Serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior in studies in animals as well as humans. Even with some research trying to shed light on this question, the exact neurobiology of aggression remains unclear in the context of ADHD, a disorder commonly associated with aggression and impulsivity. Acute tryptophan depletion (ATD) allows for an investigation of the effects of diminished central nervous serotonergic neurotransmission on reactive aggression.

A study by Zimmermann et al (2012, PLoS One) approached the issue of the relationship between aggression and serotonin by investigating reactive aggression of male patients with ADHD and healthy male controls. The setup of the study was close to a study conducted by Zepf et al in which both groups were subjected to ATD or a balanced control mixture (BAL) in a double-blind, within-subject crossover-study over two study days. Reactive aggression was assessed 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG) in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP), with controls showing the opposite effect. It was also shown that in patients with ADHD trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. In summary with findings of other studies, these results provide preliminary evidence of an inverse association between trait-impulsivity and the ATD effect on reactive aggression after LP in patients with ADHD and that this relationship can be found in both adolescents and adults.

These results contrast other findings, e.g. Stadler et al (2007, Neuropsychobiology) and Zepf et al (2008, Human Psychopharmacology), who showed, that there is an inverse relationship between serotonin and aggression when investigating the effects of ATD in children with ADHD.