Rapid tryptophan depletion affects behavioural inhibition and cognitive flexibility in hostile children with ADHD

Background: Serotonergic (5-HT) functioning has been shown to account for a variety of behavioral characteristics, in particular aggressive and impulsive behavior. However, little is known about 5-HT mechanisms in children, and the effects of 5-HT on cognitive flexibility and behavioral inhibition, particularly in ADHD. In this investigation, we explored the effects of rapid tryptophan depletion (RTD) and the ensuing reduction of brain 5-HT synthesis on cognitive flexibility and inhibition in passive avoidance learning in a computerized go/no-go task. Methods: 22 male patients with a diagnosis of ADHD were administered RTD within an amino acid drink thus lowering the central nervous 5-HT synthesis rate in a placebo-controlled double-blind within-subject crossover-design. 4 hours after drink intake the patients were subjected to a Go/No-go task for assessment of behavioral inhibition and cognitive flexibility. Results: High hostile aggressive patients showed lower rates of cognitive flexibility related to increased inhibition errors and thus worsened cognitive flexibility under RTD compared to placebo. Low hostile aggressive patients showed lower rates of inhibition errors and thus better cognitive flexibility under RTD compared to placebo. Discussion: The data suggest that in ADHD levels of trait-aggressive characteristics influence the susceptibility to reduced rates of cognitive flexibility after an acute 5-HT dysfunction.