Slavich George M, Irwin Michael R
Cousins Center for Psychoneuroimmunology, University of California, Los Angeles.
Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302. Epub 2014 Jan 13.
Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.
重大生活应激源，尤其是那些涉及人际压力和社会排斥的应激源，是抑郁症最强的近端风险因素之一。在本综述中，我们提出了一个具有生物学合理性的多层次理论，该理论描述了将社会环境应激体验与驱动抑郁症发病机制的内部生物学过程联系起来的神经、生理、分子和基因组机制。抑郁症的这种社会信号转导理论的核心假说是，社会威胁和逆境体验会上调参与炎症反应的免疫系统成分。这种反应的关键介质，即促炎细胞因子，反过来又会引发行为上的深刻变化，包括引发抑郁症状，如情绪低落、快感缺失、疲劳、精神运动迟缓以及社交行为退缩。这种对逆境高度保守的生物学反应在实际身体威胁或受伤时对生存至关重要。然而，这种反应也可能被现代社会、象征性或想象中的威胁激活，导致炎症表型日益增加，这可能是驱动抑郁症发病机制和复发的关键现象，也是抑郁症与包括哮喘、类风湿性关节炎、慢性疼痛、代谢综合征、心血管疾病、肥胖症和神经退行性变在内的几种躯体疾病重叠的原因。因此，该理论的见解可能会阐明几个重要问题，包括抑郁症如何发展、为何频繁复发、为何早年生活应激能强烈预测抑郁症以及为何它常与焦虑症状和某些躯体疾病症状同时出现。这项工作还可能通过针对炎症反应为预防和治疗抑郁症提供新的机会。
