23 Sep Epigenetic Changes Linked to Hypersexual Disorder and Addictive Behaviors

MedicalResearch.com Interview with:
Adrian E. Boström MD, on behalf of the authors
Department of Neuroscience
Uppsala University, Sweden 

MedicalResearch.com: What is the background for this study?

Response: While prevalence estimates vary, literature indicates that hypersexual disorder (HD) affects 3-6% of the population. However, controversy surrounds the diagnosis and little is known about the neurobiology behind it.

Hypersexual disorder has not previously been investigated with regards to epigenomic and transcriptomics in a hypothesis-free study approach and little is known about the neurobiology behind this disorder. We investigated whether there were any epigenetic changes that affect gene activity and expression in hypersexual disorder (HD) patients and identified a dysregulated microRNA that is believed to influence the mechanism of action of the hormone oxytocin in brain.

Oxytocin is known to have wide-ranging behavioral influences. To the best of our knowledge, no previous study provided evidence for an association between DNA methylation, microRNA activity and oxytocin in hypersexual disorder. Our findings merits further research in the role of MIR4456 and especially Oxytocin in hypersexual disorder. Further studies are needed to confirm the role of Oxytocin in HD and to investigate whether treatment with oxytocin antagonist drug therapy could have beneficial effects for patients suffering from hypersexual disorder. 

MedicalResearch.com: What are the main findings?

Response: – In this study we investigated over 8000 different DNA methylation sequenced in a hypothesis-free and thereby unbiased manner. Therefore, we were intrigued and surprised to identify a strongly dysregulated microRNA targeting genes primarily expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for hypersexual disorder, e.g. the oxytocin signaling pathway. This microRNA also appears to be evolutionary conserved throughout primates, which is also an interesting and unexpected finding. 

MedicalResearch.com: What should readers take away from your report?

Response: Hypersexual disorder incorporates different pathophysiological mechanisms including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. This can be interpreted such that hypersexual disorder contains addictive elements, but is not to be seen as exclusively an addiction. Our findings, in light of the crossover with alcohol dependence, suggest that MIR4456 and the oxytocin signaling pathway may be primarily involved with the addictive component of hypersexual disorder. Further studies are needed to fully confirm this.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Our results motivates further research in the efficacy of, for example, oxytocin regulating drug therapy in hypersexual disorder which could contribute to novel treatment options to improve the clinical outcome of those affected. In addition, we identify a specific microRNA (miRNA) for which future potential miRNA regulating drugs could be tested in hypersexual disorder. 

MedicalResearch.com: Is there anything else you would like to add?

Response: Our DNA is genetic code for genes that translate into different sequences of amino acids called proteins. Proteins, in turn, constitute a main defining element of all living things. Our DNA is inherited and does not change over time. This study, however, pertained to epigenetics, which are changes that affect gene activity and expression. These epigenetic activities change over time and can be dysregulated in certain ailments. There are different epigenetic mechanisms.

In this study, we studied DNA methylation (a process known to influence gene expression, that is, the quantity of a gene that is translated into a protein)  and microRNA activity (short non-coding gene segments that can influence the translation of several hundred different genes).

Comparing patients with hypersexual disorder to healthy volunteers, we identified a DNA methylation sequence to be significantly altered in hypersexual disorder. To ascertain the significance of this finding, the same DNA sequence was further demonstrated to be dysregulated in subjects with alcohol dependence, suggesting it could be primarily associated with the addictive component of hypersexual disorder. The identified DNA methylation sequence was associated to a microRNA called (microRNA 4456; MIR4456), and further analysis showed that this DNA methylation sequence influence the quantity of MIR4456 that is produced. Furthermore, in the same study group, we demonstrate that MIR4456 exists in significantly lower quantity in hypersexual disorder as compared to healthy volunteers, strongly suggesting that altered DNA methylation patterns in hypersexual disorder influence and contributes to explaining the observed dysregulation of MIR4456. As microRNA:s theoretically are able to target several hundred different genes, we used computer algorithms to reveal that MIR4456 targets genes that are preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signaling pathway. Our findings merits further research in the role of MIR4456 and especially Oxytocin in hypersexual disorder. Further studies are needed to confirm the role of Oxytocin in HD and to investigate whether treatment with oxytocin antagonist drug therapy could have beneficial effects for patients suffering from hypersexual disorder.

Yet unpublished data intended for a separate follow-up study show a highly significant increase in Oxytocin levels in patients with hypersexual disorder as compared to controls, and a significant reduction in oxytocin levels after Cognitive Behavior Therapy treatment, strongly implying a causal role of Oxytocin in hypersexual disorder and making the claims presented in this study much stronger. These preliminary results have been presented as a late breaking poster in Society of Biological Psychiatry meeting in May 2019 and also submitted as a poster in ACNP in December 2019.

Citation:

Adrian E. Boström et al, Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes, Epigenetics (2019). DOI: 10.1080/15592294.2019.1656157

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Last Updated on September 23, 2019 by Marie Benz MD FAAD