Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA.
Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL 32306, USA.
Exp Biol Med (Maywood). 2021 May;246(9):1084-1093. doi: 10.1177/1535370221991830. Epub 2021 Feb 16.
Major depressive disorder (MDD or depression) is a debilitating neuropsychiatric syndrome with genetic, epigenetic, and environmental contributions. Depression is one of the largest contributors to chronic disease burden; it affects more than one in six individuals in the United States. A wide array of cellular and molecular modifications distributed across a variety of neuronal processes and circuits underlie the pathophysiology of depression-no established mechanism can explain all aspects of the disease. MDD suffers from a vast treatment gap worldwide, and large numbers of individuals who require treatment do not receive adequate care. This mini-review focuses on dysregulation of brain dopamine (DA) systems in the pathophysiology of MDD and describing new cellular targets for potential medication development focused on DA-modulated micro-circuits. We also explore how neurodevelopmental factors may modify risk for later emergence of MDD, possibly through dopaminergic substrates in the brain.
重度抑郁症（MDD 或抑郁症）是一种具有遗传、表观遗传和环境因素的使人衰弱的神经精神综合征。抑郁症是导致慢性疾病负担的最大因素之一；它影响了美国六分之一以上的人。抑郁症的病理生理学基础是广泛分布于各种神经元过程和回路中的多种细胞和分子改变，没有一种既定的机制可以解释该疾病的所有方面。MDD 在全球范围内存在巨大的治疗差距，大量需要治疗的人没有得到足够的护理。这篇迷你评论聚焦于 MDD 病理生理学中大脑多巴胺（DA）系统的失调，并描述了新的细胞靶点，这些靶点可能针对以 DA 调节的微电路为重点的潜在药物开发。我们还探讨了神经发育因素如何通过大脑中的多巴胺能基质来改变以后出现 MDD 的风险。
