title: Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [(11)C] 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.
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Kolla
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.
authors.forename: Brittany
authors.initials: B
authors.lastname: Matthews
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Bagby
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, University of Western Ontario, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Links
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Simpson
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.
authors.forename: Amina
authors.initials: A
authors.lastname: Hussain
authors.affiliation: Centre for Addiction and Mental Health (CAMH) Research Imaging Centre, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000704:Analysis of Variance; D000987:Antisocial Personality Disorder / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D057237:Criminals; D005715:Gambling; D006247:Harmine; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011581:Psychological Tests; D019275:Radiopharmaceuticals; D014754:Violence
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D006247:Harmine; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human