Interactions Between Oxytocin Receptor Gene Methylation and Callous-Unemotional Traits Impact Socioaffective Brain Systems in Conduct-Disordered Offenders

Background: The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., perturbed socioaffective reactivity and empathy, callousness) in youths with conduct disorder (CD). Whereas oxytocin receptor gene methylation (OXTR_Meth) and its downstream neuromodulatory effects are deemed relevant to CU traits, nothing is known of how OXTR_Meth interacts with CU traits to impact socioaffective brain systems in youngsters with CD.

Methods: Hence, we uniquely probed OXTR_Meth × CU trait interactions on corticolimbic activity and amygdala subregional connections during recognition and resonance of distressing socioaffective stimuli (angry and fearful faces), in juvenile offenders with CD (n = 39) versus matched healthy control youths (n = 27).

Results: Relative to healthy control youths, elevated OXTR_Meth and CU levels in youths with CD essentially interacted to predict frontoparietal hyperactivity and amygdalo-frontoparietal disconnection during task performance. Specifically, increasing OXTR_Meth and CU levels in youths with CD interactively predicted midcingulate hyperactivity during both emotion conditions, with insular, temporoparietal, and precuneal hyperactivity additionally emerging during emotion recognition. Interactions between high OXTR_Meth and CU levels in youths with CD additionally predicted centromedial amygdala decoupling from ventromedial/orbitofrontal regions during emotion recognition, along with basolateral amygdala decoupling from precuneal and temporoparietal cortices during emotion resonance.

Conclusions: These results uniquely suggest that interactions between OXTR_Meth and CU traits in youths with CD may affect brain systems critical to decoding and integrating socioaffective information. Developmental models of CU traits and psychopathy could thus possibly advance by further examining OXTR epigenetic effects, which may hold promise for indicated prevention and personalized treatment by targeting oxytocinergic function.