THE HTR1B-rs13212041-T/T GENOTYPE AS A POTENTIAL BIOLOGICAL CORRELATE OF PSYCHOPATHY

Background: Psychopathy is a condition characterized by atypical emotions and socially maladaptive behavioral patterns affecting about 25% of institutionalized males. Among criminal offenders, psychopathy has been associated with higher rates of crimes, recidivism and resistance to treatment. Many studies have indicated significant heritability of psychopathic traits, but little is known about the specific contribution of genes and their interaction with adverse experiences in life. Methods: Considering the primary role that serotonin plays in cognition and emotion, we investigated TPH2-rs4570625 (in the gene coding for the serotonin synthetizing enzyme), 5-HTTLPR (in the gene coding for the serotonin transporter), MAOA-uVNTR (in the gene coding for the monoamine metabolizing enzyme), HTR1B-rs13212041 (in the gene coding for the serotonin auto receptor 1B) and HTR2A-rs6314 (in the gene coding for the serotonin receptor 2A) as risk factors for psychopathy, in the largest sample of institutionalized males studied to date, consisting of 793 US White incarcerated adults, and in a replication sample of 168 US White male incarcerated adolescents. In a subgroup of the adult sample, the interaction between genetics and parenting style, assessed by the Measure of Parental Style (MOPS) questionnaire, was also evaluated. Results: The HTR1B-rs13212041-T/T genotype, as compared to HTR1B-rs13212041-C allele, predicted higher Psychopathy scores in both the adult and the adolescent samples. The interaction between HTR1B-rs13212041-T/T genotype and paternal MOPS scores, investigated only in the adult sample, was an even stronger predictor of higher levels of psychopathy than either the genetic or the environmental factor taken individually. Discussion: As the T allele of HTR1B-rs13212041 allows for the interaction with a regulatory microRNA (i.e., miR-96) enabling a miRNA-mediated reduction of HTR1B gene expression and previous findings showed that childhood adversities induce hyper-methylation and reduce the expression of the serotonin receptor 1B, we hypothesize that paternal maltreatment lead to epigenetic changes on HTR1B gene, able to amplify the HTR1B-rs13212041-T/T mediated effect of miR96. Overall, these data, obtained in two independent samples, shed new light on neurobiological correlates of psychopathy suggesting that HTR1B-rs13212041-T/T genotype might represent a biological correlate of psychopathy, useful to identify youths with deviant behavior particularly sensitive to parent maltreatment, who might benefit from early interventions aimed at improving their family environment to decrease their risk of developing psychopathy, with promising implications both at a clinical and forensic level.