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 11 C 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 V T were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F 2,33 =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 7,28 =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.
CITATION STYLE
Kolla, N. J., Matthews, B., Wilson, A. A., Houle, S., Michael Bagby, R., Links, P., … Meyer, J. H. (2015). 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. Neuropsychopharmacology, 40(11), 2596–2603. https://doi.org/10.1038/npp.2015.106
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