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]
^Ruhé HG, Mason NS, Schene AH (April 2007). "Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies". Molecular Psychiatry. 12 (4): 331–59. doi:10.1038/sj.mp.4001949.
