THE OXYTOCIN RECEPTOR RS-53576 A ALLELE MODULATES THE INFLUENCE OF ENVIRONMENTAL FACTORS ON SOCIAL BEHAVIOR

Background: Oxytocin (OXT) plays a key role in emotional and cognitive processes underlying social behavior. According to the “social salience” hypothesis, OXT increases the focus on relevant social aspects, promoting prosociality in response to positive social cues, or antisocial behaviors following negative social signals. Methods: We questioned whether rs53576 (a G>A change in the OXT receptor gene, OXTR), previously associated with psychopathy in adults and callous-unemotional (CU) traits in youths, may modulate vulnerability to both negative and positive experiences leading to either antisocial or altruistic behavior. To this aim, we investigated the influence of rs53576 on 1) psychopathic traits in response to negative experiences and 2) altruistic behavior in response to traumatic experiences with or without social support. Aim 1) Psychopathic traits were assessed by the CU subscale of the Antisocial Process Screening Device (APSD) in 106 Italian White male children (age: 7-12 years) with Conduct Disorders; by the Psychopathy Checklist: Youth Version (PCL:YV) in 136 US White male institutionalized adolescents (age: 14-18 years); and by the Psychopathy Checklist-Revised (PCL-R) in 397 US White male adult inmates (age: 19-65 years). Aversive experiences were assessed by the Negative Parenting subscale of the Alabama Parenting Questionnaire (APQ) in children, by a trauma checklist extracted from anamnestic data (TCL) in adolescents, and by both the Measure of Parental Style (MOPS) (n= 204) and the Barratt Simplified Measure of Social Status (BSMSS) (n= 397) in adults. Each participant provided a sample of saliva for genotyping. Aim 2) Altruism was measured by the Altruism Personality Scale (APS) in 308 (180 males) subjects (Volunteers) engaged in volunteering by nonprofit Italian organizations. Data concerning traumas and the consequent received support were collected by the Trauma Experience Checklist (TEC). Each participant provided a sample of saliva for genotyping. Results: The A allele modulated the correlations between a) CU traits and negative parenting (rs=0.376, p=0.006, n=53) in children with Conduct Disorder; b) antisocial behavior and trauma history (rs=0.319, p=0.003, n= 84) in institutionalized adolescents; c) antisocial behavior and both negative parenting (rs=0.226, p=0.015, n=116) and low social status (rs=-0.205, p=0.009, n=162) in institutionalized adults, explaining 11.8%, 3.7%, 5%, and 6.2% of the variance. The A allele also modulated the correlation between altruism and support received after traumas (rs=0.209, p=0.01, n=152) in Volunteers, explaining 5.5% of the variance. Discussion: Since rs53576 is thought to modulate OXTR gene methylation, we hypothesize that the A allele may potentiate the environmental effects by regulating OXTR expression. Our data shed new light on the nature vs. nurture debate in social behavior, by highlighting the relevant role of the environment, in combination with specific genetic variants, in shaping our way of behaving. As the environment, differently from genetics, can be modified by social and psychotherapeutic interventions, our findings hold important implications for preventing or correcting deviant behaviors and for promoting prosocial conduct in individuals who may possess a greater genetic vulnerability to environmental stimuli.