In order to ascertain the extent of hypothalamo-pituitary-adrenal cortical (HPA) hyperactivity in endogenous depression, we determined circadian serum cortisol patterns, cortisol responses to dexamethasone (DEX) administration, and urine free cortisol excretion before and after DEX administration in 40 definite endogenous depressives diagnosed with the Research Diagnostic Criteria. The cortisol measures ranged from normal to clearly elevated. To elucidate the clinical correlates of these hormone measures in the patients, we examined the relationships of the pre- and post-DEX cortisol measures to the diagnosis of endogenous/melancholic depression by different systems and to the overall severity and specific dimensions of depressive symptomatology.
In this group of endogenous depressives, none of the diagnostic schemes for endogenous/melancholic depression which we studied was significantly related to the pre- or post-DEX cortisol measures. Of the other subject and symptom variables, only age and the agitation/anxiety factor of the Hamilton depression scale showed consistent relationships with the cortisol measures. Both were positively correlated, to a moderate degree, with the hormone measures, and they were not correlated with each other. Together they explained approximately 20% of the variance in the cortisol measures. Thus, within a group of moderately to severely ill endogenous depressives, the older and the more agitated anxious patients have a significantly greater likelihood of showing increased HPA activity. These findings indicate that age should be controlled in studies of the HPA axis and that the subjective experience of anxiety may contribute to HPA hyperactivity in endogenous depression.