Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: Further evidence for disease course-related immune alterations?

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• 作者：Stefan Busse ; M ; y Busse ; Kolja Schiltz ; Hendrik Bielau ; Tomasz Gos ; Ralf Brisch ; Christian Mawrin ; Andrea Schmitt ; Wolfgang Jordan ; Ulf J. M¨¹ller ; Hans-Gert Bernstein ; Bernhard Bogerts ; Johann Steiner
• 关键词：Schizophrenia ; Blood&ndash ; brain barrier ; Microglia ; HLA-DR ; Lymphocytes ; CD3 ; CD20 ; Hippocampus
• 刊名：Brain, Behavior, and Immunity
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：26
• 期：8
• 页码：1273-1279
• 全文大小：492 K

文摘

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain¡¯s mononuclear phagocyte system (microglial cells) is activated during acute psychosis.

Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n = 7) and paranoid (prominent positive symptoms, n = 10) schizophrenia cases.

Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P = 0.047, right: P = 0.038; CD20: left: P = 0.020, right: P = 0.010) and controls (CD3: left: P = 0.057, right: P = 0.069; CD20: left: P = 0.008, right: P = 0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P = 0.030, right: P = 0.012). A similar trend emerged when this group was compared to controls (left: P = 0.090, right: P = 0.090).

BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.