Pan Zihang, Rosenblat Joshua D, Swardfager Walter, McIntyre Roger S
Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street - Toronto, ON, Canada.
Hurvitz Brain Science Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Curr Pharm Des. 2017;23(14):2065-2072. doi: 10.2174/1381612823666170111144340.
Anhedonia, characterized by a loss of interest and/or pleasure in previously enjoyable activities, is an important diagnostic criterion of Major Depressive Disorder (MDD). Converging evidence implicates a causal relationship between proinflammatory cytokines and behavioural disturbances that characterize anhedonia in the context of MDD. Additionally, anhedonia has been implicated in disturbances of key central dopaminergic modulatory pathways. Emerging research into the roles of tetrahydrobiopterin, a cytokine-targeted co-enzyme in the synthesis of dopamine, and kynurenine, a product of inflammation-sensitive breakdown of tryptophan via indoleamine 2, 3-dioxygenase, have shed new light into the role of inflammation in mediating anhedonic behaviours. The following narrative review is not meant to be comprehensive, but highlights the roles of both tetrahydrobiopterin and kynurenine pathways in anhedonia, and discusses a potential mechanism of action via oxidative stress and excitotoxicity. Treatment implications are discussed, with an emphasis on anti-inflammatories as complements to current treatments of anhedonia and MDD.
快感缺失，其特征是对以前喜欢的活动失去兴趣和/或愉悦感，是重度抑郁症（MDD）的一项重要诊断标准。越来越多的证据表明，促炎细胞因子与MDD背景下以快感缺失为特征的行为障碍之间存在因果关系。此外，快感缺失还与关键的中枢多巴胺能调节通路紊乱有关。对四氢生物蝶呤（一种多巴胺合成中细胞因子靶向的辅酶）和犬尿氨酸（色氨酸经吲哚胺2,3-双加氧酶进行炎症敏感分解的产物）作用的新研究，为炎症在介导快感缺失行为中的作用提供了新的线索。以下叙述性综述并非全面综述，而是强调了四氢生物蝶呤和犬尿氨酸通路在快感缺失中的作用，并讨论了通过氧化应激和兴奋性毒性的潜在作用机制。文中还讨论了治疗意义，重点是抗炎药物作为当前快感缺失和MDD治疗补充的作用。
