Acute tryptophan depletion in healthy young women with a family history ofmajor affective disorder

Background. Acute tryptophan depletion (ATD), a means of reducing brain ser otonin synthesis, lowers mood in normal males with a multi-generational fam ily history of major affective disorder (MAD) and in normal women devoid of any family history of psychiatric illness. As both a family history of MAD and female sex are factors predisposing to depression, the hypothesis that a mood lowering response to ATD may reflect a susceptibility to depression was further investigated in young women with an extensive, multi-generatio nal family history of MAD. In addition, the temporal stability of mood chan ge following repeated trials of ATD was also assessed in this study. Methods. To deplete tryptophan, a tryptophan deficient amino acid mixture w as ingested on two separate occasions. The control treatment, administered on a third occasion, was a nutritionally balanced amino acid mixture contai ning tryptophan. Results. A marked lowering of plasma tryptophan (85-90%) was achieved by bo th depletions. In comparison to the balanced condition, family history posi tive (FH +) women showed no lowering of mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood change between the two ATD tri als (N = 13) exhibited poor temporal stability. Conclusions, These results may indicate that serotonin responsiveness is no t an important characteristic of vulnerability to depression in these women . Alternately, these negative results may be due to the exclusion of a larg e number of FR + women who had already experienced an episode of depression , resulting in the selection of a. biased FH+ sample who are resistant to t he mood lowering effects of ATD.