Background. Deficiencies in brain serotonin function are
believed to play an important role in the
pathophysiology of seasonal affective disorder/winter type (SAD).
However, no direct evidence has
been reported so far that lowered brain serotonin activity causes the symptoms
Methods. We studied 11 SAD patients who had suffered
recurrent winter depressive episodes of
SAD and were fully recovered and off treatment during the summer. In a
double-blind crossover design patients received two amino acid beverages,
tryptophan and the other containing no tryptophan but otherwise identical.
and plasma total and free tryptophan concentrations were assessed
at baseline before administration
of the amino acid beverages and at several time points afterwards.
Results. The tryptophan-free amino acid beverage induced
significant decreases of plasma total and
free tryptophan levels and both levels increased during sham depletion
P<0·001). Tryptophan depletion, but not sham depletion
caused a transient return of depressive
symptoms (condition×time interaction: P<0·001).
Conclusions. The present study demonstrates that SAD patients
in remission during the summer are
vulnerable to a return of depression when depleted of tryptophan. This
finding supports the
importance of serotonergic mechanisms in the pathophysiology of SAD.