Tryptophan depletion is a widely used model to study mechanisms related to the serotonin system in the pathophysiology and treatment of depression. There is compelling evidence that tryptophan depletion primarily and selectively affects serotonergic transmission.
Behavioral data in healthy controls with and without genetic risk for depression and in patient populations during the symptomatic phase of depression and at referral suggest an abnormality of serotonin function in depression and that antidepressants can compensate for the underlying deficit.
Tryptophan depletion may be a useful tool to build more integrative models of depression pathophysiology that account for neurobiological systems beyond monoamines. Recent studies combining tryptophan depletion with genetic variables may provide an important approach to studying gene/environment interactions using candidate genes to define endophenotypes, which will ultimately improve the diagnostic categories currently in use and help create more advanced models for understanding the neurobiology of depression.
This could lead to the development of truly novel treatment approaches for depression.
Tryptophan Depletion, Serotonin, and Depression: Where Do We Stand?