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

Abstract

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 VT), 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): F2,33=6.8, P=0.003; OFC and VS MAO-A VT each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F7,28=2.7, P=0.029). In ASPD, VS MAO-A VT 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.

The role of monoamine oxidase A in aggression: Current translational developments and future challenges

“…These results underscore the importance of MAOA in antisocial behavior and point to this enzyme as a biomarker for aberrant aggression. In support of this idea, recent studies have documented lower MAOA distribution volume in patients affected by antisocial personality disorder (Kolla et al, 2015). …”

A Systematic Literature Review of Neuroimaging of Psychopathic Traits

“…Another candidate is the X-linked monoamine oxidase A (MAOA) gene and its high (MAOA-H) and low activity alleles (MAOA-L) (183). Individuals with absent or low acting MAOA are more prone to aggressive and impulsive behavior and exhibit higher psychopathic traits (184). Furthermore, identifying genes may reveal viable biomarkers for psychopathy.…”

Trait Anger, Physical Aggression, and Violent Offending in Antisocial and Borderline Personality Disorders

“…To address this issue and increase the robustness of the analyses, BPD and ASPD subjects were combined into a single group. Although ASPD and BPD have been conceptualized as different aspects of the same disorder manifested in a gender‐specific manner , it is now widely accepted that the two conditions are separate disorders , with growing research to suggest that ASPD and BPD have distinct neurobiological underpinnings . While externalized aggression is a DSM‐5 diagnostic criterion for both disorders and several laboratories investigating aggression include mixed samples of ASPD and BPD subjects , it is likely that there are subtle differences in the personality characteristics of ASPD and BPD underlying high trait physical aggression.…”