Epigenetics involves molecular mechanisms related to gene expression independent of DNA sequence, mostly mediated by modification of chromatin histones. It has recently been suggested that these transcriptional changes may be implicated in the pathophysiology of mood disorders. In addition, histone deacetylase (HDAC) inhibitors have been shown to control epigenetic programming associated with the regulation of cognition and behavior, and may reverse dysfunctional epigenetic regulation associated with early life events in preclinical models. In this context, the active and continuous adaptation of chromatin, and the access of gene promoters to transcription factor mechanisms may represent a potential therapeutic target in the treatment of mood disorders such as bipolar disorder (BD) and major depressive disorder (MDD). Notably, the standard mood stabilizer valproate (VPA) has been shown to modulate the epigenome by inhibiting HDACs. However, several potential limitations are associated with this class of agents, including lack of selectivity for specific HDAC isoforms as well as risk of potentially serious side effects. Further studies regarding the potential role of chromatin remodeling in the mechanism of action of antidepressants and mood stabilizers are necessary to clarify the potential role of this class of agents as therapeutics for mood disorders.

中文翻译：

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组蛋白去乙酰化酶和情绪障碍：基因-环境相互作用中的表观遗传编程。

表观遗传学涉及与独立于 DNA 序列的基因表达相关的分子机制，主要由染色质组蛋白的修饰介导。最近有人提出，这些转录变化可能与情绪障碍的病理生理学有关。此外，组蛋白去乙酰化酶 (HDAC) 抑制剂已被证明可以控制与认知和行为调节相关的表观遗传编程，并可能逆转临床前模型中与早期生活事件相关的表观遗传调节功能障碍。在这种情况下，染色质的主动和持续适应以及基因启动子对转录因子机制的访问可能代表治疗双相情感障碍 (BD) 和重度抑郁症 (MDD) 等情绪障碍的潜在治疗目标。尤其，标准情绪稳定剂丙戊酸盐 (VPA) 已被证明可通过抑制 HDAC 来调节表观基因组。然而，这类药物存在一些潜在的局限性，包括缺乏对特定 HDAC 同种型的选择性以及潜在严重副作用的风险。有必要进一步研究染色质重塑在抗抑郁药和情绪稳定剂的作用机制中的潜在作用，以阐明此类药物作为情绪障碍治疗剂的潜在作用。