Resting-state brain function and its modulation by intranasal oxytocin in antisocial personality disorder with and without psychopathy

Behavioural, structural and functional neuroimaging differences have been demonstrated between individuals with antisocial personality disorder with (ASPD+P) or without psychopathy (ASPD-P). However, the underlying mechanisms for such differences are poorly understood, hampering progress in the development of drug treatments for this population. Intranasal oxytocin (OT) has garnered significant attention due to its prosocial effects in healthy individuals. We sought to establish the impact of OT on resting-state brain function in individuals with ASPD, and to explore whether modulation differs between individuals with and without psychopathy. We used arterial spin labelling (ASL) to measure regional cerebral blood flow (rCBF) to investigate brain function at rest and modulation of key disease-targets by a single acute dose of OT (40 IU). We used a double-blind, placebo-controlled, crossover design in males with a history of violent offending with ASPD+P (N = 17) or ASPD-P (N = 14) and a group of healthy male non-offenders (N = 22). Both ASPD subtypes showed reduced rCBF in frontotemporal regions compared to non-offenders. However, those with ASPD+P demonstrated significantly greater rCBF increases in posterior default mode network regions compared to those with ASPD-P. OT administration selectively reduced rCBF in the left basal ganglia of the ASPD-P group, an effect not observed in the ASPD+P or non-offender groups. Our results provide further evidence of functional brain differences between ASPD+P and ASPD-P groups, and a differential modulating effect of oxytocin. The neurobiological distinctions between ASPD+P and ASPD-P groups are important considerations for future therapeutic developments.