A Neuroendocrine Study of 5HT Function in Depression: Evidence for Biological Mechanisms of Endogenous and Psychosocial Causation

To investigate whether depression is a consequence of disturbed function in 5HT systems, neuroendocrine responses to infusions of the 5HT precursor L-tryptophan (LTP) were studied in patients and controls. After an overnight fast and 60 min bed rest, a solution of LTP (10 g/l) was infused intravenously to a dose of 100 mg/kg over 30 min. Circulating growth hormone (GH), prolactin (PRL), cortisol and tryptophan concentrations were followed from 60 min pre-infusion to 60 min post-infusion. GH responses were attenuated in 23 major depressives (DSM-III) compared with 22 controls and were almost absent in endogenous depressives (New-castle criteria). PRL responses were normal in depressives who had lost more than 3 kg body weight but attenuated in those who had not. GH and PRL responses did not correlate with each other. Reduced basal tryptophan concentrations and more rapid tryptophan clearance were observed in the depressives, but there were no correlations with GH or PRL responses. However, basal cortisol concentrations, which were raised in depressives with chronic psychosocial difficulties, were strongly and inversely predictive of PRL responses in depressives and controls. Blunted GH and PRL responses to LTP appear to be distinct abnormalities in depression which may relate to two processes; (1), an endogenous mechanism indicated by reduced GH responses, and (2), an impairment in 5HT systems, indicated by blunted PRL responses and perhaps caused by raised circulating cortisol or reduced tryptophan concentrations.