Can formulation affect tryptophan depletion results? Hints from studies in experimental panic

Rationale: Acute Tryptophan Depletion (ATD) is a specific serotonergic challenge tool. Central serotonergic effects of different ATD procedures are possibly not those that are usually assumed. Objectives: In this paper we review data of ATD in an experimental fear model to investigate whether and how methodological differences may affect fear outcomes. Next we point to discrepancies of studies in our laboratory in order to test the hypotheses formulated in the review. Methods: Literature was searched in PubMed and MEDLINE and studies of our laboratory were compared. Results: Eight studies were included in the review: five in patients with panic disorder, three in healthy individuals. Methodologically the studies in our laboratory were quite similar except for the applied ATD mixtures. Conclusions: ATD exerts fear-enhancing effects in patients with panic disorders, more than in healthy individuals. However, our findings are inconclusive. The discrepant findings of studies in our laboratory can possibly be explained by differences in the ATD mixtures used. We suggest mechanisms as to how these might have affected the central availability of tryptophan and hence serotonin.