title: The impact of dopamine on aggression: an [18F]-FDOPA PET Study in healthy males.
abstract: Cerebral dopamine (DA) transmission is thought to be an important modulator for the development and occurrence of aggressive behavior. However, the link between aggression and DA transmission in humans has not been investigated using molecular imaging and standardized behavioral tasks. We investigated aggression as a function of DA transmission in a group of (N = 21) healthy male volunteers undergoing 6-[18F]-fluoro-L-DOPA (FDOPA)-positron emission tomography (PET) and a modified version of the Point Subtraction Aggression Paradigm (PSAP). This task measures aggressive behavior during a monetary reward-related paradigm, where a putative adversary habitually tries to cheat. The participant can react in three ways (i.e., money substraction of the putative opponent [aggressive punishment], pressing a defense button, or continuing his money-making behavior). FDOPA-PET was analyzed using a steady-state model yielding estimates of the DA-synthesis capacity (K), the turnover of tracer DA formed in living brain (kloss), and the tracer distribution volume (Vd), which is an index of DA storage capacity. Significant negative correlations between PSAP aggressive responses and the DA-synthesis capacity were present in several regions, most prominently in the midbrain (r = -0.640; p = 0.002). Lower degrees of aggressive responses were associated with higher DA storage capacity in the striatum and midbrain. Additionally, there was a significant positive correlation between the investment into monetary incentive responses on the PSAP and DA-synthesis capacity, notably in the midbrain (r = +0.618, p = 0.003). The results suggest that individuals with low DA transmission capacity are more vulnerable to reactive/impulsive aggression in response to provocation.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, and Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany, ABX Chemicals, 01454 Radeberg, Germany, Department of Nuclear Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, 113-8654 Tokyo, Japan, Department of Anesthesiology, University Hospitals of the KU Leuven, 3000 Leuven, Belgium, Jülich/Aachen Research Alliance (JARA), 52074 Aachen, Germany, Department of Anesthesiology, University Hospital of the RWTH Aachen University, 52074 Aachen, Germany, and Department of Nuclear Medicine, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
authors.forename: Thorben
authors.initials: T
authors.lastname: Schlüter
authors.forename: Oliver
authors.initials: O
authors.lastname: Winz
authors.forename: Karsten
authors.initials: K
authors.lastname: Henkel
authors.forename: Susanne
authors.initials: S
authors.lastname: Prinz
authors.forename: Lena
authors.initials: L
authors.lastname: Rademacher
authors.forename: Jörn
authors.initials: J
authors.lastname: Schmaljohann
authors.forename: Kai
authors.initials: K
authors.lastname: Dautzenberg
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumakura
authors.forename: Steffen
authors.initials: S
authors.lastname: Rex
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
mesh_terms: D000328:Adult; D000374:Aggression; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000502:physiology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012201:Reward
chemical_list: D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine