Methylation of the HPA axis related genes in men with hypersexual disorder

• Background and aims: Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, was proposed as a diagnosis in the DSM 5. Some overlapping features between HD and substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function have been reported. In this study, comprising 67 male patients diagnosed with HD and 39 healthy male volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. Methods: The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850 K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000 bp of the transcriptional start site of the following HPAaxis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, DST non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Results: 76 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 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. Conclusions: 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Publication and Content Type

ref (subject category)

art (subject category)