Epigenetic Study Finds Overactive Hormone May Drive Hypersexual Disorder

Sex is a natural and normal part of life. When practiced safely with a consenting partner, it’s not only pleasurable but has certain health benefits. However, some people can be obsessed with sex, to the point that it causes them more harm than does any good. These individuals are usually diagnosed with having hypersexual disorder (HSD) – a condition where excessive sexual thoughts and actions interfere with the ability to function day-to-day.

Often accompanied by other medical conditions, the causes of HSD are not fully understood. Now, new research is shedding light on the neurobiology behind this disorder. For the first time, scientists are connecting oxytocin, the “love hormone,” epigenetically to the development of HSD. Their results were recently published in the journal of Epigenetics.

HSD, which has also been referred to as sex addiction, is a compulsive sexual behavior disorder. Listed by the World Health Organization as an ICD-11 mental health disorder, it affects approximately 3 – 6% of the population. People who meet the criteria for HSD have a preoccupation with sexual thoughts, urges, and behaviors that are difficult to control. They frequently use sex to cope with stress and are compelled to conduct their sexual habits despite any negative consequences that may arise.

Previous studies have shown that epigenetics plays an important role in the pathophysiology of many psychiatric diseases, including bipolar disorder, major depressive disorder, and post-traumatic stress disorder. Shifts in epigenetic patterns can influence the functioning of the central nervous system, and these modifications have been found to affect sexual behavior in animal models significantly.

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Because no other study has examined HSD with regards to epigenomics and transcriptomics, the researchers here decided to compare DNA methylation patterns of HSD patients to healthy volunteers.

According to lead author Adrian Boström of Uppsala University, Sweden, this study may be the first to connect dysregulated DNA methylation and microRNA activity to oxytocin in the brain of people diagnosed with HSD.

“We set out to investigate the epigenetic regulatory mechanisms behind hypersexual disorder,” he said, “so we could determine whether it has any hallmarks that make it distinct from other health issues.”

The team analyzed 8,852 miRNA-associated CpG-sites found in the blood of 60 HSD patients and compared them to 33 healthy subjects. Their aim was to identify any variations in DNA methylation patterns between the samples.

Changes in DNA methylation can alter gene expression, resulting in reduced gene activity. In areas where DNA methylation was detected, the researchers looked to see if micro RNA activity was affected. These fine-regulatory genes are of notable interest because they can cross the blood-brain barrier and transform the expression of numerous different proteins, many of which are involved in the progression of various mental disorders.

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The researchers furthered their investigation by comparing their findings to samples taken from alcohol-dependent individuals to determine if there was an association with addictive behavior.

The results from the study identified two regions of DNA that were altered in HSD patients. In these regions, DNA methylation was irregular, and microRNAs associated with gene silencing were found to exhibit lower expression. One microRNA detected, mRNA-4456, targets highly expressed genes in the brain that regulate the hormone oxytocin. If gene silencing diminishes in this region, oxytocin levels would then subsequently increase.

In animal studies, oxytocin has demonstrated to play a role in pair-bonding behavior. It has also been associated with sexual reproduction and aggressive behavior in humans. Moreover, this same region of the DNA was found in this study to be under-methylated in subjects with alcohol dependence. Thus, suggesting an addictive element may be affecting HSD.

“Further research will be needed to investigate the role of microRNA-4456 and oxytocin in hypersexual disorder, said professor Jussi Jokinen from Umeå University, Sweden, who worked on the study. “Our results suggest it could be worthwhile to examine the benefits of drug and psychotherapy to reduce the activity of oxytocin.”

One noted limitation of the study was that only a slight difference in DNA methylation was detected between HSD and healthy participants (around 2.6%). This small difference is questionable, which is why further studies should be done to validate these results. However, subtle changes in methylation can have a wide range of consequences. Evidence has been reported in several studies to date concerning depression and schizophrenia.

Current treatments for HSD tend to mimic methods used in other addictive or compulsive-type personality disorders. Yet, there’s a delicacy to controlling behavior that should not entirely be extinguished. Sex has a purpose, and it should be part of a healthy lifestyle. Hopefully, research like this will eventually lead to treatments that suppress the neural activity involved in this condition and allow those struggling with HSD to regain a normal sex life. 

Source: Boström, Adrian E. 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 Sep 22:1-16.

Reference: September 23, 2019, “Scientists identify hormone potentially linked to hypersexual disorder.” Taylor & Francis Group Newsroom.

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