Neuroimmune Mechanisms of Mood Disorder: A Translational Perspective

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 role 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 role 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.