Department of Psychiatry and Behavioral Sciences, University of Texas Dell Medical School in Austin, and Mulva Clinic for the Neurosciences, UT Health Austin.
Am J Psychiatry. 2020 Aug 1;177(8):671-685. doi: 10.1176/appi.ajp.2020.20060845.
Major depressive disorder is a remarkably common and often severe psychiatric disorder associated with high levels of morbidity and mortality. Patients with major depression are prone to several comorbid psychiatric conditions, including posttraumatic stress disorder, anxiety disorders, obsessive-compulsive disorder, and substance use disorders, and medical conditions, including cardiovascular disease, diabetes, stroke, cancer, which, coupled with the risk of suicide, result in a shortened life expectancy. The goal of this review is to provide an overview of our current understanding of major depression, from pathophysiology to treatment. In spite of decades of research, relatively little is known about its pathogenesis, other than that risk is largely defined by a combination of ill-defined genetic and environmental factors. Although we know that female sex, a history of childhood maltreatment, and family history as well as more recent stressors are risk factors, precisely how these environmental influences interact with genetic vulnerability remains obscure. In recent years, considerable advances have been made in beginning to understand the genetic substrates that underlie disease vulnerability, and the interaction of genes, early-life adversity, and the epigenome in influencing gene expression is now being intensively studied. The role of inflammation and other immune system dysfunction in the pathogenesis of major depression is also being intensively investigated. Brain imaging studies have provided a firmer understanding of the circuitry involved in major depression, providing potential new therapeutic targets. Despite a broad armamentarium for major depression, including antidepressants, evidence-based psychotherapies, nonpharmacological somatic treatments, and a host of augmentation strategies, a sizable percentage of patients remain nonresponsive or poorly responsive to available treatments. Investigational agents with novel mechanisms of action are under active study. Personalized medicine in psychiatry provides the hope of escape from the current standard trial-and-error approach to treatment, moving to a more refined method that augurs a new era for patients and clinicians alike.
重度抑郁症是一种非常常见且通常严重的精神障碍，与高发病率和死亡率相关。患有重度抑郁症的患者容易出现几种合并的精神疾病，包括创伤后应激障碍、焦虑症、强迫症和物质使用障碍，以及包括心血管疾病、糖尿病、中风、癌症在内的躯体疾病，这些疾病加上自杀风险，导致预期寿命缩短。本综述的目的是提供对重度抑郁症的全面了解，从病理生理学到治疗。尽管经过了几十年的研究，但除了风险主要由定义不明确的遗传和环境因素的组合来定义之外，对于其发病机制，我们知之甚少。尽管我们知道女性、童年虐待史和家族史以及最近的压力源是风险因素，但这些环境影响如何与遗传易感性相互作用仍然不清楚。近年来，在开始理解疾病易感性的遗传基础方面取得了相当大的进展，并且基因、早期生活逆境和表观基因组在影响基因表达方面的相互作用正在得到深入研究。炎症和其他免疫系统功能障碍在重度抑郁症发病机制中的作用也在被深入研究。脑成像研究为重度抑郁症涉及的回路提供了更坚实的理解，为潜在的新治疗靶点提供了依据。尽管有广泛的治疗重度抑郁症的方法，包括抗抑郁药、循证心理疗法、非药物躯体治疗和许多增效策略，但仍有相当大比例的患者对现有治疗方法无反应或反应不佳。具有新作用机制的研究性药物正在积极研究中。精神科的个体化医学提供了从目前的标准试错治疗方法中摆脱出来的希望，转向一种更精细的方法，为患者和临床医生带来了一个新时代。
