Neuroimmune Mechanisms of Mood Disorder: A Translational Perspective

情緒疾病之神經免疫反應：轉譯醫學觀點

陳柏熹(Po-See Chen)

《台灣精神醫學》 29卷4期 (2015/12) Pp. 227-237+78

摘要

各種牽涉到人際關係的社會壓力是情緒疾病最強烈相關的危險因子。 在本綜論中將嘗試以生物基礎，在不同層次連結個人在經驗社會壓力後個體內與情緒疾病發生相關之神經免疫機制。此神經免疫機制之核心包含免疫系統—腦雙向互動以及其對情緒及行為之影響。在社會壓力情境下，交感神經系統會增強周邊髓細胞生成，單核細胞轉移，以及與對逆境的保守轉錄反應中相關發炎因子的基因表達。進而增高的發炎細胞激素將會誘發腦中微膠細胞活化以及周邊單核細胞轉移致腦中，影響情緒行為進而表現出無歡樂感，激躁，精神運動遲滯以及社交行為畏縮等表現。因為以高敏感度方法決定的Ｃ反應蛋白濃度是現今醫學研究中最廣泛被研究與使用的發炎因子，因此在本文中將以轉譯醫學的角度，以Ｃ反應蛋白為例來回顧神經發炎反應在情緒疾病中所扮演的角色。文中回顧周邊血液中Ｃ反應蛋白濃度與情緒疾病個案情緒狀態及其治療反應間的相關性。之後並整理過去曾使用抗發炎藥物作為情緒疾病治療輔助治療之臨床試驗結果。最後作者提出神經發炎相關機轉可能是情緒疾病中多系統生理性共病以及晚年增加失智症風險的共同機制。藉文中相關研究增進我們對情緒疾病中免疫系統—腦雙向互動機制，心理社會壓力的角色，生理多系統共病，以及晚期認知功能變化的瞭解。最後，這些情緒疾病中神經免疫反應的知識，將有機會幫助我們以發炎反應為焦點來預防並治療情緒疾病。

關鍵字

社會逆境 ； Ｃ反應蛋白 ； 神經免疫反應 ； 情緒疾病

並列摘要

Psychosocial adverse conditions involving interpersonal processes are among the strongest proximal risk factors for mood disorders. In this overview, I propose a biologically plausible, multilevel theory that link experiences of social adverse condition with internal neuroimmune mechanisms that drive pathogenesis for mood disorders. Central to this neuroimmune mechanism hypothesis is a novel axis of immune-to-brain bidirectional communication that infl uences mood and behavior. Under social adverse conditions, sympathetic nervous system and hypothalamic– pituitary adrenal axis can up-regulate myelopoiesis, monocyte traffi cking and the expression of pro-infl ammatory genes encoding a conserved transcriptional response to adversity (CTRA). Then elevated pro-infl ammatory cytokines caused by central microglia activation and recruitment of monocytes to the brain contribute to development of mood symptoms such as anhedonia, aggression, psychomotor retardation and social-behavioral withdrawal. Because C-reactive protein (CRP) determined by high-sensitivity methods currently is the most extensively studied infl ammatory biomarker, therefore, this article provides a comprehensive review of current knowledge concerning the current rôle of CRP in neuroimmune mechanisms of mood disorders from a translational perspective. The author suggests that the serum CRP levels is to be used as a biomarker for mood statuses and a predictor of treatment response in mood disorders. The author will also review the data of the clinical trials that used anti-infl ammatory medications as adjunct pharmacotherapy in treating mood disorders. Finally, the author concludes that the neuroimmune mechanisms might link mood disorders with multiple system co-morbidities and sequential dementing change. Insights from this theory may thus shed light on understanding of immune-to-brain bidirectional communications, the rôle of psychosocial adverse conditions, the neuroimmune mechanisms of co-morbidities and late life consequence in mood disorders. Knowledge of the neuroimmune mechanisms may provide opportunities for preventing and treating mood disorders by targeting infl ammation.

並列關鍵字

social adverse condition ； C-reactive protein ； neuroimmune mechanism ； mood disorder