The Effects of Acute Tryptophan Depletion on Reactive Aggression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Healthy Controls

Abstract

BackgroundThe neurotransmitter serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD), a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD), and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD.Methodology/Principal FindingsTwenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA) beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT) and a TRP-balanced AA beverage (BAL) in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 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. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD.Conclusions/SignificanceTogether with previous findings, the data provide preliminary evidence of an inverse association between trait-impulsivity and the ATD effect on reactive aggression after LP (as assessed by the PSAG) in patients with ADHD and that this relationship can be found in both adolescents and adults. Because of limited statistical power larger sample sizes are needed to find main effects of ATD/BAL administration on reactive aggression in adults with ADHD.

The impact of acute tryptophan depletion on attentional performance in adult patients with ADHD

“…Our group recently demonstrated an interaction between ATD and reactive aggressive behavior in the present sample. Adult patients with ADHD showed increased reactive aggression in a Point Subtraction Aggression Game after ATD when compared with BAL (32). Further research detected that highly hostile aggressive patients showed increased inhibition errors after acute tryptophan depletion when compared with a control condition (54).…”

“…In patients with ADHD the number omissions increased after ATD administration when compared with BAL, and patient's reaction time decreased after ATD when compared with BAL intake, a finding that was contrasted by opposite effects in controls. Demographic data of the ADHD group and the control group studies examined the effects of ATD on memory performance (53), reactive aggression in adult patients (32), and reactive aggression in young people with ADHD (54). Previous studies assessing sustained attention in a Go/No-go paradigm only detected effects between groups, and an effect of ATD on omissions or RT has not been reported previously (51,53).…”

“…Few studies to date have investigated the impact of ATD in patients with ADHD. These studies examined the effects of ATD on memory performance (53), reactive aggression in adult patients (32), and reactive aggression in young people with ADHD (54). Sambeth et al (53) noted that delayed recall in a memory task was impaired after ATD.…”

“…The study sample is identical with the one in previous research (32). The study sample is identical with the one in previous research (32).…”

“…The patients were recruited from a pool of male adult patients with ADHD who were receiving treatment at the ADHD out-patient clinic of the Department of Psychiatry and Psychotherapy, University of Duisburg-Essen. The study sample is identical with the one in previous research (32). Patients with an IQ below 85 were not included in the study.…”