Serotonin system-associated genetic and epigenetic changes in pedophilia and child sexual offending

Numerous studies have shown associations between anomalies of the serotonergic system and impulsive behavior, depression, or traumatic life events. However, it is currently unknown, whether pedophilia or child sexual offending (CSO) is also related to alterations of the serotonergic system. Using a two by two factorial paradigm within a multisite consortium (NeMUP*) study cohort, we analyzed whether the SLC6A4-linked polymorphic region (SLC6A4LPR) or the SLC6A4 (transporter) and HTR3A (receptor) promotor methylation rates differed with regard to a pedophilic preference and/or child sexual offending. Methylation rates of HTR3A showed significant differences between child sexual offenders and non-offenders, with child sexual offenders showing lower methylation rates. Moreover, HTR3A methylation rates showed significant negative correlations with the Child Trauma Questionnaire (CTQ) subscale "sexual violence", and the number of sexual offenses committed. Interestingly, we also found pedophilia-related alterations in 5HT_3A as well as SLC6A4 methylation rates. For HTR3A we detected significant higher methylation rates in subjects with a pedophilic sexual preference, whereas for SLC6A4 methylation rates were reduced, indicating a possible downregulation of the serotonergic system in total. Although there were no significant group differences concerning the SLC6A4LPR, we found a significant correlation of the SLC6A4 methylation rate with this polymorphism in pedophilia. The present study suggests an involvement of epigenetic alterations of the serotonergic system in pedophilia and child sexual offending as well as own experience of sexual violence. While such an environmental factor may account for the epigenetic changes seen in child sexual offending, this was not seen in pedophilia. These findings will hopefully inspire further research in this underinvestigated field which should aim at validating and extending these initial results.