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.

The authors have declared no competing interest.

NCT05383300

Funding for the research study was provided by Wellcome Clinical Research Training Fellowship grant for JT (grant no. 200099/S/15/S). Additional funding and financial support of the research team (JG, DMa, DMu, NG) was provided by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC) and an Economic and Social Research Council (ESRC) grant to YP (grant no. ES/K009400/1). The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, ESRC, NIHR or the Department of Health and Social Care.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The London City and East Research Ethics Committee (15/LO/1083) and the National Offender Management Services Research Committee (2016-382) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes