MAOA-VNTR polymorphism modulates context-dependent dopamine release and aggressive behavior in males.
A recent [(18)F]FDOPA-PET study reports negative correlations between dopamine synthesis rates and aggressive behavior. Since dopamine is among the substrates for monoamine oxidase A (MAOA), this investigation examines whether functional allelic variants of the MAOA tandem repeat (VNTR) promotor polymorphism, which is known to modulate aggressive behavior, influences dopamine release and aggression in response to violent visual stimuli. We selected from a genetic prescreening sample, strictly case-matched groups of 2×12 healthy male subjects with VNTRs predictive of high (MAOA-High) and low (MAOA-Low) MAOA expression. Subjects underwent pairs of PET sessions (dopamine D2/3 ligand [(18)F]DMFP) while viewing a movie of neutral content, versus violent content. Directly afterwards, aggressive behavior was assessed by the Point Subtraction Aggression Paradigm (PSAP). Finally, PET data of 23 participants and behavioral data of 22 participants were analyzed due to post hoc exclusion criteria. In the genetic prescreening sample MAOA-Low carriers had significantly increased scores on the Buss-Perry Aggression Questionnaire. In the PET-study-group, aggressive behavior under the emotional neutral condition was significantly higher in the MAOA-Low group. Interestingly, the two MAOA-groups showed inverse dopaminergic and behavioral reactions to the violent movie: The MAOA-High group showed higher dopamine release and increased aggression after the violent movie; MAOA-Low subjects showed decreases in aggressive behavior and no consistent dopamine release. These results indicate a possible impact of the MAOA-promotor polymorphism on the neurobiological modulation of aggressive behavior. However, the data do not support approaches stating that MAOA-Low fosters aggression by a simple pro-dopaminergic mechanism.
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: tschlueter@ukaachen.de.
Thorben
T
Schlüter
Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany.
Oliver
O
Winz
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany.
Karsten
K
Henkel
Institute of Human Genetics, RWTH Aachen University, 52074 Aachen, Germany.
Thomas
T
Eggermann
Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany.
Siamak
S
Mohammadkhani-Shali
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany.
Claudia
C
Dietrich
Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany; Jülich/Aachen Research Alliance (JARA), Jülich/Aachen, Germany.
Alexander
A
Heinzel
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany.
Michel
M
Decker
Department of Neuropsychiatry and Psychosomatic Medicine, Oslo University Hospital, Oslo, Norway; Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
Paul
P
Cumming
Institute of Human Genetics, RWTH Aachen University, 52074 Aachen, Germany.
Klaus
K
Zerres
Institute of Nuclear Chemistry, University of Mainz, Mainz, Germany.
Markus
M
Piel
Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany; Jülich/Aachen Research Alliance (JARA), Jülich/Aachen, Germany; Department of Nuclear Medicine, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Felix M
FM
Mottaghy
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany; Jülich/Aachen Research Alliance (JARA), Jülich/Aachen, Germany.
Ingo
I
Vernaleken
D000374:Aggression / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D055815:Young Adult
D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D004298:Dopamine
Aggression; DMFP; Dopamine; MAOA; PET