Lamontagne Steven J, Ballard Elizabeth D, Zarate Carlos A
Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Neurobiol Stress. 2022 Apr 20;18:100450. doi: 10.1016/j.ynstr.2022.100450. eCollection 2022 May.
Suicide is a leading cause of death and morbidity worldwide, yet few interventions are available to mitigate its risk. Barriers to effective treatments involve a limited understanding of factors that predict the onset of suicidal thoughts and behaviors. In the context of suicide risk, stress is a precipitating factor that is largely overlooked in the literature. Indeed, the pathophysiology of stress and suicide are heavily interconnected, underscoring the need to target the stress system in suicide prevention. In this review, we integrate findings from the preclinical and clinical literature that links stress and suicide. We focus specifically on the effects of stress on underlying biological functions and processes associated with suicide, allowing for the review of research using animal models. Owing to the rapid anti-suicidal effects of ()-ketamine, we discuss its ability to modulate various stress-related endophenotypes of suicide, as well as its potential role in preventing suicide in those with a history of chronic life stress (e.g., early life adversity). We highlight future research directions that could advance our understanding of stress-related effects on suicide risk, advocating a dimensional, endophenotype approach to suicide research.
自杀是全球死亡和发病的主要原因之一，但降低自杀风险的干预措施却很少。有效治疗的障碍包括对预测自杀念头和行为发生的因素了解有限。在自杀风险方面，压力是一个在文献中很大程度上被忽视的促发因素。事实上，压力和自杀的病理生理学紧密相连，这凸显了在预防自杀中针对压力系统的必要性。在这篇综述中，我们整合了临床前和临床文献中关于压力与自杀关联的研究结果。我们特别关注压力对与自杀相关的潜在生物学功能和过程的影响，从而能够对使用动物模型的研究进行综述。由于（）-氯胺酮具有快速的抗自杀作用，我们讨论了它调节自杀各种与压力相关的内表型的能力，以及它在预防有慢性生活压力史（如早年逆境）的人自杀方面的潜在作用。我们强调了未来的研究方向，这些方向可能会增进我们对压力相关因素对自杀风险影响的理解，倡导采用维度、内表型方法进行自杀研究。
