MAOA-VNTR genotype modifies dopaminergic and behavioral response to aggressive environments and provocations: An [18F]DMFP study

Objectives A recent [18F]FDOPA study linked dopamine transmission to aggression but ignored the release during aggressive situations and genetic factors. The present [18F]DMFP-PET study quantifies the changes of striatal D2-receptor availability and observable aggression in respect to peaceful vs. aggression-associated environments and in respect to the MAOA VNTR genotype (risk factor for aggression).

Methods 88 male healthy subjects were characterized in respect to the MAO-A VNTR genotype. A first group (n=12) with 3.5/4 copies of a DNA sequence in the MAO-A promotor (high activity) was invited to the PET study. A second case-matched group, showed 3/5 copies (low activity). All subjects performed two [18F]DMFP-scans (250 MBq Bolus injection; 99 min., SRTM): one scan while watching a railroad track video (Glacier Express), another scan while watching a movie including aggressive content (Sin City) using video projection glasses. Directly after each scan, the aggression provocation paradigm (PSAP) was carried out.

Results MAOA-H subjects showed lower baseline aggression (PSAP). In PET, mean baseline BPnd values were 1.6±0.3 in vNC, 1.4±0.2 in NAcc, and 1.9±0.3 in vPut. Only in the MAOA-H group, aggressive movies changed significantly aggressive behavior as well as the BPnd (dopamine release) in the vPut (0.09±0.13) and on trend-level in the vNC. Also correlations between PSAP-aggression and BPnd-changes were only present in this genetic group (r: +0.60, p=0.05).

Conclusions The MAO-A-VNTR polymorphisms is not only associated with different risks for aggressive behavior (MAO-A-Low: higher risks towards aggressive behavior, also observable in the present PSAP), but apparently causes also strong differences in the modulation of dopamine transmission under near-real-life conditions.

Research Support IZKF Aachen TP5