Background: The present study investigated the effects of rapid tryptophan depletion (RTD), and the ensuing reduction of central nervous system levels of serotonin (5-HT), upon reactive aggression in patients with attention deficit/hyperactivity disorder (ADHD). Furthermore, it was asked whether the relation between 5-HT function and behavioural aggression in patients is influenced by their age, the intensity of their attention problems or their comorbid symptoms. Methods: The study employed a double-blind, within-subject crossover design. On day 1, 22 male adolescent patients with ADHD were subjected to RTD and the subsequent reduction of central 5-HT levels. On day 2, they received a tryptophan-balanced amino acid mixture (BAL), which acted as a placebo. On both days, 4.5 h after the intake of the RTD/BAL amino acids, reactive aggressive behaviour was provoked using a competitive reaction time game, which consisted of both high and low provocation conditions. Results: The number of aggressive responses was significantly higher after low provocation during acute tryptophan depletion, in comparison to the placebo. Furthermore, this study provides evidence that neither age nor the intensity of attention symptoms in ADHD patients had an impact on the relation between 5-HT and reactive aggression. Conclusion: This study indicates that in children with ADHD, there is an inverse relationship between 5-HT and aggression.
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