Department of Psychology, Concordia University, Montreal, QC, Canada.
CHU Sainte-Justine Hospital Research Center, Montreal, QC, Canada.
Mol Psychiatry. 2019 Oct;24(10):1425-1434. doi: 10.1038/s41380-019-0366-8. Epub 2019 Feb 11.
Anorexia nervosa (AN) and other eating disorders continue to constitute significant challenges for individual and public health. AN is thought to develop as a result of complex interactions between environmental triggers, psychological risk factors, sociocultural influences, and genetic vulnerability. Recent research developments have highlighted a novel potentially relevant component in the AN etiology-activity of the histone deacetylase 4 (HDAC4) gene that has emerged in several recent studies related to AN. HDAC4 is a member of the ubiquitously important family of epigenetic modifier enzymes called histone deacetylases and has been implicated in processes related to the formation and function of the central nervous system (CNS), bone, muscle, and metabolism. In a family affected by eating disorders, a missense mutation in HDAC4 (A786T) was found to segregate with the illness. The relevance of this mutation in eating-related behaviors was further confirmed with mouse models. Despite the fact that HDAC4 has not been identified as a significant signal in genome-wide association studies in AN, several studies have found significant or near-significant methylation differences in HDAC4 locus in peripheral tissues of actively ill AN patients in comparison with different control groups. Limitations of these studies include a lack of understanding of to what extent the changes in methylation are predictive of AN as such changes might also occur as a consequence of the disease. It remains to be determined how methylation in peripheral tissues correlates with that in the CNS and how different methylation patterns affect HDAC4 expression. The present review discusses the findings and potential roles of HDAC4 in AN. Its emerging roles in learning and neuroplasticity may be specific and relevant for the etiology of AN and potentially lead to novel therapeutic approaches.
神经性厌食症 (AN) 和其他饮食失调症继续对个人和公共健康构成重大挑战。AN 被认为是由于环境触发因素、心理风险因素、社会文化影响和遗传易感性之间的复杂相互作用而发展起来的。最近的研究进展强调了 AN 病因学中的一个新的潜在相关因素——组蛋白去乙酰化酶 4 (HDAC4) 基因的活性，该基因在与 AN 相关的几项最近的研究中出现。HDAC4 是一种普遍存在的表观遗传修饰酶家族的成员，称为组蛋白去乙酰化酶，它与中枢神经系统 (CNS)、骨骼、肌肉和代谢的形成和功能有关。在一个受饮食失调症影响的家庭中，发现 HDAC4 中的错义突变 (A786T) 与该疾病分离。该突变与饮食相关行为的相关性进一步通过小鼠模型得到证实。尽管在 AN 的全基因组关联研究中未发现 HDAC4 是一个重要信号，但几项研究发现，与不同对照组相比，活跃的 AN 患者外周组织中的 HDAC4 基因座存在显著或接近显著的甲基化差异。这些研究的局限性包括缺乏对甲基化变化在多大程度上预测 AN 的理解，因为这种变化也可能是疾病的结果。目前尚不清楚外周组织中的甲基化与 CNS 中的甲基化如何相关，以及不同的甲基化模式如何影响 HDAC4 的表达。本综述讨论了 HDAC4 在 AN 中的发现和潜在作用。其在学习和神经可塑性方面的新兴作用可能是特定的，与 AN 的病因学相关，并有潜力导致新的治疗方法。
