Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability.

We investigated (1) the mood response of normal women, without a family history of major affective disorder, to acute tryptophan depletion, and (2) the temporal stability of the mood change, within subjects, when rechallenged at least 1 month later. To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested. The control treatment was a nutritionally balanced amino acid mixture containing tryptophan. A marked lowering of plasma tryptophan (80% to 90%) was achieved by both depletions. Compared to the balanced condition, the women exhibited a significant lowering of mood after the first tryptophan depletion on the elation-depression (p < .05), energetic-tired (p < .005), confident-unsure (p < .01), and clearheaded-confused (p < .01) scales of the bipolar profile of mood states. Whereas a lowering of mood was not found in a comparable sample of males studied earlier, these results were similar to those obtained in healthy males at genetic risk for major affective disorder (MAD). Inasmuch as a family history of MAD and female sex are predisposing factors to depression, these results suggest that a mood-lowering response to acute tryptophan depletion may occur preferentially in subjects with a susceptibility to lowered mood. However, the mood response to tryptophan depletion exhibited poor temporal stability in individual subjects.