Tryptophan and serotonin — MRCPsych Paper A MCQ

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EasyNeurophysiology and neurochemistryTryptophan and serotoninMRCPsych Paper A

A researcher uses acute dietary tryptophan depletion to investigate monoaminergic contributions to mood. The synthesis of which neurotransmitter is most directly reduced by this manipulation?

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Correct answer: A — Serotonin

The correct answer is **B, serotonin**. Tryptophan is the amino-acid precursor of serotonin (5-hydroxytryptamine). In serotonergic neurones, tryptophan hydroxylase converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin. Acute tryptophan depletion reduces tryptophan availability to the brain and therefore reduces serotonin synthesis; this is why it is used as an experimental serotonergic challenge. It should not be interpreted as proving that low serotonin alone causes depression. Dopamine is synthesised from tyrosine, histamine from histidine, and GABA from glutamate. Acetylcholine is formed from choline and acetyl-CoA. Thus, none of the alternative neurotransmitter pathways is directly dependent on tryptophan availability.

Reference: van Donkelaar E, Blokland A, Ferrington L, et al. Mechanism of acute tryptophan depletion: is it only serotonin? Molecular Psychiatry. 2011;16(7):695–713. https://pubmed.ncbi.nlm.nih.gov/21339754/