AbstractA small group of men are responsible for most violent crimes, resulting in considerable interpersonal and societal costs. They meet diagnostic criteria for Conduct Disorder (CD) in childhood and Antisocial Personality Disorder (ASPD) in adulthood. Approximately one-third meet criteria for an additional diagnosis of psychopathy (ASPD+P), exhibiting callous unemotional (CU) traits from early in life, engaging in a broader range of offending behaviours, and responding less well to treatments than those without psychopathy (ASPD-P). Those with ASPD+P show particular deficits in empathic processing, while both ASPD+P and ASPD-P share deficits in decision-making. Evidence demonstrates that these clinical and neurocognitive differences may be explained by some shared, but some differential neurobiological underpinnings. However, the neurochemical underpinnings remain relatively under-researched. One neurochemical of particular interest is oxytocin- a neuropeptide shown to modulate empathic processing and decision-making in healthy populations. However, no study to date has examined its effect on neural processing of these functions in ASPD+/-P. The neurochemical underpinnings of shared decision-making deficits in ASPD+/-P also remain under-researched. One important consideration is regulation of striatal input into decision-making by Glutamate and GABA, which has not yet been examined in ASPD+/-P.
In this thesis, I sought to address these gaps in the literature. Firstly, using a double-blinded, placebo controlled design, I explored similarities and differences in i) an important component of empathic processing (neural response to facial emotional expressions) and ii) decision-making in violent men with ASPD+/-P (n= 26 across studies), compared to healthy non-offenders (NO; n= 21 across studies), with placebo and after acute application of intranasal oxytocin, using functional Magnetic Resonance Imaging (fMRI). Secondly, I investigated differences in striatal excitatory/inhibitory (E/I) balance between groups, as measured by Glutamate:GABA ratio, using Magnetic Resonance Spectroscopy (MRS). Subjects were classified using Psychopathy Checklist PCL-R scores. In the first fMRI study, in the placebo condition, the ASPD+P group showed reduced responsivity to fearful faces in in bilateral cingulate cortex, compared to ASPD-P. Further, oxytocin abolished these differences and enhanced activity in ASPD+P, in these regions and also in bilateral insula. In the second fMRI study, there were no significant behavioural findings. While the task elicited an overall effect across the sample in bilateral cerebellum (offer phase) and anterior cingulate cortex (decision phase), there were no effects of group or oxytocin. In the MRS study, both ASPD+P and ASPD-P had lower Glutamate:GABA ratios than NO, though there was no significant difference between ASPD+P and ASPD-P. Glutamate:GABA ratio correlated significantly with a reward-based decision metric from a neuropsychological task (‘Now or Later’ task).
Taken together, my findings provide further support for a model of some shared, but some differential neurocognitive deficits in ASPD+P and ASPD-P. They build on previous research supporting stratification of ASPD into subcategories of ASPD+P and ASPD-P. Importantly, for the first time, I have also demonstrated normalising effects of oxytocin in empathic processing in ASPD+P. This finding is a particularly important step forward towards developing targeted and effective interventions for this especially challenging patient population.
|Date of Award
|1 Apr 2021
|Nigel Blackwood (Supervisor) & Declan Murphy (Supervisor)