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

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.

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.

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.

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.

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.