Rosenblat Joshua D, McIntyre Roger S
Department of Psychiatry, University of Toronto, Toronto, ON M5T 2S8, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON M5T 2S8, Canada.
Brain Sci. 2017 Oct 30;7(11):144. doi: 10.3390/brainsci7110144.
Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA) axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a of BD patients and as such, future clinical trials should also strive to identify which specific group(s) of BD patients may benefit from anti-inflammatory treatments.
双相情感障碍（BD）与免疫功能障碍密切相关。多项重复的流行病学研究表明，BD患者合并炎症性疾病的比例很高，包括自身免疫性疾病、慢性感染、心血管疾病和代谢紊乱。细胞因子研究表明，BD与慢性低度炎症有关，在情绪发作期间促炎细胞因子水平会进一步升高。已确定了几种机制来解释BD与免疫功能障碍之间的双向关系。关键机制包括细胞因子诱导的单胺变化、氧化应激增加、病理性小胶质细胞过度激活、下丘脑-垂体-肾上腺（HPA）轴过度激活、微生物群-肠道-脑轴改变以及与睡眠相关的免疫变化。炎症-情绪通路为BD的治疗提供了几个潜在的新靶点。几项概念验证临床试验表明，抗炎药物在BD治疗中具有积极作用；然而，需要进一步研究以确定这些治疗方法的临床实用性。免疫功能障碍可能仅在一部分BD患者中起作用，因此，未来的临床试验还应努力确定哪些特定组别的BD患者可能从抗炎治疗中获益。
