Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [11C] Harmine Positron Emission Tomography Study

Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [C-11] harmine PET to measure MAO-A total distribution volume (MAO-A V-T), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A VT were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F-2,F-33 = 6.8, P = 0.003; OFC and VS MAO-A V-T each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F-7,F-28 = 2.7, P = 0.029). In ASPD, VS MAO-A V-T was consistently negatively correlated with self-report and behavioral measures of impulsivity (r = -0.50 to -0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity.