Pizzagalli Diego A
Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478; email:
Annu Rev Clin Psychol. 2014;10:393-423. doi: 10.1146/annurev-clinpsy-050212-185606.
Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (a) anhedonia, (b) dopamine, and (c) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affects mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reinforcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research.
抑郁症是一个重大的公共卫生问题，但其病因和病理生理学仍知之甚少。这种认识不全面可能源于抑郁症包含一系列异质性疾病这一事实。为克服这些局限性，人们对中间表型（内表型）重新产生了兴趣，快感缺失已成为抑郁症最有前景的内表型之一。在此，我们提出一个启发式模型，假定快感缺失源于应激与大脑奖赏系统之间的功能失调性相互作用。为此，我们回顾并整合了三组独立文献，这些文献分别研究了（a）快感缺失、（b）多巴胺和（c）应激在抑郁症中的作用。在第四部分，我们总结了动物实验数据，这些数据表明应激会对中脑边缘多巴胺能通路产生负面影响，而该通路在动机激励和强化学习中起着关键作用。在最后一部分，我们综合了这四组文献，呈现了与我们模型一致的初步证据，并讨论了未来的研究方向。
