Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals

Rationale: Reduced serotonergic activity has been associated with impulsive behavior; however, intervention studies have been scarce. Objectives: To examine whether induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity. Methods: Twenty-four healthy young males ingested a mixture of the essential amino acids except for tryptophan in a balanced, randomized, double-blind, placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture. Results: The intervention led to a dramatic fall in free and total plasma tryptophan, and the tryptophan/large neutral amino acids ratio. This in turn has been shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive- or disinhibited response style on the continuous -performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli. Conclusions: These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients.