Mood effects of 24-hour tryptophan depletion in healthy first-degree relatives of patients with affective disorders

Background: Acute tryptophan (TRP) depletion was evaluated in healthy volunteers with or without a family history of major affective disorder (FH+ versus FH-). Methods: Twenty-seven subjects (16 FH+, 11 FH-) received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind cross-over design and a diet devoid of TRP for the next 24 hours. Results: The ratio TRP/large neutral amino acids declined to 22% of baseline values after 6 hours, and increased during the night reaching 85% of baseline after 24 hours. Overall, after 6 hours, TRP depletion lead to a lowering of mood, but after 24 hours, these changes were no longer detected. Mood changes and gastrointestinal side effects were significantly more evident in FH+ subjects than in FH- subjects. Conclusions: Our data support the hypothesis that subjects with a positive family history for depression are predisposed to increased vulnerability to the adverse consequences of serotonergic imbalance. Biol Psychiatry 1999;46:489-497 (C) 1999 Society of Biological Psychiatry.