Subramaniapillai Mehala, Carmona Nicole E, Rong Carola, McIntyre Roger S
Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada ; Department of Pharmacology, University of Toronto, Toronto, Canada.
Dialogues Clin Neurosci. 2017 Mar;19(1):27-36. doi: 10.31887/DCNS.2017.19.1/rmcintyre.
Mood disorders continue to be a significant burden to those affected, resulting in significant illness-associated disability and premature mortality. In addition to mood disturbance, individuals also suffer from other transdiagnostic impairments (eg, anhedonia and cognitive impairment). Although there have been significant advancements in psychiatric treatment over the last few decades, treatment efficacy (eg, symptom remission, lack of functional recovery, and disease modification) continues to be an important limitation. Consequently, there is an urgent need to identify novel approaches capable of addressing the foregoing needs, providing the basis for the exploration of conceptual models and treatment opportunities that consider inflammation to be a key factor in mood disorder development. In part driven by metabolic comorbidities, a large proportion of individuals with mood disorders also have an imbalance in the inflammatory milieu. The aim of this review is to highlight evidence implicating inflammation in various effector systems in mood disorders, with a particular focus on the intercommunication with glutamatergic signaling, immune system signaling, as well as metabolic parameters (eg, L-methyl folate bioavailability). This article also briefly reviews novel and repurposed agents that are capable of targeting the innate immune inflammatory system and possibly correcting an abnormal immune/inflammatory milieu (eg, infliximab).
情绪障碍仍然是患者的重大负担,会导致严重的疾病相关残疾和过早死亡。除了情绪紊乱外,患者还患有其他跨诊断性损伤(如快感缺失和认知障碍)。尽管在过去几十年里精神科治疗取得了重大进展,但治疗效果(如症状缓解、功能恢复不佳和疾病改善)仍然是一个重要的限制因素。因此,迫切需要找到能够满足上述需求的新方法,为探索将炎症视为情绪障碍发展关键因素的概念模型和治疗机会提供依据。部分受代谢合并症的驱动,很大一部分情绪障碍患者还存在炎症环境失衡的情况。本综述的目的是强调炎症与情绪障碍中各种效应系统相关的证据,特别关注与谷氨酸能信号传导、免疫系统信号传导以及代谢参数(如L-甲基叶酸生物利用度)的相互作用。本文还简要回顾了能够靶向先天性免疫炎症系统并可能纠正异常免疫/炎症环境的新型和重新利用的药物(如英夫利昔单抗)。