Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Acute tryptophan depletion can induce a transient reappearance of depressive symptoms in recovered depressed patients. The neurochemical mechanism is thought to be impairment of brain serotonin neurotransmission, but the neuropsychologic mechanisms underlying the effect are unclear. METHODS: To assess whether low-dose tryptophan depletion can tease out the psychological mechanisms sensitive to substrate depletion in vulnerable subjects without inducing mood changes, a between-subjects randomized design was used. Recovered depressed patients (n = 24) and healthy volunteers (n = 24) were administered while fasting either a tryptophan-free or a control mixture, containing 31.2 and 33.2 g of amino acids, respectively. Objective and subjective ratings of mood were made before and 5 hours after ingestion; at the latter time point, cognitive and emotional processing were also assessed. RESULTS: Low-dose tryptophan depletion did not affect mood. Significant changes in emotional and cognitive processing occurred in the recovered depressed group, however, and to a lesser extent in the healthy volunteers. The profile of effects seen in the recovered patients suggested a return of the impairments seen in acute depression. CONCLUSIONS: Our data suggest that low-dose tryptophan depletion permits investigation of the cognitive correlates of acute reductions in brain serotonin in populations vulnerable to depression and in healthy volunteers, without causing depressive symptoms.

Original publication




Journal article


Biol Psychiatry

Publication Date





517 - 524


Adult, Amino Acids, Brain Chemistry, Case-Control Studies, Chromatography, High Pressure Liquid, Cognition, Depression, Diet, Protein-Restricted, Electromyography, Emotions, Facial Expression, Female, Humans, Male, Memory, Pain Measurement, Psychiatric Status Rating Scales, Psychological Tests, Reflex, Startle, Tryptophan, Verbal Learning