Molecular Biological Aspects of Depressive Disorders: A Modern View
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Molecular Biological Aspects of Depressive Disorders: A Modern View V. M. Ushakovaa, b, *, A. Yu. Morozovaa, d, A. M. Reznikc, G. P. Kostyukd, and V. P. Chekhonina, e aSerbsky
National Medical Research Center of Psychiatry and Narcology, Moscow, 119034 Russia bMoscow State University, Moscow, 119234 Russia c Moscow State University of Food Production, Moscow, 125080 Russia dAlekseev Psychiatric Clinical Hospital no. 1, Moscow, 117152 Russia e Pirogov Russian National Research Medical University, Moscow, 117997 Russia *e-mail: [email protected] Received April 21, 2020; revised May 15, 2020; accepted May 16, 2020
Abstract—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. Keywords: depression pathogenesis, schizophrenia, bipolar disorder, neurodegeneration, monoamines, BDNF, neuroinflammation, epigenetics, CRISPR/Cas, optogenetics DOI: 10.1134/S0026893320050118
INTRODUCTION Depressive disorders affect almost 350 million people [1] and dramatically impair the working ability and life quality of patients. Depressive symptoms often accompany other mental and neurological disorders. For example, 40–60% of schizophrenic patients have depressive symptoms [2, 3] and neurodegenerative diseases, such as Parkinson (PD) and Alzheimer’s (AD) diseases, are associated with affective disorders in 30– 50% of cases [4]. Thus, the term “depression” includes a broad range of pathological conditions [5].
Depression is a complex heterogeneous disorder of the brain and is underlain by a set of biochemical, molecular genetic, and anatomical alterations. The available data associate affective pathology with dysfunction of monoaminergic systems of the brain, impairment of the hypothalamic–pituitary–adrenal (HPA) system, a lower production of brain trophic factors, and distorted neuroplasticity [6].
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