Intranasal oxytocin modulates brain activity during emotional processing in children with treatment resistant conduct problems

Abstract

One of the most highly replicated neural correlates of Conduct Problems (CP) is amygdala hypoactivity to another person's fear. We recently reported that this correlate was only observed in boys with persistent CP (i.e. antisocial behaviour that persisted following a gold-standard psychological intervention), suggesting that amygdala hypoactivity to fear could be an important neural signature for treatment-resistant CP, and a putative target for future treatments. Potential treatment candidates include the oxytocin system, as this has been reported to modulate amygdala activity and social behaviour across species. Further, in adults with antisocial personality disorder, intranasal oxytocin improved facial emotion recognition for fearful and happy faces. However, to-date, no-one has studied whether intranasal oxytocin can normalise neural processing differences in children with CP. Twenty boys (mean age 9.85±1.26 years) with persistent CP underwent functional magnetic resonance imaging in a within-subject randomised control design to investigate whether, compared to placebo, a single-dose of intranasal oxytocin could 'shift' abnormal neural processing to fear. Oxytocin failed to reduce amygdala hypoactivity to fearful faces, but increased activation in the posterior cingulate cortex / precuneus to happy faces. These findings tentatively suggest that intranasal oxytocin may promote a more neurotypical profile in treatment-resistant CP children, therefore, supporting the merit of investigating oxytocin in further larger clinical studies in this population.