Acute tryptophan depletion explained

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.^[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. 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]

Notes and References

1. van Donkelaar EL, Blokland A, Ferrington L, Kelly PA, Steinbusch HW, Prickaerts J . Mechanism of acute tryptophan depletion: is it only serotonin? . Molecular Psychiatry . 16 . 7 . 695–713 . July 2011 . 21339754 . 10.1038/mp.2011.9 . free .
2. Young SN . Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects . Journal of Psychiatry & Neuroscience . 38 . 5 . 294–305 . September 2013 . 23428157 . 3756112 . 10.1503/jpn.120209 .
3. Ruhé HG, Mason NS, Schene AH . 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 . April 2007 . 10.1038/sj.mp.4001949.
4. Jauhar S, Arnone D, Baldwin DS, Bloomfield M, Browning M, Cleare AJ, Corlett P, Deakin JF, Erritzoe D, Fu C, Fusar-Poli P, Goodwin GM, Hayes J, Howard R, Howes OD, Juruena MF, Lam RW, Lawrie SM, McAllister-Williams H, Cowen PJ . (2023). A leaky umbrella has little value: Evidence clearly indicates the serotonin system is implicated in depression. . Molecular Psychiatry . 28 . 8 . 3149–52 . 10.1038/s41380-023-02095-y. 10618084 .