Positron emission tomography study of the effects of tryptophan depletion on brain serotonin(2) receptors in subjects recently remitted from major depression.

CONTEXT Decreased brain serotonin (5-hydroxytryptamine) levels are considered to mediate depressive relapse induced by the tryptophan depletion paradigm. However, in patients who recently achieved remission from a major depressive episode with antidepressant treatment, only about half become depressed following tryptophan depletion. We hypothesized that downregulation of brain serotonin(2) receptors might be a compensatory mechanism that prevents some patients from becoming depressed with tryptophan depletion. OBJECTIVE To assess, with use of positron emission tomography, whether brain serotonin(2) receptor downregulation occurs in patients with recently remitted depression who do not have depressive relapse, but not in those who become depressed, following tryptophan depletion. DESIGN Each patient underwent 2 fluorine 18-labeled- setoperone positron emission tomography scans, one following a tryptophan depletion session and another following a control session. The order of scanning was counterbalanced. SETTING Academic university hospital with imaging facilities. PARTICIPANTS Seventeen patients in recent remission from a DSM-IV major depressive episode following treatment with selective serotonin reuptake inhibitors. MAIN OUTCOME MEASURES Changes in brain serotonin(2) receptor binding. RESULTS Of the 17 patients, 8 (47%) became depressed during the tryptophan depletion session, and none developed depression during the control session. The depletion session was associated with a significant reduction in brain serotonin(2) receptor binding compared with the control session for all participants. A subgroup analysis revealed that the reduction in serotonin(2) receptor binding was significant only for the nondepressed group. CONCLUSION Reduction in brain serotonin(2) receptors might be a potential compensatory mechanism to prevent tryptophan depletion-induced depressive relapse.