Chronic or repeated social stress exposure often precipitates the onset of depression and cardiovascular disease (CVD). Despite a clear clinical association between CVD and depression, the pathophysiology underlying these comorbid conditions is unclear. Chronic exposure to social stress can lead to immune system dysregulation, mitochondrial dysfunction, and vagal withdrawal. Further, regular physical exercise is well-known to exert cardioprotective effects, and accumulating evidence demonstrates the antidepressant effect of exercise. This review explores the contribution of inflammation, mitochondrial dysfunction, and vagal withdrawal to stress-induced depression and CVD. Evidence for therapeutic benefits of exercise, anti-inflammatory therapies, and vagus nerve stimulation are also reviewed. Benefits of targeted therapeutics of mitochondrial agents, anti-inflammatory therapies, and vagus nerve stimulation are discussed. Importantly, the ability of exercise to impact each of these factors is also reviewed. The current findings described here implicate a new direction for research, targeting the shared mechanisms underlying comorbid depression-CVD. This will guide the development of novel therapeutic strategies for the prevention and treatment of these stress-related pathologies, particularly within treatment-resistant populations.

长期或反复的社会压力暴露通常会导致抑郁症和心血管疾病 (CVD) 的发作。尽管 CVD 和抑郁症之间存在明确的临床关联，但这些共存疾病的病理生理学尚不清楚。长期暴露于社会压力会导致免疫系统失调、线粒体功能障碍和迷走神经退缩。此外，众所周知，定期体育锻炼可以发挥心脏保护作用，并且越来越多的证据表明锻炼具有抗抑郁作用。这篇综述探讨了炎症、线粒体功能障碍和迷走神经退缩对压力诱发的抑郁症和 CVD 的影响。还审查了运动、抗炎疗法和迷走神经刺激的治疗益处的证据。讨论了线粒体药物靶向治疗、抗炎治疗和迷走神经刺激的益处。重要的是，还审查了运动影响这些因素中的每一个的能力。这里描述的当前发现暗示了一个新的研究方向，针对共病抑郁症-CVD 的共同机制。这将指导开发新的治疗策略，以预防和治疗这些与压力相关的病理，特别是在抗药人群中。