Epigenetic alterations of serotonergic but not dopaminergic signalling in compulsive sexual behaviour disorder

The compulsive sexual behaviour disorder (CSBD) is a recent addition to the ICD-11 diagnostic manual under the chapter of impulse control disorders. Though there is a wealth of different theoretical viewpoints regarding the nature of CSBD, which highlight aspects such as compulsivity, impulsivity, behavioural addiction, and emotional dysregulation to differing degrees, the empirical support is currently lacking. In this study we were exploring the hypothesis of increased sexual excitation and/or decreased sexual inhibition, as represented by overactive dopaminergic and hypoactive serotonergic signalling, respectively, by means of examining methylation status of various dopaminergic and serotonergic genes.

This study investigated the involvement of epigenetic mechanisms in compulsive sexual behaviour disorder (CSBD), by studying methylation patterns of selected dopaminergic and serotonergic genes.

We examined methylation rates of selected dopaminergic and serotonergic targets, by bisulfite conversion of the DNA extracted from blood samples of thirty six healthy controls and forty three CSBD individuals. Our targets included genes DRD2 (dopamine receptor type 2), SLC6A3/DAT (dopamine transporter), HTR3A (serotonin receptor 3 A) and SLC6A4/5HTT (serotonin transporter). Furthermore we analysed correlation of epigenetic markers with sexual outlet variables and selected questionnaires.

Analysis revealed significantly higher methylation of the 5HTT/SLC6A4 (serotonin transporter gene), suggesting reduced central expression of the serotonin transporter in the CSBD individuals. Group differences in 5HT3A receptor gene methylation were non-significant; however, the threshold of significance reached was suggestive of a potential effect. Larger sample size and increased statistical power would be needed to provide stronger statistical evidence. These findings were further supported by correlations between the methylation status of these two serotonergic genes and sexual outlet indicators in the control group. Importantly, no such association was observed in CSBD patients, which may suggest a lack of epigenetic regulatory feedback, potentially leading to suboptimal signalling of sexual drive and satiety. Notably, no epigenetic differences were observed for dopaminergic targets (DRD2 receptor gene and DAT/SLC6A3 transporter gene).

Overall, these findings suggest that dysregulation of serotonergic signalling might contribute to the CSBD etiology and further exploration of this avenue with larger sample sizes might be beneficial to our understanding of compulsive sexuality. We found no evidence of epigenetic dysregulation in dopaminergic target genes. The lack of association of methylation rates and sexual outlet in CSBD individuals is indicative of the lack of epigenetic regulatory feedback, hence of potentially abnormal signalling of sexual drive and satiety.