When sex starts to negatively interfere with one’s life, getting in the way of essentials like relationships, careers, and personal care, some experts say that person could be dealing with compulsive sexual behavior disorder, also sometimes known as hypersexual disorder (HD). It’s a controversial matter: Others argue it’s not something that can even be diagnosed, despite the fact that it is classified by the World Health Organization as an impulse disorder.

Adding to this mix is a study published Sunday in the journal Epigenetics, which reveals a potential genetic basis for the understudied disorder. In this study, scientists pinpoint two regions of DNA that are altered in people who have been diagnosed with HD.

In this population’s genes, a process called DNA methylation was disrupted, while an associated microRNA was under-expressed. This molecule group, known as microRNA-4456, is the same microRNA that’s dysregulated in alcohol-dependent populations.

The study authors claim these findings could lead to novel treatment options. Currently, the conventional treatment for HD is group administered cognitive behavioral therapy.

“While prevalence estimates vary, literature indicates that hypersexual disorder affects three to six percent of the population,” lead author, Adrian Bostrom, M.D. and Ph.D. candidate in the department of neuroscience at Uppsala University, Sweden, tells Inverse. “However, controversy surrounds the diagnosis and little is known about the neurobiology behind it.”

Other sexual behavior experts warn that the study’s findings are limited, possibly even overreaching. Nicole Prause, Ph.D., a neuroscientist who studies human sexual behavior, tells Inverse that suggesting that that uncontrollable sexual behavior can be explained by genes is a stretch.

How compulsive sexual behavior is listed in the ICD-11. WHO

In the study, the researchers compared 60 participants with HD with 33 healthy volunteers. They also examined samples of 107 subjects, 24 of whom were alcohol-dependent, to investigate an association with addictive behavior. The team used computer algorithms to analyze over 8,000 DNA methylation sequences in the blood of the study’s participants.

DNA methylation is an epigenetic mechanism which cells use to control gene expression. Here, the researchers found the DNA methylation process in individuals diagnosed with HD was disrupted, while the individual’s microRNA-4456, which also affects gene silencing, was under-expressed.

DNA methylation and microRNAs both help turn genes into the “lock” position. But if their mechanisms are disrupted, there can be less gene silencing. With less gene silencing, other hormonal processes are knocked out of whack. This team speculates that this can result in elevated oxytocin levels, but currently can’t confirm this.

Oxytocin, the so-called “love hormone,” plays a critical role in social and pair bonding, sexual reproduction, and aggression. When we hug, cuddle, have sex, or have babies, oxytocin is released, building trust and attachment. But if oxytocin levels are off-balanced, impulsivity, as well as addictive and aggressive behavior can result.

The researchers also compared participants with HD to those with alcoholism.

“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,” Bostrom explains.

However, Prause stresses that multiple bodies have agreed sex is not addictive.

“Suggesting a single methylation difference resembled in an atypical ‘alcoholic’ sample means sex is addictive is a gross overreach of these data,” Prause tells Inverse.

Is sex addictive?

The science of sex is mixed, and there’s little consensus on the exact prevalence of HD or whether sex can be considered an “addiction.”

It was not included in the latest edition of the Diagnostic and Statistical Manual (DSM-5), the holy grail of psychiatric diagnoses published in 2013 by the American Psychiatric Association. But compulsive sexual behavior disorder, also known as HD, was classified in 2018 as an impulse control disorder in the International Classification of Diseases (ICD-11), a diagnostic manual published by the World Health Organization (WHO). The ICD describes HD as: “a persistent pattern of failure to control intense, repetitive sexual impulses or urges resulting in repetitive sexual behavior.”

But Prause cautions that the ICD’s inclusion of compulsive sexual behavior disorder is misguided. She says the diagnosis as written was never tested and is not used in the United States. Any country that plans to implement the ICD-11, must wait until January 1, 2022.

“The ICD also added ‘homosexuality’ after the DSM had removed it, so the World Health Organization has a history of pathologizing normal sexual behaviors,” Prause says.

The study authors do note that the mean difference in DNA methylation between hypersexual disorder patients and healthy volunteers was only 2.6 percent, a relatively subtle difference. But they say some research has shown that even small changes in methylation may have big impacts: on conditions like depression and schizophrenia.

More research is needed to further investigate the exact connection between DNA methylation, oxytocin, and hypersexual disorder. This could eventually lead to further formalizing the diagnosis and developing pharmacological treatments for HD — or if these biological factors aren’t established, it can show that issues linked to sex are a manifestation of another problem.

Abstract:

Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ‘Compulsive Sexual Behavior Disorder’ is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome-wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD – cg18222192 (MIR708)(p < 10E-05, pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes 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. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signaling.