Tryptophan and 5-HT in Psychiatric Illness

Abstract

Brain serotonin (5-HT) content is dependent on plasma levels of tryptophan (TRP). Rapid, transient depletion of TRP in humans can be accomplished by oral administration of a TRP-free amino acid mixture. This procedure leads to a 30 to 50% decrease in brain 5-HT levels in laboratory animals and decreases human plasma TRP levels by 70–80% in 5 hours. TRP depletion alters human behaviour in different ways depending on the gender and clinical status of the subject. This presentation will review current experience with TRP depletion in healthy subjects, depressed patients, panic disorder patients, obsessive compulsive disorder (OCD) patients, and medication-free, psychiatrically-well subjects with a prior history of major depression. TRP depletion causes a transient return of anxiety and depressive symptoms in antidepressant-treated psychiatric patients, regardless of diagnosis. In contrast, TRP depletion causes minimal change in symptoms in healthy subjects or in actively ill, medication-free patients with OCD, panic disorder or major depression. These results suggest that antidepressant drugs treat depressive and anxiety symptoms by enhancing 5-HT neurotransmission but dysfunction of the 5-HT system may not be the immediate cause of OCD, panic disorder, or major depression.