Watkins C C, Sawa A, Pomper M G
Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore, MD, USA.
1] Department of Psychiatry and Behavioral Sciences, John Hopkins University School of Medicine, Baltimore, MD, USA [2] Division of Neuroradiology, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transl Psychiatry. 2014 Jan 21;4(1):e350. doi: 10.1038/tp.2013.119.
Bipolar disorder (BD) is a debilitating mental illness characterized by severe fluctuations in mood, sleep, energy and executive functioning. Pharmacological studies of selective serotonin reuptake inhibitors and the monoamine system have helped us to clinically understand bipolar depression. Mood stabilizers such as lithium and valproic acid, the first-line treatments for bipolar mania and depression, inhibit glycogen synthase kinase-3 beta (GSK-3β) and regulate the Wnt pathway. Recent investigations suggest that microglia, the resident immune cells of the brain, provide a physiological link between the serotonin system and the GSK-3β/Wnt pathway through neuroinflammation. We review the pharmacological, translational and brain imaging studies that support a role for microglia in regulating neurotransmitter synthesis and immune cell activation. These investigations provide a model for microglia involvement in the pathophysiology and phenotype of BD that may translate into improved therapies.
双相情感障碍（BD）是一种使人衰弱的精神疾病，其特征是情绪、睡眠、精力和执行功能出现严重波动。选择性5-羟色胺再摄取抑制剂和单胺系统的药理学研究有助于我们从临床上理解双相抑郁。诸如锂盐和丙戊酸等心境稳定剂，作为双相躁狂和抑郁的一线治疗药物，可抑制糖原合酶激酶-3β（GSK-3β）并调节Wnt信号通路。最近的研究表明，小胶质细胞作为大脑中的常驻免疫细胞，通过神经炎症在5-羟色胺系统与GSK-3β/Wnt信号通路之间建立了生理联系。我们综述了支持小胶质细胞在调节神经递质合成和免疫细胞激活中发挥作用的药理学、转化医学和脑成像研究。这些研究为小胶质细胞参与双相情感障碍的病理生理学和表型提供了一个模型，这可能会转化为更好的治疗方法。
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