Song Chen1, Li Tian2, Nan Chen3, Mei-Hong Xiu3, Zhi-Ren Wang3, Yue-Chan Wang3, Yun-Long Tan4, Chuan-Yue Wang5. 1. The National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing HuiLongGuan Hospital, Peking University, Beijing, China. 2. Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Biomedicine and Translational Medicine, Department of Physiology, Faculty of Medicine, University of Tartu, Estonia; Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland. 3. Beijing HuiLongGuan Hospital, Peking University, Beijing, China. 4. Beijing HuiLongGuan Hospital, Peking University, Beijing, China. Electronic address: yltan21@126.com. 5. The National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. Electronic address: wang_cy@ccmu.edu.cn.
Abstract
OBJECTIVE: Accumulating evidence suggests alterations of the innate immune system are related to schizophrenia, although the precise mechanism remains to be elucidated. In this study, we aimed to detect the monocytic toll-like receptor 4 (TLR4) expression under basal and lipopolysaccharide (LPS)-stimulated conditions in first-episode (FE) Han Chinese patients with schizophrenia, as well as its association with cognitive function. METHODS: Whole blood samples were taken in 42 FE schizophrenia patients and 36 healthy controls. Expressions of TLR4 on monocytes under basal and LPS-stimulated conditions were measured with flow cytometry. Psychopathological symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) was administered to all of the participants. RESULTS: We found no differences in percentage and mean fluorescence intensity (MFI) of TLR4 expression on monocytes between patients and controls at basal status. However, LPS challenge resulted in a lower cell-surface level of TLR4 on monocytes in FE schizophrenia patients as compared to healthy controls (TLR4+%: F = 4.092, p = 0.047; TLR4 + MFI: F = 4.820, p = 0.031). In addition, correlation analysis together with multivariate linear regression analysis identified basal percentage of TLR4 in monocytes as the beneficial factor for visual learning and working memory in FE patients with schizophrenia. CONCLUSIONS: Our findings suggested that TLR4 may be involved in the pathophysiology of schizophrenia, corroborating the role of innate immunity-related functional deficits in increased risk of schizophrenia.
OBJECTIVE: Accumulating evidence suggests alterations of the innate immune system are related to schizophrenia, although the precise mechanism remains to be elucidated. In this study, we aimed to detect the monocytic toll-like receptor 4 (TLR4) expression under basal and lipopolysaccharide (LPS)-stimulated conditions in first-episode (FE) Han Chinese patients with schizophrenia, as well as its association with cognitive function. METHODS: Whole blood samples were taken in 42 FE schizophreniapatients and 36 healthy controls. Expressions of TLR4 on monocytes under basal and LPS-stimulated conditions were measured with flow cytometry. Psychopathological symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) was administered to all of the participants. RESULTS: We found no differences in percentage and mean fluorescence intensity (MFI) of TLR4 expression on monocytes between patients and controls at basal status. However, LPS challenge resulted in a lower cell-surface level of TLR4 on monocytes in FE schizophreniapatients as compared to healthy controls (TLR4+%: F = 4.092, p = 0.047; TLR4 + MFI: F = 4.820, p = 0.031). In addition, correlation analysis together with multivariate linear regression analysis identified basal percentage of TLR4 in monocytes as the beneficial factor for visual learning and working memory in FE patients with schizophrenia. CONCLUSIONS: Our findings suggested that TLR4 may be involved in the pathophysiology of schizophrenia, corroborating the role of innate immunity-related functional deficits in increased risk of schizophrenia.