Hypersexual disorder (HD) defined as non-paraphilic sexual desire disorder with components of impulsivity, compulsivity and behavioral addiction, was proposed as a diagnosis in the DSM-5. Recent research shows some overlapping features between HD and substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. We have reported that HD was significantly associated to DST non-suppression and higher plasma DST-ACTH levels indicating HPA axis dysregulation in male patients with HD.

In this cohort, comprising 54 male patients diagnosed with HD and 33 healthy male volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality.

We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality in 87 male subjects, adjusting for depression, DST non-suppression status, CTQ total score, and plasma levels of TNF-alpha and IL-6.

Seventy-six individual CpG sites were tested, and four of these were nominally significant (P < 0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074–located 48 bp upstream of the TSS of the CRH gene–was significantly hypomethylated in hypersexual patients after corrections were made for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. CRH is an important integrator of neuroendocrine stress responses in the brain, modulating behavior and the autonomic nervous system; our results show epigenetic changes in CRH gene related to hypersexual disorder in men.

The author has not supplied his/her declaration of competing interest.