Diurnal variations in endocrine and psychological responses to 0.2 mg/kg naloxone administration in patients with major depressive disorder and matched controls

Background: There is evidence that the endogenous opioid system (EOS) is involved in the modulation of mood and neuroendocrine function. Furthermore, the possible involvement of the EOS in major depression has been postulated, although a clear role has not been established. Methods: The affective and endocrine responses to naloxone administration in seven female depressives and in seven matched controls and their diurnal variations were investigated. Subjects had an i.v. bolus of either 0.2 mg/kg naloxone or saline at two time points (09:00 or 18:00 h) and for 2 days in a single-blind, cross-over design. Results: The basal cortisol plasma levels, both in the morning and in the afternoon, showed higher values (P<0.05) in the depressives. There was a naloxone-induced increase in the adrenocorticotrophic hormone (ACTH), cortisol, and luteinizing hormone (LH) plasma levels, plus a subjective dysphoric effect in both groups. The depressives showed a greater dysphoric effect both in the morning and afternoon (P<0.05), and a blunted cortisol response in the afternoon (P<0.05). There were no differences between groups or time of day in the ACTH or LH responses. Limitations: The sample size was small, but by studying each patient as their own control, plus a matched control for every patient, softens this effect. Finding patients with a major depressive episode free of medication is difficult, and this aspect contributes to the size of the sample. Conclusions: These results suggest that opioid mechanisms may be involved in the HPA axis changes and possibly in mood changes found in depression. The discrepancy between increased sensitivity in depression to mood changes and decreased change in cortisol may indicate a ceiling effect for the latter.