ARE DHEA AND/OR DHEA-S CONCENTRATIONS ASSOCIATED WITH REMISSION OF DEPRESSION OR IMPROVEMENTS IN MENTAL STATUS SCORES IN OLDER ADULTS?

Abstract

Purpose: DHEA and DHEA-S concentrations decline with advancing age and are thought to be related to mood and cognitive function. Recently, the authors reported that alprazolam-induced acute increases in DHEA concentrations were associated with improved psychomotor function. Others have reported low morning concentrations of DHEA in adolescents and adults diagnosed with depression. Therefore, the authors evaluated DHEA and DHEA-S concentrations in an ongoing double-blind comparative trial of antidepressants in older depressed adults. A secondary purpose was to evaluate concentrations of these steroids relative to cognitive function of these depressed patients. Methods: Subjects were 40 in- and out-patients (8 men, 32 women; 63 to 88 years of age) who met DSM-IV criteria for major depression and who were enrolled in a 12-week, double-blind treatment study at the University of Pittsburgh. Ten patients were cognitively impaired based on their Mattis Dementia Rating Scale score (MDRS), but did not meet NINCDS-ADRDA criteria for a diagnosis of probable or possible Alzheimer's disease or DSM-IV criteria for dementia. Subjects underwent thorough medical, psychiatric and cognitive assessments at week 0, which was prior to randomization to 12 weeks of treatment with either nortriptyline (n=17) or paroxetine (n=23). All 40 subjects experienced remission of depression symptoms following 12 weeks of either nortriptyline or paroxetine, as indicated by Ham-D scores at Week 0 (22.4) and at Week 12 (6.7; P<0.001). Global Assessment of Functioning (GAF) scores were 45.3 at Week 0 and 76.2 at Week 12 (P<0.001). The Folstein MMSE and the MDRS were assessed at Week 0 and after 12 weeks of treatment. For analysis of steroid concentrations, morning blood samples were obtained at Week 0, and at 6 and 12 weeks. Serum samples were assayed for DHEA, DHEA-S, and cortisol using an 125I-radioimmunoassay method. Results: The differences between pre- and post-treatment scores on both Ham-D and GAF were significant (P<0.001), reflecting the successful treatment of depressed mood and consequent gain in functioning. At Week 0, the range of concentrations was wide for DHEA (0.6 1/n – 17.2 ng/ml), DHEA-S (41.0–4116 ng/ml), and cortisol (2.1–34.6 μg/dl). Mean DHEA and DHEA-S concentrations decreased with the remission of depression, as indicated in Table 1, although increases relative to Week 0 were observed in some subjects at Week 6 (DHEA, n=10; DHEA-S, n=11), and Week 12 (DHEA, n=5; DHEA-S, n=8). There were no differences in DHEA or DHEA-S concentrations between the nortriptyline and paroxetine treatment groups. There was a significant correlation between the change in cortisol and change in GAF score from Week 0 and Week 12 (P=0.01). The cognitively impaired (CI) patients tended to have higher DHEA and DHEA-S concentrations at Week 0 than the nonimpaired group (NI) (P>0.2). During therapy, the decreases in concentrations also tended to be greater in the CI group; the change from Week 0 at Weeks 6 and 12, respectively, expressed as CI:NI ratios of the means were 0.75 and 1.5 (DHEA), 1.6 and 1.2 (DHEA-S), and 2.2 and 32.3 (cortisol). There were no correlations between cognitive and psychosocial functioning and concentrations of DHEA or DHEA-S. Conclusions: Data from these older depressed patients indicate that DHEA and DHEA-S concentrations decrease during successful treatment with nortriptyline or paroxetine. Mean DHEA and DHEA-S concentrations decreased within 6 weeks of therapy, remained relatively unchanged through 12 weeks of treatment, and were independent of drug treatment group. Whether the changes in hormone concentrations are a consequence of remission of depression or of a specific drug effect cannot be determined. In the subset of 10 CI patients, no significant correlation was identified between the changes in either DHEA or DHEA-S concentrations and improvement in cognitive function assessed by the MDRS. The decrease in DHEA and DHEA-S concentrations in the majority of subjects was not anticipated. The source of variability in DHEA and DHEA-S concentrations in response to remission from depression needs to be further evaluated. P38