Blokhin Ilya O, Khorkova Olga, Saveanu Radu V, Wahlestedt Claes
Center for Therapeutic Innovation, University of Miami, Miami, FL, United States of America; Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, United States of America; Jackson Memorial Hospital, Miami, FL, United States of America.
OPKO Health Inc., Miami, FL, United States of America.
Neurobiol Dis. 2020 Dec;146:105136. doi: 10.1016/j.nbd.2020.105136. Epub 2020 Oct 17.
For most psychiatric diseases, pathogenetic concepts as well as paradigms underlying neuropsychopharmacologic approaches currently revolve around neurotransmitters such as dopamine, serotonin, and norepinephrine. However, despite the fact that several generations of neurotransmitter-based psychotropics including atypical antipsychotics, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors are available, the effectiveness of these medications is limited, and relapse rates in psychiatric diseases are relatively high, indicating potential involvement of other pathogenetic pathways. Indeed, recent high-throughput studies in genetics and molecular biology have shown that pathogenesis of major psychiatric illnesses involves hundreds of genes and numerous pathways via such fundamental processes as DNA methylation, transcription, and splicing. Current review summarizes these and other molecular mechanisms of such psychiatric illnesses as schizophrenia, major depressive disorder, and alcohol use disorder and suggests a conceptual framework for future studies.
对于大多数精神疾病而言,目前神经精神药理学方法背后的发病机制概念及范式均围绕多巴胺、血清素和去甲肾上腺素等神经递质展开。然而,尽管已有几代基于神经递质的精神药物,包括非典型抗精神病药物、选择性血清素再摄取抑制剂以及血清素 - 去甲肾上腺素再摄取抑制剂,但这些药物的疗效有限,精神疾病的复发率相对较高,这表明其他发病途径可能也参与其中。事实上,近期遗传学和分子生物学的高通量研究表明,主要精神疾病的发病机制涉及数百个基因以及通过DNA甲基化、转录和剪接等基本过程的众多途径。本综述总结了精神分裂症、重度抑郁症和酒精使用障碍等精神疾病的这些及其他分子机制,并为未来研究提出了一个概念框架。