Ralph H. Johnson Veterans Affairs Health Care System, Charleston, SC, USA.
Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, USA.
Mol Psychiatry. 2023 Jan;28(1):298-328. doi: 10.1038/s41380-022-01819-w. Epub 2022 Oct 17.
Globally, depression is a leading cause of disability and has remained so for decades. Antidepressant medications have suboptimal outcomes and are too frequently associated with side effects, highlighting the need for alternative treatment options. Although primarily known for its robust physical health benefits, exercise is increasingly recognized for its mental health and antidepressant benefits. Empirical evidence indicates that exercise is effective in treating individuals with depression; however, the mechanisms by which exercise exerts anti-depressant effects are not fully understood. Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immuno-inflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been demonstrated to consistently modulate such mechanisms, and evidence linking these putative mechanisms and reductions in depression is lacking. The complexity of the biological underpinnings of depression coupled with the intricate molecular cascade induced by exercise are significant obstacles in the attempt to disentangle exercise's effects on depression. Notwithstanding our limited understanding of these effects, clinical evidence uniformly argues for the use of exercise to treat depression. Regrettably, exercise remains underutilized despite being an accessible, low-cost alternative/adjunctive intervention that can simultaneously reduce depression and improve overall health. To address the gaps in our understanding of the clinical and molecular effects of exercise on depression, we propose a model that leverages systems biology and multidisciplinary team science with a large-scale public health investment. Until the science matches the scale of complexity and burden posed by depression, our ability to advance knowledge and treatment will continue to be plagued by fragmented, irreproducible mechanistic findings and no guidelines for standards of care.
在全球范围内，抑郁症是导致残疾的主要原因，几十年来一直如此。抗抑郁药物的疗效并不理想，而且常常伴有副作用，这凸显了需要替代治疗方案。尽管运动主要以其对身体健康的强大益处而闻名，但它对心理健康和抗抑郁的益处也越来越受到认可。实证证据表明，运动对治疗抑郁症患者有效；然而，运动发挥抗抑郁作用的机制尚未完全理解。急性运动已被证明可短暂调节抑郁患者循环中的血清素和去甲肾上腺素、脑源性神经营养因子和多种免疫炎症机制的水平。然而，运动训练并没有被证明能持续调节这些机制，也没有证据表明这些推测的机制与抑郁症的减少有关。抑郁症的生物学基础的复杂性，加上运动引起的复杂分子级联，是在试图阐明运动对抑郁症的影响方面的重大障碍。尽管我们对这些影响的了解有限，但临床证据一致认为应使用运动来治疗抑郁症。遗憾的是，尽管运动是一种可及且低成本的替代/辅助干预措施，可以同时减轻抑郁和改善整体健康，但它的使用仍然不足。为了解决我们对运动对抑郁症的临床和分子影响的理解差距，我们提出了一个利用系统生物学和多学科团队科学以及大规模公共卫生投资的模型。在科学与抑郁症的复杂性和负担相匹配之前，我们推进知识和治疗的能力将继续受到零散、不可复制的机制发现和缺乏护理标准指南的困扰。
