Effects of glucocorticoids on declarative memory function in major depression

Background: Major depression has been associated with hypercortisolemia in a subset oJpatients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects bas been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexametbasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). Methods: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or daxamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memon, was assessed with paragraph recall at baseline (day 1) and day 3. Results: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3 Conclusions: These findings are consistent with an altered sensitivity of declarativc memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethazone-induced reductions in cortisol, in patients with MDD.