Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Genes (Basel). 2020 Sep 18;11(9):1089. doi: 10.3390/genes11091089.
Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field.
尽管近几十年来进行了广泛的研究，但重度抑郁症（MDD）的分子机制和相关循证治疗仍不清楚。已经提出了各种假设，涉及不同的生物系统。本叙述性综述旨在批判性地说明 MDD 的主要发病假说，从基于单胺能和神经营养理论的历史假说开始，到随后的神经发育、谷氨酸能、GABA 能、炎症/免疫和内分泌解释，直到最近提出脂肪酸和肠道微生物群起作用的证据。此外，还回顾了已确立的 MDD 药物和非药物治疗方法的分子作用。总的来说，现有文献表明，这些不同假说背景下描述的分子机制，而不是相互替代的机制，很可能共同作用，通常相互影响，导致 MDD 的发生和治疗的有效性，并指出需要在这一领域进一步努力研究。
