Effects of glucocorticoids on declarative memory function in major depression.
BACKGROUND
Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has 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, dexamethasone, 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 dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory 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 declarative 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 dexamethasone-induced reductions in cortisol, in patients with MDD.
Bremner
J Douglas
JD
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 126 Briarcliff Road, Atlanta, GA 30306, USA.
Vythilingam
Meena
M
Vermetten
Eric
E
Anderson
George
G
Newcomer
John W
JW
Charney
Dennis S
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D014706:Verbal Learning / Q000187:drug effects*
D005938:Glucocorticoids; D003907:Dexamethasone; D006854:Hydrocortisone