Irwin Michael R
Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, at University of California, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Biol Psychiatry. 2025 May 4. doi: 10.1016/j.biopsych.2025.04.018.
Insomnia is ubiquitous, co-morbid with all major mental disorders, increases the risk of depression, and contributes to inflammatory morbidity and all-cause mortality. This review examines the relationships between insomnia and inflammation in the pathophysiology of depression. The unique role of insomnia on depression risk is examined with interrogation of what aspects of sleep disturbance contribute to depressed mood. Further, the influence of insomnia, as well as specific its specific aspects (i.e., short sleep duration, disturbance of sleep maintenance) on affective mechanisms are considered, with a focus on reward activation and emotion processing. Given that inflammation contributes to some types of depression, the bidirectional interactions between sleep and inflammation are examined with consideration of how sleep deprivation induces activation of systemic, cellular, and genomic inflammatory outcomes, and the causal role of inflammation in precipitating depressed mood and depressive symptoms. Key gaps in the literature linking insomnia and inflammation to depression risk are identified, and maps for future research are proposed. Specifically, this review considers how the components of insomnia and inflammation conspire together to exaggerate deficits in reward activation and recognition of emotion, which underlie depression risk and adverse depression outcomes. Finally, informed by this two-hit model of insomnia and inflammation on depression risk, this review examines the efficacy of behavioral interventions that target insomnia and reverse related inflammation, and discusses their potential to refine therapeutic approaches for depression treatment and prevention in persons with insomnia.
失眠普遍存在，与所有主要精神障碍共病，增加抑郁风险，并导致炎症性疾病和全因死亡率上升。本综述探讨了失眠与炎症在抑郁症病理生理学中的关系。通过审视睡眠障碍的哪些方面导致情绪低落，来研究失眠对抑郁风险的独特作用。此外，还考虑了失眠及其特定方面（即睡眠时间短、睡眠维持障碍）对情感机制的影响，重点关注奖赏激活和情绪处理。鉴于炎症会导致某些类型的抑郁症，本文探讨了睡眠与炎症之间的双向相互作用，考虑了睡眠剥夺如何诱导全身、细胞和基因组炎症反应的激活，以及炎症在引发情绪低落和抑郁症状中的因果作用。确定了将失眠和炎症与抑郁风险联系起来的文献中的关键空白，并提出了未来研究的路线图。具体而言，本综述探讨了失眠和炎症的成分如何共同作用，加剧奖赏激活和情绪识别方面的缺陷，而这些缺陷是抑郁风险和不良抑郁结局的基础。最后，基于这种失眠和炎症对抑郁风险的双重打击模型，本综述研究了针对失眠并逆转相关炎症反应的行为干预措施的疗效，并讨论了它们在改进失眠患者抑郁症治疗和预防治疗方法方面的潜力。
