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

Abstract

Background: Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion (ATD) as a manipulation strategy aimed at lowering brain serotonin synthesis. In an attempt to widen the scope of the measurement probes used in these investigations, the central actions of ATD and a subsequent dose of fenfluramine were examined via utilization of quantitative electroencephalography (EEG) and mood ratings. Methods: Electroencephalograms (EEG) and subjective mood ratings were assessed in 28 healthy men before and after double-blind ingestion of a tryptophan-depleting (T−) amino acid mixture, or a nutritionally balanced (B) amino acid mixture containing tryptophan, and again after a single-blind oral dose of d,l-fenfluramine hydrochloride (60 mg). Results: Compared to the B mixture, the T− mixture reduced total plasma tryptophan 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 administered after the T−, but not after the B mixture. Conclusions: Quantitative EEG measurements may be a promising method for studying the central mechanisms underlying serotonin-mediated changes in mood and behavior.