Converging evidence for central 5-HT effects in acute tryptophan depletion

Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned the validity of ATD.2 Although we agree that ATD's effects on 5-HT activity at the molecular level need further clarification, van Donkelaar et al.2 goes too far in challenging whether ATD exerts its effects through serotonergic mechanisms. There is strong evidence that ATD reduces brain 5-HT and disrupts stimulated 5-HT release,3, 4 and converging translational findings support a central role for brain 5-HT in ATD's effects on cognition and behavior