Background. Serotonergic mechanisms have been proposed for the pathophysiology of seasonal
affective disorder (SAD) and the therapeutic effect of bright-light treatment. Previously, we showed
that SAD patients, in clinical remission with light therapy during the winter, experienced transient
depressive relapses after a rapid tryptophan depletion (RTD) technique, which results in decreased
brain serotonin levels. The objective of this study was to investigate the effect of RTD in SAD
patients who were in natural summer remission.
Methods. Twelve drug-free patients with SAD by DSM-IV criteria and 10 normal subjects
participated in this double-blind, placebo-controlled, crossover study. SAD patients were in natural
summer remission for at least 8 weeks. Behavioural ratings and plasma tryptophan levels were
obtained before, and 5 h after, ingesting an amino acid (AA) mixture±tryptophan. Experimental
RTD and control sessions were scheduled 1 week apart.
Results. The RTD session resulted in significant reduction in total and free plasma tryptophan
levels compared to the control session. The behavioural data were analysed using repeated measures
analysis of variance. This analysis found significant main effects of time (higher scores after AA
ingestion) and diagnosis (higher scores in SAD patients), but no main effect of session or significant
interaction effects between the three factors. Thus, there were no significant behavioural effects of
RTD compared to the sham depletion control session.
Conclusions. The summer remission experienced by SAD patients is not dependent on plasma
tryptophan levels (and presumably brain serotonin function) in the same manner as that of
remission after light therapy. These results conflict with those of other laboratories, perhaps because
of differences in study samples.