Effect of MAOA-VNTR Polymorphism on Aggression and Dopamine Releasse

Objectives One of the most stable genetic findings on human aggressive behavior refers to the MAOA VNTR (variable number of tandem repeats) polymorphism. The neurobiological pathways behind this association remain, however, unknown. Besides serotonergic modulations, also the MAOA substrate dopamine regulates aggressive reactions. Furthermore it is well known that aggression also depends on provocation and the exposure to proaggressive circumstances. The present investigation combines these influencing factors in one protocol.

Methods From a genetic sample, 2x12 case-matched healthy male subjects with MAOA-VNTR genotype predictive of high (MAOA-High) and low (MAOA-Low) MAOA expression were included. For measuring situational dopamine release, subjects underwent two [18F]DMFP-PET scans while viewing a neutral content movie, versus a movie with aggressive violent content. Directly afterwards, provocable aggressive behavior was assessed by the well validated Point Subtraction Aggression Paradigm (PSAP). PET data were analyzed using the SRTM in a VOI-based and a parametric voxel-based approach.

Results MAOA-Low carriers had significantly higher aggression scores on the BPAQ. Aggressive behavior under the neutral condition was significantly higher in the MAOA-Low group. Genotype was a significant predictor for ΔBPND (F=5.074, p=0.005, df=5/17) in a MANOVA. The two MAOA-groups showed inverse dopaminergic and behavioral reactions in respect 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. In this group, the change in aggression tended to correlate negatively with the change in ventral striatal binding potentials.

Conclusions These results indicate strong 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. Feedback mechanisms might be relevant confounders.

Research Support IZKF Aachen.