A decrease in central serotonergic activity following plasma tryptophan depletion has been shown to provoke a deterioration of mood. We studied the impact of sex and aggressive traits on mood changes following tryptophan depletion in healthy volunteers. Twelve healthy subjects (6 males, 6 females, 24–31 years), who were screened for psychiatric and non-psychiatric medical illness, were administered a tryptophan-depleting amino acid mixture (TD) and a placebo mixture on two different occasions in a double-blind crossover design. Psychometric measures included the preliminary determination of aggressive traits and depression and repeated assessments of mood and emotionality. The tryptophan-free amino acid mixture caused a marked depletion of plasma tryptophan with lowest levels occurring between 3 and 5 h after TD. Maximum changes in mood occurred about 10 h after TD, but only in high-aggressive women who scored significantly higher in arousal, anger and depressed mood, whereas low-aggressive women and men did not show any effect of TD. In addition, we could not confirm an increase in aggressive mood (anger) after TD in males with higher scores of trait aggression, presumably because the level of trait aggression was not high enough in this group. Due to the small sample size, our results that tryptophan depletion exerts a rapid mood-lowering effect on healthy women with pre-existing aggressive traits can only be seen as preliminary and have to be confirmed in further studies with larger samples.

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