Acute tryptophan depletion – a translational research method for studying the impact of central nervous system serotonin function

Serotonin (5-HT) is a neurotransmitter that is thought to play a decisive role in many psychiatric disorders. The present special issue of the journal is composed of a selection of articles using the acute tryptophan depletion (ATD) technique, which is a safe physiological neurodietary method for lowering the synthesis rate of the neurotransmitter 5-HT in the brain. On one hand, studying the effects of a specific neurotransmitter on individuals may be realized by enhancing central nervous system neurotransmission of said neurotransmitter; in the case of 5-HT, administration of selective serotonin reuptake inhibitors (SSRIs) is one method for accomplishing this task. On the other hand, one may also try to draw conclusions about such effects by decreasing the availability of the neurotransmitter and comparing the resulting data with those gathered at a baseline assessment or from a control condition, an approach somewhat reversed from the first method. The aforementioned ATD method relies upon decreased administration of the essential amino acid tryptophan (TRP), the physiological precursor of 5-HT, to achieve a short-term reduction in brain 5-HT synthesis (1, 2). By assessing changes in behavior (3, 4), physiological parameters (5), brain function (6), and neurochemical properties (2) following ATD administration and comparing the resulting findings to baseline or control conditions, researchers can draw conclusions about the effects of 5-HT on the brain and behavioral characteristics as well as biological variables. In other words, ATD exemplifies the concept of trying to draw conclusions about brain 5-HT function with respect to the effects observed, while subjects are under the influence of a short-term deficit in central nervous system 5-HT synthesis. In this issue of Acta Psychiatrica Scandinavica, K€ otting et al. (7) present data on the effects of a body weight–adapted ATD protocol in young people with attention deficit hyperactivity disorder (ADHD) with respect to aggressive behavior. This is the first published study investigating the effects of ATD on aggressive behavior that included female youths with ADHD. The results describe the differential effects of ATD on aggression in female and male youths with ADHD depending upon levels of provocation. Mette et al. (8) describe significant differences in attentional performance (omission errors) found in adult patients with ADHD and controls while subjected to ATD when compared with a control condition. Moreover, the patients’ reaction times decreased following ATD when compared with the control condition, whereas the opposite effects were observed in the control group. These observations implicate serotonergic neurotransmission in attentional processes in adults with ADHD – a finding of importance with respect to the still not fully understood pathophysiology of ADHD. Grabemann et al. (9) studied the effects of ATD on affective prosody in adult patients with ADHD, but did not find clear evidence supporting an association of 5-HT with impairments in affective prosody in these patients. Instead, difficulties in accurately processing affective prosody in male adults with ADHD may be associated with significant impairments in their ability to inhibit unwanted stimuli and impulses. Another study (10) examined the effects of ATD on verbal declarative memory in young people with ADHD; no clear effects were identified. Despite such non-significant findings, such information is of scientific value, especially considering that the pathophysiology of ADHD is not entirely understood. Also in this special issue of the journal, van Donkelaar et al. (11) show that changes in central nervous system 5-HT function might not play as important a role as previously thought in acting as a mechanism behind the previously reported ability of phosphodiesterase inhibitors to improve Video podcast available Go to www.actapsychiatrica. com to watch an accompanying commentary by Guest Editor Florian Daniel Zepf.