Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans

Measurement of melatonin secretion throughout the night provides an index of net noradrenergic activity mediated by postsynaptic beta-adrenergic receptors in the pineal gland. Reduced melatonin secretion in some patients with depression might be related to reduced net noradrenergic function. However, a dysregulation in serotonin function has also been implicated in the pathophysiology of depression. The essential amino acid tryptophan is the precursor for both serotonin and melatonin production. To determine the effects of serotonin function on nocturnal melatonin secretion, eight healthy volunteers underwent active and sham tryptophan depletion in a randomized, double-blind fashion. Blood samples for melatonin and free and total tryptophan were obtained before and after the depletion. Acute tryptophan depletion decreased free and total plasma tryptophan levels to less than 20% of baseline levels. Melatonin secretion, expressed as area under the curve, was decreased in all eight subjects after tryptophan depletion when compared to sham depletion. These results suggest that reduced plasma tryptophan levels, and presumably brain serotonin concentrations, decrease nocturnal melatonin secretion in humans. Additional studies investigating the relationship between serotonin metabolism and pineal function in humans appear warranted.