Tryptophan depletion and depressive vulnerability

Background: Rapid and transient depletion of tryptophan (TRP) causes a brie f depressive relapse in most patients successfully treated with and taking selective serotonin reuptake inhibitors, but little change in drug-free, sy mptomatic depressed patients. This study investigates the effects of TRP de pletion in drug-free subjects in clinical remission from a prior major depr essive episode (MDE), Methods: Twelve subjects with a prior MDE, currently in clinical remission and drug-free for at least 3 months (patients), and 12 healthy subjects wit hout personal or family history of Axis I disorder (controls), received TRP depletion. The study was conducted in a double-blind controlled [full (102 -g) and quarter-strength (25 g) 15-amino acid drinks], crossover fashion. B ehavioral ratings and plasma TRP levels were obtained prior to, during, and after testing, Results: All subjects experienced significant depletion of plasma TRP on bo th test-drinks, showing a significant close-response relation, Healthy cont rol subjects had minimal mood changes, but patients had a depressive respon se of greater magnitude, Conclusions: In the context of prior TRP depletion studies with antidepress ant-treated and drug-free symptomatic depressed patients, these results sug gest that depression may be caused not by an abnormality of 5-HT function, but by dysfunction of other systems or brain regions modulated by 5-HT. Bio l Psychiatry 1999;46:498-505 (C) 1999 Society of Biological Psychiatry.