Advances in characterizing molecular profiles provide valuable insights and opportunities for deciphering the neuropathology of depression. Although abnormal brain‐derived neurotrophic factor (BDNF) expression in depression has gained much support from preclinical and clinical research, how it mediates behavioral alterations in the depressed state remains largely obscure. Environmental factors contribute significantly to the onset of depression and produce robust epigenetic changes. Epigenetic regulation of BDNF, as one of the most characterized gene loci in epigenetics, has recently emerged as a target in research on memory and psychiatric disorders. Specifically, epigenetic alterations of BDNF exons are heavily involved in mediating memory functions and antidepressant effects. In this review, we discuss key research on stress‐induced depression from both preclinical and clinical studies, which revealed that differential epigenetic regulation of specific BDNF exons is associated with depression pathophysiology. Considering that BDNF has a central role in depression, we argue that memory extinction, an adaptive response to fear exposure, is dependent on BDNF modulation and holds promise as a prospective target for alleviating or treating depression and anxiety disorders.

中文翻译：

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脑源性神经营养因子表观遗传学的新见解：从抑郁症到记忆力消退

表征分子谱的进展为破译抑郁症的神经病理学提供了宝贵的见解和机会。尽管抑郁症中异常的脑源性神经营养因子 (BDNF) 表达得到了临床前和临床研究的大量支持，但它如何介导抑郁状态下的行为改变仍然很大程度上不清楚。环境因素对抑郁症的发作有显着影响，并产生强烈的表观遗传变化。BDNF 的表观遗传调控作为表观遗传学中最具特征的基因位点之一，最近已成为记忆和精神疾病研究的一个目标。具体而言，BDNF 外显子的表观遗传改变与调节记忆功能和抗抑郁作用密切相关。在这次审查中，我们讨论了临床前和临床研究中关于压力诱发的抑郁症的关键研究，这些研究表明特定 BDNF 外显子的差异表观遗传调控与抑郁症病理生理学有关。考虑到 BDNF 在抑郁症中发挥核心作用，我们认为记忆消退是对恐惧暴露的适应性反应，依赖于 BDNF 调节，并有望成为缓解或治疗抑郁症和焦虑症的预期目标。