Brain structure, function and response to oxytocin in violent offenders with antisocial personality disorder and psychopathy

Student thesis: Doctoral ThesisDoctor of Philosophy


About 1% of the population is responsible for most violent crime. These individuals are typically male, have life course persistent antisocial behaviour, and meet diagnostic criteria for conduct disorder in childhood and for antisocial personality disorder (ASPD) in adulthood. Some of these individuals are additionally characterized by traits of callous unconcern in childhood and psychopathic traits in adulthood (ASPD+P). There is evidence that these individuals engage in offending behaviour from a younger age, employ more instrumental aggression, and are less responsive to punishment and treatment than individuals who have ASPD without psychopathy (ASPD-P). These two ASPD subtypes are associated with different neurocognitive and neurobiological mechanisms. It remains to be investigated whether ASPD+/-P groups also differ in terms of cortical structure or resting-state brain function. Furthermore, it has never been investigated whether potential functional brain abnormalities can be pharmacologically modulated, or ‘shifted’, to be more in line with typical brain function. One pharmacological agent of interest is oxytocin, a social neuropeptide. Studies in healthy individuals suggest that the intranasal administration of exogenous oxytocin can modulate processes that have been identified to be abnormal in ASPD and/or psychopathy.

The current study had two aims. First, to further investigate neurobiological underpinnings of ASPD+P and ASPD-P relative to non-offending healthy controls in terms of brain structure (cortical volume, surface area, cortical thickness) and resting-state brain function (regional cerebral blood flow, large-scale network functional connectivity, and network topology).
Second, to assess the effect of intranasal oxytocin on resting-state brain function.

The study used a double-blind, placebo-controlled, randomized crossover design. Adult males with past violent convictions who met Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria for ASPD were recruited from South London forensic and probation services. They were3
stratified into ASPD+P and ASPD-P groups according to the European threshold for psychopathy on the Psychopathy Checklist-Revised. Healthy adult non-offending males were recruited from the South London community. After self-administering the placebo and oxytocin nose sprays, all participants underwent structural magnetic resonance imaging (MRI), arterial spin labelling imaging, and resting-state functional MRI (fMRI) scans.

Individuals with ASPD+P and ASPD-P showed significant brain structure abnormalities relative to non-offenders in frontotemporal and medial parietal cortical volume, surface area, and cortical thickness, with significant differences between the ASPD subtypes. The arterial spin labelling study revealed significant reductions in frontotemporal cerebral blood flow in both antisocial groups relative to non-offenders, and significant increases in medial parietal cerebral blood flow in both antisocial groups relative to non-offenders, that was also significantly higher in ASPD+P than ASPD-P. Functional connectivity analyses of resting-state fMRI data revealed that individuals with ASPD showed significant abnormalities within several large-scale networks, including medial-temporal and salience networks relative to non-offenders. Topological analyses of resting-state fMRI data demonstrated significant differences in brain network topology in ASPD at macro-, meso-, and micro-levels in comparison to non-offenders. Intranasal oxytocin significantly attenuated resting-state brain abnormalities in the ASPD group in all three functional investigations.

These findings provided further support for differences in the neurobiological mechanisms between violent offenders with ASPD+P and ASPD-P. Moreover, they provided the first evidence that intranasal oxytocin can modulate resting-state brain function in these individuals. The results have important implications for stratification within the ASPD diagnostic group, as well as for the therapeutic potential of intranasal oxytocin.
Date of Award1 Jun 2023
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorNigel Blackwood (Supervisor) & Declan Murphy (Supervisor)

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