Elevated prolactin responses to L-tryptophan infusion in medication-free depressed patients

Abstract

Rationale: Several previous neuroendocrine studies have demonstrated reduced 5-HT1A receptor function in major depressive disorder (MDD). However, hypercortisolaemia or previous drug treatment may have been significant confounds.

Objectives: To replicate previous studies in subjects with MDD who had been drug free for at least 8 weeks and to relate the findings to measures of HPA axis function.

Methods: Hormonal responses to l-tryptophan infusion were measured in patients with MDD (n=20) and healthy controls (n=20). Basal salivary cortisol and DHEA were also profiled.

Results: No attenuation of 5-HT1A receptor-dependent neuroendocrine responses (growth hormone, prolactin) was observed in patients with MDD. The prolactin response to l-tryptophan was significantly greater in MDD patients than in healthy controls (P=0.008). There was a significant negative correlation between prolactin response and basal salivary cortisol secretion over the 3 days prior to the test.

Conclusions: These data do not support previous findings of reduced 5-HT1A function in MDD and suggest that hypercortisolaemia or psychotropic medication may have accounted for the attenuation. Basal cortisol, DHEA and the cortiso l-DHEA ratio did not differ between patients and controls, and all patients were psychotropic medication-free. The greater prolactin response to l-tryptophan infusion in depressed subjects may be the result of an increase in dopamine receptor sensitivity, secondary to reduced dopamine levels.