CRC, Rm 30, 57 Laurel Street, Glasgow, G11 7QT, Scotland.
CNS Drugs. 2014 Jan;28(1):1-10. doi: 10.1007/s40263-013-0119-1.
Accumulating data have led to a re-conceptualization of depression that emphasizes the role of immune-inflammatory processes, coupled to oxidative and nitrosative stress (O&NS). These in turn drive the production of neuroregulatory tryptophan catabolites (TRYCATs), driving tryptophan away from serotonin, melatonin, and N-acetylserotonin production, and contributing to central dysregulation. This revised perspective better encompasses the diverse range of biological changes occurring in depression and in doing so provides novel and readily attainable treatment targets, as well as potential screening investigations prior to treatment initiation. We briefly review the role that immune-inflammatory, O&NS, and TRYCAT pathways play in the etiology, course, and treatment of depression. We then discuss the pharmacological treatment implications arising from this, including the potentiation of currently available antidepressants by the adjunctive use of immune- and O&NS-targeted therapies. The use of such a frame of reference and the treatment benefits attained are likely to have wider implications and utility for depression-associated conditions, including the neuroinflammatory and (neuro)degenerative disorders.
越来越多的数据使得人们重新认识到抑郁症的发病机制，强调了免疫炎症过程、氧化应激和硝化应激（O&NS）的作用。这些反过来又会导致神经调节色氨酸分解代谢产物（TRYCATs）的产生，从而使色氨酸远离血清素、褪黑素和 N-乙酰血清素的产生，并导致中枢失调。这种修正后的观点更好地包含了抑郁症中发生的各种生物学变化，并为新的、易于实现的治疗靶点提供了依据，以及在开始治疗前进行潜在的筛查调查。我们简要回顾了免疫炎症、O&NS 和 TRYCAT 途径在抑郁症的病因、病程和治疗中的作用。然后，我们讨论了由此产生的药理学治疗意义，包括通过联合使用免疫和 O&NS 靶向治疗来增强现有的抗抑郁药。这种参考框架的使用和所获得的治疗益处可能对与抑郁症相关的疾病（包括神经炎症和（神经）退行性疾病）具有更广泛的意义和实用性。
