Serotonin (5-HT) has been implicated in the pathophysiology of bipolar disorders. Acute tryptophan depletion (ATD), which decreases serotonergic turnover, is an established paradigm to study serotonergic vulnerability in affective disorders. Literature on the application of ATD as a research tool in bipolar patients is limited to three studies, which revealed inconsistent results on mood modification. These inconsistencies may be attributed to differences in methodological procedures and / or characteristics of included patients. Patient selection, methodological aspects and procedures of these studies are critically considered and recommendations given. A research protocol to test the 5-HT vulnerability in bipolar disorder is proposed.

Serotonin (5-HT) is an important neurotransmitter involved in the brain–gut axis. It is possible to lower the 5-HT level in the body by means of a nutritional intervention using an amino acid mixture; the acute tryptophan depletion (ATD) method. We studied the effect of ATD on gastric emptying in healthy females, who received both ATD and placebo in a random order. Gastric emptying was measured using the [13C]octanoic acid breath test. The present data demonstrate significant differences in both gastric emptying and lag phase (Tlag) between the ATD and placebo experiment. Eight out of ten subjects showed a delayed gastric emptying in the ATD experiment. Both the gastric half-emptying time (T1/2) and the Tlag were significantly higher in the ATD experiment. T1/2 in the ATD experiment was 137·2 (range 76·2–634·8) min; T1/2 for the placebo experiment was 98·5 (range 63·7–168·8) min (P=0·028). Tlag in the ATD experiment was 83·7 (range 45·1–356·2) min; Tlag for the placebo experiment was 56·9 (range 23·2–101·2) min (P=0·007). We conclude that lowering the 5-HT level in the body using the ATD method leads to a significantly delayed gastric emptying of a solid meal. Nutritional manipulation of the serotonergic system in healthy volunteers may lead to alterations in gastrointestinal motility.