title: Association of ventral striatum monoamine oxidase-A binding and functional connectivity in antisocial personality disorder with high impulsivity: A positron emission tomography and functional magnetic resonance imaging study.
abstract: Impulsivity is a core feature of antisocial personality disorder (ASPD) associated with abnormal brain function and neurochemical alterations. The ventral striatum (VS) is a key region of the neural circuitry mediating impulsive behavior, and low monoamine oxidase-A (MAO-A) level in the VS has shown a specific relationship to the impulsivity of ASPD. Because it is currently unknown whether phenotypic MAO-A markers can influence brain function in ASPD, we investigated VS MAO-A level and the functional connectivity (FC) of two seed regions, superior and inferior VS (VSs, VSi). Nineteen impulsive ASPD males underwent [(11)C] harmine positron emission tomography scanning to measure VS MAO-A VT, an index of MAO-A density, and resting-state functional magnetic resonance imaging that assessed the FC of bilateral seed regions in the VSi and VSs. Subjects also completed self-report impulsivity measures. Results revealed functional coupling of the VSs with bilateral dorsomedial prefrontal cortex (DMPFC) that was correlated with VS MAO-A VT (r=0.47, p=0.04), and functional coupling of the VSi with right hippocampus that was anti-correlated with VS MAO-A VT (r=-0.55, p=0.01). Additionally, VSs-DMPFC FC was negatively correlated with NEO Personality Inventory-Revised impulsivity (r=-0.49, p=0.03), as was VSi-hippocampus FC with Barratt Impulsiveness Scale-11 motor impulsiveness (r=-0.50, p=0.03). These preliminary results highlight an association of VS MAO-A level with the FC of striatal regions linked to impulsive behavior in ASPD and suggest that phenotype-based brain markers of ASPD have relevance to understanding brain function.
authors.affiliation: CAMH Research Imaging Centre, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada; Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada. Electronic address: nathan.kolla@mail.utoronto.ca.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Kolla
authors.affiliation: Institute of Medical Science, University of Toronto, Canada; University Health Network, Canada.
authors.forename: Katharine
authors.initials: K
authors.lastname: Dunlop
authors.affiliation: Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada; University Health Network, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Downar
authors.affiliation: Institute of Medical Science, University of Toronto, Canada; Department of Psychiatry, University of Western Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Links
authors.affiliation: CAMH Research Imaging Centre, Canada; Department of Psychiatry, University of Toronto, Canada; Department of Psychology, University of Toronto, Canada.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Bagby
authors.affiliation: CAMH Research Imaging Centre, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada; Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: CAMH Research Imaging Centre, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada; Department of Psychiatry, University of Toronto, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: CAMH Research Imaging Centre, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada.
authors.forename: Fawn
authors.initials: F
authors.lastname: Rasquinha
authors.affiliation: Department of Psychiatry, University of Toronto, Canada.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Simpson
authors.affiliation: CAMH Research Imaging Centre, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada; Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000987:Antisocial Personality Disorder / Q000378:metabolism* / Q000503:physiopathology* / Q000523:psychology; D002250:Carbon Radioisotopes / Q000494:pharmacology; D059907:Functional Neuroimaging; D006247:Harmine / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D009434:Neural Pathways / Q000503:physiopathology; D010555:Personality Inventory; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000503:physiopathology; D011869:Radioligand Assay; D066328:Ventral Striatum / Q000378:metabolism* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D006247:Harmine; D008995:Monoamine Oxidase
keywords: Antisocial personality disorder; Functional magnetic resonance imaging; Impulsivity; Monoamine oxidase-A; Positron emission tomography; Violence