Ushakova V M, Morozova A Yu, Reznik A M, Kostyuk G P, Chekhonin V P
Serbsky National Medical Research Center of Psychiatry and Narcology, Moscow, 119034 Russia.
Moscow State University, Moscow, 119234 Russia.
Mol Biol (Mosk). 2020 Sep-Oct;54(5):725-749. doi: 10.31857/S0026898420050110.
Depression is a serious mental disorder that affects more than 300 million people worldwide. Due to the lack of effective treatment methods, the pathogenesis of depression is necessary to study in order to understand its development and find new therapies. The review describes the main mechanisms of depression, including the monoamine hypothesis, impairment of the hipotalamic-pituitary-adrenal axis, decreased production of neurotropic factors, and neuroinflammation. Genetic correlations, gene polymorphisms, and epigenetic mechanisms are also considered. Common and different features of the etiology are analyzed for depression and depressive conditions associated with other pathologies (schizophrenia, Parkinson disease, and Alzheimer's disease). Modern experimental methods used to investigate the molecular mechanisms of depressive conditions are described with a focus on gene knockouts in laboratory animals and the CRISPR/Cas technology. Consideration is given to optogenetic and chemogenetic methods and analyses of genetic polymorphisms and their combinations. The data may provide for a better integral understanding of the modern ideas about the pathogenesis of depression as an isolated or comorbid disorder and the prospects in studying the mechanisms of depressive conditions.
抑郁症是一种严重的精神障碍，全球有超过3亿人受其影响。由于缺乏有效的治疗方法，有必要研究抑郁症的发病机制，以便了解其发展过程并找到新的治疗方法。这篇综述描述了抑郁症的主要机制，包括单胺假说、下丘脑 - 垂体 - 肾上腺轴功能受损、神经营养因子产生减少以及神经炎症。还考虑了遗传相关性、基因多态性和表观遗传机制。分析了抑郁症以及与其他病理状况（精神分裂症、帕金森病和阿尔茨海默病）相关的抑郁状态在病因学上的共同和不同特征。描述了用于研究抑郁状态分子机制的现代实验方法，重点是实验室动物中的基因敲除和CRISPR/Cas技术。还考虑了光遗传学和化学遗传学方法以及基因多态性及其组合的分析。这些数据可能有助于更好地整体理解关于抑郁症作为一种独立或共病障碍的发病机制的现代观点以及研究抑郁状态机制的前景。
