The effect of acute tryptophan depletion and fenfluramine on quantitative EEG and mood in healthy male subjects

Background: Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion (A TD) as a manipulation strategy aimed at lowering brain serotonin synthesis. In an attempt to widen the scope of the measurement probes used in these i nvestigations, the central actions of ATD and a subsequent dose of fenflura mine were examined via utilization of quantitative electroencephalography ( EEG) and mood ratings. Methods: Electroenceplzalograms (EEG) and subjective mood ratings were asse ssed in 28 healthy men before and after double-blind ingestion of a tryptop han-depleting (T-) amino acid mixture, or a nutritionally balanced (B) amin o acid mixture containing tryptophan, and again after a single-blind oral d ose of D,L-fenfluramine hydrochloride (60 mg). Results: Compared to the B mixture, the T- mixture reduced total plasma try ptophan by more than 75% 5 hours after ingestion. Tryptophan depletion was associated with a modest lowering of mood and a slowing of EEG as indicated by increases in delta amplitude. Fenfluramine caused no change in mood but increased fast wave (beta) activity in anterior recordings when administer ed after the T-, but nor after the B mixture. Conclusions: Quantitative EEG measurements may be a promising method for st udying the central mechanisms underlying serotonin-mediated changes in mood and behavior: (C) 1999 Society of Biological Psychiatry.