Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder

Background: The lowering of mood induced by an acute tryptophan depletion ( ATD) has been proposed cis a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipola r affective disorder (BAD). Methods: In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devo id of tryptophan or a placebo, respectively. Clinical and biochemical effec ts of ATD were compared between unaffected relatives of BAD probands and ag e- and sex-matched control subjects. Results: At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84%, decreases in total plasma tryptophan concentration s in control subjects and relatives of patients with BAD, respectively. Unl ike control subjects unaffected relatives experienced a lowering of mood du ring ATD but not with the placebo. Furthermore, URs tended to show increase d impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity and fewer binding s ites of the serotonin transporter for imipramine; these differences it-ere unaffected by ATD. Conclusion: These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan avail ability. This finding mm, bear significance in the purported role of seroto nergic mechanisms in the vulnerability, to depressive syndrome and/or illne ss. (C) 2001 Society of Biological Psychiatry.