Monoamine oxidase A (MAO-A) is a brain enzyme that serves several physiologic functions, including metabolism of monoamine neurotransmitters and induction of pro-apoptotic signaling pathways. Increased brain MAO-A level is present in clinical disorders characterized by low mood states, whereas decreased brain MAO-A level is associated with higher trait impulsivity and aggression in healthy volunteers. Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are common psychiatric conditions that exact a high healthcare and societal burden. BPD is associated with acute episodes of severe dysphoria, and ASPD presents high levels of impulsivity and aggression. The overall aim of the thesis was to investigate MAO-A brain level in BPD and ASPD. The first experiment used [11C] harmine positron emission tomography (PET) to assess MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in females with BPD. Our results showed that MAO-A VT was elevated in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) of severe BPD compared to control groups. Greater PFC and ACC MAO-A VT was additionally associated with more severe mood symptoms and suicidality in BPD. The second experiment applied [11C] harmine PET to examine MAO-A VT in impulsive, violent male offenders with ASPD. We found that orbitofrontal cortex and ventral striatum (VS) MAO-A VT were lower in ASPD compared to controls. Behavioral, self-report, and clinician-rated measures of impulsivity were also negatively correlated with VS MAO-A VT. The third experiment employed functional magnetic resonance imaging to measure VS resting state functional connectivity (FC) in ASPD. Our results demonstrated functional coupling between superior VS and bilateral dorsomedial prefrontal cortex that was correlated with VS MAO-A VT, and functional coupling between inferior VS and right hippocampus that was anti-correlated with VS MAO-A VT. The observed FC patterns were additionally associated with measures of impulsivity. Taken together, this body of research implicates abnormal brain MAO-A level in the pathophysiology of two related yet distinct personality disorders and their symptom clusters. Novel interventions targeting abnormal brain MAO-A level could emerge as potential new therapeutics for these disorders.Ph.D.2017-06-30 00:00:0
