Background. Acute tryptophan depletion (ATD), a means
of reducing brain serotonin synthesis,
lowers mood in normal males with a multi-generational family 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-generational family history of MAD.
In addition, the
temporal stability of mood change following repeated trials of ATD was
also assessed in this study.
Methods. To deplete tryptophan, a tryptophan deficient amino
acid mixture was ingested on two
separate occasions. The control treatment, administered on a third occasion,
was a nutritionally
balanced amino acid mixture containing tryptophan.
Results. A marked lowering of plasma tryptophan (85–90%)
was achieved by both depletions. In
comparison to the balanced condition, family history positive (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 trials (N=13) exhibited poor temporal stability.
Conclusions. These results may indicate that serotonin responsiveness
is not an important
characteristic of vulnerability to depression in these women. Alternately,
these negative results may
be due to the exclusion of a large number of FH+ women who had already
experienced an episode
of depression, resulting in the selection of a biased FH+ sample who are
resistant to the mood
lowering effects of ATD.