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.

Figure 1.

A, Relationship between the aggressive response ratio (Aggressive Ratio) and FDOPA-V_d (ml g⁻¹; index of dopamine storage capacity) in NC, thalamus, and midbrain; correlation in thalamus reached significance (r = −0.497, p = 0.022; n = 21; two-tailed rank-order correlation). B, Relationship between Aggressive Ratio and FDOPA-K (ml g⁻¹ min⁻¹; index of dopamine synthesis capacity). Significant correlations in the NC (r = −0.444, p = 0.044; n = 21; two-tailed rank-order correlation) and midbrain (r = −0.640, p = 0.0002; n = 21; two-tailed rank-order correlation). For illustration, the solid line represents the linear regression line.