Acute tryptophan depletion

Acute tryptophan depletion (ATD) is a technique used extensively to study the effect of low serotonin in the brain.^[1] This experimental approach reduces the availability of tryptophan, an amino acid which serves as the precursor to serotonin.^[1][2] The lack of mood-lowering effects after ATD in healthy subjects seems to contradict a direct causal relationship between acutely decreased serotonin levels and depression. However, mood-lowering effects are observed in certain vulnerable individuals.^[1] For example, a meta-analysis show that the effect size for the effects of tryptophan depletion on mood in depressed people not taking antidepressants was large (Hedge's g = −1.9 (95% CIs −3.02 to −0.78) ^[3] Hence, a more accurate interpretation is that tryptophan depletion studies suggest a role for 5-HT in people vulnerable to depression and in those remitted on SSRI treatment ^[4]