Regular Research Article
Serum Dehydroepiandrosterone Sulfate and Incident Depression in the Elderly: The Pro.V.A. Study

https://doi.org/10.1016/j.jagp.2014.10.009Get rights and content

Objective

Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but contrasting findings are available. Therefore, we investigated whether high serum DHEAS levels were associated with any protective effect on incident depression and incident severe depression in a representative group of elderly men and women.

Methods

In a population-based cohort longitudinal study in the general community, 789 older participants without depression and cognitive impairment at the baseline were included, among 3,099 screened subjects. Serum DHEAS levels were determined based on blood samples; incident depression and severe depression were diagnosed by means of the Geriatric Depression Scale (GDS) and confirmed by geriatricians skilled in psychogeriatric medicine.

Results

No baseline differences were found in GDS across age- and gender-specific tertiles of serum DHEAS. Over 4.4 years of follow-up, 137 new cases of depression were recorded. Of them, 35 among men and 64 in women were cases of incident severe depression. Cox's regression analysis, adjusted for potential confounders, revealed that higher DHEAS levels were associated with reduced risk of incident depression irrespective of gender (HR: 0.30; 95% CI: 0.09–0.96; Wald χ2 = 4.09; df = 1; p = 0.04; women: HR: 0.31; 95% CI: 0.14–0.69; Wald χ2 = 8.37; df = 1; p = 0.004) and of severe incident depression only in men (HR: 0.25; 95% CI: 0.06–0.99; Wald χ2 = 4.05; df = 1; p = 0.04).

Conclusion

Higher serum DHEAS levels were found to be significantly protective for the onset of depression irrespective of gender, whereas only in men was this association found also for incident severe depression.

Introduction

Depression is widespread among elderly people, with a prevalence from 0.9% to 9.4% in community-dwelling people and higher in other settings like hospitals, nursing homes, and institutions.1 The presence of depression, particularly if severe, is strongly associated with disability, increased mortality, and poorer outcomes from physical illness.2

Research has shown that among possible factors affecting mood in the elderly, serum dehydroepiandrosterone sulfate (DHEAS) could be relevant. DHEAS is a sex steroid hormone mainly secreted by the adrenal glands but also in small amounts by the brain, where receptors for this hormone have selectively been found.3, 4, 5 DHEAS antidepressant and anxiolytic effects seem to be related to the agonistic activity on the σ-1 receptor,6 the inhibition of γ-aminobutyric acid A receptor directly and by decreasing pregnenolone-sulfate concentrations in the brain,7 the activation of N-methyl-d-aspartate receptor,7, 8, 9, 10, 11 and the up-regulation of brain-derived neurotrophic factor levels.12

Contrasting results have been reported in cross-sectional studies about the association between serum DHEAS levels and depression, particularly in females.13, 14, 15, 16, 17 At the same time, only a few longitudinal studies have investigated the protective association of high serum DHEAS levels for depressive symptoms in older adults. Two of these studies found a significant association only in men, whereas another two failed to find any relationship.5, 18, 19, 20 Finally, to the best of our knowledge, no study about DHEAS and incident severe depression are available, but this topic may be relevant because older people with severe depression have the highest suicide rate of any age group and a poorer prognosis of survival compared with younger subjects.21 The aim of the present study was thus to examine whether high serum DHEAS levels were associated with any protective effect on incident depression and incident severe depression and the possible role of gender in a representative group of elderly men and women over a lengthy follow-up (4.4 years).

Section snippets

Data Source and Subjects

Data for this analysis came from the Progetto Veneto Anziani (Pro.V.A.), an observational cohort study on the Italian population aged ≥65 years. Our study population included 3,099 age- and sex-stratified white participants (1,854 women and 1,245 men) randomly selected between 1995 and 1997 using a multistage stratified method. Sampling procedures and data collection methods are described elsewhere.22 Trained physicians and nurses examined participants at various clinics. The present study

Results

The sample consisted of 789 community-dwelling subjects over age 65 years (357 men and 432 women) without depression and cognitive impairment at baseline. Mean ages were 73.2 ± 6.5 for men and 72.9 ± 5.1 years for women. Mean DHEAS levels in men were significantly higher than in women (independent samples t test; 2.93 ± 1.96 μmol/L in men versus 1.66 ± 1.26 μmol/L in women; df = 787; t = 11.003; p <0.0001). Moreover, a Cox's regression analysis showed a significant interaction sex by baseline

Discussion

Our large population-based prospective study found that higher serum DHEAS levels reduced the risk of incident depression over a 4.4-year follow-up in both genders, whereas the association with severe depression was found only in men. The few existing studies about this topic gave contrasting results. Two studies, in fact, did not find any association between serum DHEAS levels and risk of depression,5, 30 whereas another two studies found an association only in men.18, 20 The differences

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      For participants ≤75 years (75 years was the median age of our sample), the tertile values were 1.90 and 3.40 μmol/L for men, and 0.90 and 1.90 μmol/L for women; for participants >75 years, the tertile values were 1.30 and 2.50 μmol/L in men, and 0.80 and 1.70 μmol/L in women. DHEA-S was preferred to DHEA because it shows little circadian, monthly or seasonal variation, making it more reliable as an epidemiologic marker [18]. Definition of outcome.

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      Since testosterone is a down-stream product of DHEA, studies have investigated the effect of DHEA and its sulfate DHEA-S on depressive symptoms, with conflicting findings. Some studies reported a protective effect of higher baseline DHEA-S levels on the onset of depressive symptoms (Souza-Teodoro et al., 2016; Veronese et al., 2015) or a positive association of DHEA-S with depressive symptoms but not with a diagnosis of major depression (Morrison et al., 2011). However, other longitudinal studies did not find an association (Bromberger et al., 2010; Dennerstein et al., 2002).

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