Bortolato Beatrice, Carvalho Andre F, Soczynska Joanna K, Perini Giulia I, McIntyre Roger S
Department of Psychiatry and Pharmacology, University of Toronto, Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, ON, Canada M5T2S8.
Curr Neuropharmacol. 2015;13(5):558-76. doi: 10.2174/1570159x13666150630171433.
Major depressive disorder is a highly prevalent, chronic and recurring disorder, associated with substantial impairment in cognitive and interpersonal functions. Accumulating evidence suggests that inflammatory processes play an important role in the etio-pathogenesis, phenomenology, comorbidity and treatment of MDD. Suboptimal remission rates and the persistence of cognitive deficits contribute to functional impairment in MDD inviting the need for the development of mechanistically novel and domain specific treatment approaches. The MEDLINE/ Pubmed database was searched from inception to February, 9th, 2014 with combinations of the following search terms: 'TNF-alpha', 'depression', 'infliximab', 'etanercept', 'adalimumab', 'golimumab' and 'certolizumab'. Preclinical and clinical evidence linking TNF-α to MDD pathophysiology were reviewed as well as the current status of TNF-α modulators as novel agents for the treatment of MDD. Experimental models and clinical studies provide encouraging preliminary evidence for the efficacy of TNF- α antagonists in mitigating depressive symptoms and improving cognitive deficits. Further studies are warranted to confirm these data in larger randomized controlled trials in primary psychiatric populations. Translational research provides a promising perspective that may aid the development and/or repurposing of mechanism-based treatments for depressive symptoms and cognitive impairment in MDD.
重度抑郁症是一种高度流行、慢性且复发性的疾病，与认知和人际功能的严重损害相关。越来越多的证据表明，炎症过程在重度抑郁症的病因发病机制、临床表现、共病情况及治疗中发挥着重要作用。缓解率欠佳以及认知缺陷的持续存在导致了重度抑郁症患者的功能损害，因此需要开发新的、具有特定作用机制的治疗方法。对MEDLINE/Pubmed数据库从创建至2014年2月9日进行检索，使用了以下检索词的组合：“肿瘤坏死因子-α”、“抑郁症”、“英夫利昔单抗”、“依那西普”、“阿达木单抗”、“戈利木单抗”和“赛妥珠单抗”。回顾了将肿瘤坏死因子-α与重度抑郁症病理生理学联系起来的临床前和临床证据，以及肿瘤坏死因子-α调节剂作为治疗重度抑郁症新药的现状。实验模型和临床研究为肿瘤坏死因子-α拮抗剂减轻抑郁症状和改善认知缺陷的疗效提供了令人鼓舞的初步证据。有必要进行进一步研究，在更大规模的原发性精神疾病人群随机对照试验中证实这些数据。转化研究提供了一个有前景的视角，可能有助于开发和/或重新利用针对重度抑郁症患者抑郁症状和认知障碍的基于机制的治疗方法。
