The ratio of cortisol/DHEA in treatment resistant depression

OBJECTIVE: Hypercortisolaemia has been well described in depression and may be a factor associated with treatment resistance. The role of the more abundant adrenal steroid dehydroepiandrosterone (DHEA) has been recently investigated, with some evidence that it may have an antiglucocorticoid effect. This study measured cortisol, DHEA and their ratio in treatment resistant depression (TRD) and healthy controls and also related these measures to treatment outcome. METHOD: Plasma cortisol, DHEA and cortisol/DHEA ratio were determined at 0900h in 28 patients with TRD and 40 healthy controls. The measures were repeated following inpatient treatment in a subgroup of 21 patients and related to the outcome of such treatment. The stability of cortisol/DHEA ratios was assessed with 2 hourly samples from 0900 to 1700h in a subgroup of 15 controls. RESULTS: Basal levels of cortisol and the cortisol/DHEA ratio were higher in patients compared to controls. Whilst cortisol levels were lower after treatment, there was no relationship between cortisol levels and treatment outcome. In contrast, treatment responders had significantly lower DHEA on admission and a higher cortisol/DHEA ratio both on admission and on discharge. Cortisol/DHEA ratios were stable between 9 a.m. and 5 p.m. CONCLUSIONS: In addition to cortisol, the cortisol/DHEA ratio is raised in TRD; thus, there is no evidence that DHEA levels could negate the increased glucocorticoid activity in TRD. Patients with a more abnormal cortisol/DHEA ratio, possibly indicating greater biological dysfunction, responded preferentially to inpatient therapy, though the raised cortisol/DHEA ratio persisted after response. The cortisol/DHEA ratio is stable throughout the day and may be a more practical biological marker of TRD.