Abstract:
: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.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Sild M,Booij Ldoi
10.1038/s41380-019-0366-8subject
Has Abstractpub_date
2019-10-01 00:00:00pages
1425-1434issue
10eissn
1359-4184issn
1476-5578pii
10.1038/s41380-019-0366-8journal_volume
24pub_type
杂志文章,评审abstract::Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like ...
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