Background. An investigation of the association between diurnal changes in cortisol and DHEA levels, or in the cortisol/DHEA ratio at five different time points at presentation, and the occurrence of undesirable life events (losses, dangers to self and others, disappointments) during follow-up, and the outcome of major depression at 36 weeks were investigated.

Methods. Psychosocial and endocrine assessment of a consecutive cohort (N=68) of 8- to 16-year-old subjects with first episode major depression reassessed 12 months after presentation using a repeat measures design.

Results. Higher cortisol/DHEA ratios at 20.00 or 24.00 h predicted persistent major depression. Basal levels of either hormone alone or cortisol/DHEA ratios at the other three time points (08.00, 12.00 or 16.00 h) did not. High cortisol/DHEA ratios (i.e. values greater than the 60th percentile) at both evening points (20.00 and 24.00 h) also predicted the occurrence of subsequent disappointing life events but no other category of undesirable event. Both high evening cortisol/DHEA ratio at 20.00 h and one or more severely disappointing life events between presentation and follow-up predicted persistent major depression: 86% of subjects with both of these factors were still depressed at 36 weeks whereas 81% with neither factor were not.

Conclusions. The finding that it is depressed subjects with high cortisol/DHEA ratios at presentation who are specifically at risk for subsequent disappointing life events suggests a putative role for these adrenal steroids in abnormal cognitive or emotional processes associated with disturbed interpersonal behaviour.