imaging scanning, and cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery. Results We found patients with SCH are more likely to present with WMHs compared with HCs (OR = 2.076, 95%CI 1.007–4.277, p = 0.048). SCH with WMHs displayed more pronounced cognitive deficits in domains including speed of processing, working memory, verbal learning, visual learning, reasoning, and problem-solving compared with patients without WMHs (p < 0.05). Correlation analysis showed that the volume of WMHs was negative correlated with the problem-solving score (r=-0.331, p = 0.042) in patients with SCH. Within the SCH group, patients with WMHs exhibited elevated levels of interleukin-2 (IL-2), reactive oxygen species (ROS), and superoxide dismutase (SOD), along with lower levels of serum interleukin-4 (IL-4) and interferon-γ (IFN-γ) compared with those without WMHs (p < 0.05). The mediation analyses demonstrated that serum levels of IFN-γ in SCH had fully indirect effects on cognitive function, mediated by the WMHs. Conclusions This study suggests that WMHs may play a vital mediating role in the relationship between inflammation, oxidative stress, and cognitive impairments in SCH. Future studies exploring the potential clinical utility of WMHs as biomarkers for early detection and intervention of SCH are warranted. |
| format | Article |
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| institution | OA Journals |
| issn | 1471-244X |
| language | English |
| publishDate | 2025-05-01 |
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| series | BMC Psychiatry |
| spelling | doaj-art-d106e3ee262b404e8fce31afcc52ee542025-08-20T02:15:05ZengBMCBMC Psychiatry1471-244X2025-05-012511810.1186/s12888-025-06905-1White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional studyYan Zhang0Xiuxia Yuan1Yu Zhang2Yishao Chen3Keju Su4Kangkang Xue5Suying Ding6Jingfeng Chen7Xiaoduo Fan8Xueqin Song9Department of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou UniversityHealth Management Center, The First Affiliated Hospital of Zhengzhou UniversityHealth Management Center, The First Affiliated Hospital of Zhengzhou UniversityPsychotic Disorders Program, UMass Memorial Medical Center, University of Massachusetts Medical SchoolDepartment of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Studies have reported that white matter hyperintensities (WMHs) are associated with disturbances in immune function, and the relationship between WMHs and cognitive impairments have been documented in various clinical populations. The present study was to examine the relationship between WMHs, immune function, and cognitive impairments in patients with schizophrenia (SCH) remains unknown. Methods A sample of 127 drug-naïve first episode SCH and 72 healthy controls (HCs) were included in this study. Serum levels of cytokines and oxidative stress indices were measured using enzyme-linked immunosorbent assay and microtiter plate method. WMHs were assessed using T2-weighted magnetic resonance imaging scanning, and cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery. Results We found patients with SCH are more likely to present with WMHs compared with HCs (OR = 2.076, 95%CI 1.007–4.277, p = 0.048). SCH with WMHs displayed more pronounced cognitive deficits in domains including speed of processing, working memory, verbal learning, visual learning, reasoning, and problem-solving compared with patients without WMHs (p < 0.05). Correlation analysis showed that the volume of WMHs was negative correlated with the problem-solving score (r=-0.331, p = 0.042) in patients with SCH. Within the SCH group, patients with WMHs exhibited elevated levels of interleukin-2 (IL-2), reactive oxygen species (ROS), and superoxide dismutase (SOD), along with lower levels of serum interleukin-4 (IL-4) and interferon-γ (IFN-γ) compared with those without WMHs (p < 0.05). The mediation analyses demonstrated that serum levels of IFN-γ in SCH had fully indirect effects on cognitive function, mediated by the WMHs. Conclusions This study suggests that WMHs may play a vital mediating role in the relationship between inflammation, oxidative stress, and cognitive impairments in SCH. Future studies exploring the potential clinical utility of WMHs as biomarkers for early detection and intervention of SCH are warranted.https://doi.org/10.1186/s12888-025-06905-1SchizophreniaCognitive impairmentsWhite matter hyperintensitiesInflammationOxidative stress indices |
| spellingShingle | Yan Zhang Xiuxia Yuan Yu Zhang Yishao Chen Keju Su Kangkang Xue Suying Ding Jingfeng Chen Xiaoduo Fan Xueqin Song White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study BMC Psychiatry Schizophrenia Cognitive impairments White matter hyperintensities Inflammation Oxidative stress indices |
| title | White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study |
| title_full | White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study |
| title_fullStr | White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study |
| title_full_unstemmed | White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study |
| title_short | White matter hyperintensities, inflammation and cognitive impairments in drug-naïve first episode schizophrenia patients: a cross-sectional study |
| title_sort | white matter hyperintensities inflammation and cognitive impairments in drug naive first episode schizophrenia patients a cross sectional study |
| topic | Schizophrenia Cognitive impairments White matter hyperintensities Inflammation Oxidative stress indices |
| url | https://doi.org/10.1186/s12888-025-06905-1 |
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