Regular Research ArticleSerum Dehydroepiandrosterone Sulfate and Incident Depression in the Elderly: The Pro.V.A. Study
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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Cited by (22)
Could dehydroepiandrosterone (DHEA) be a novel target for depression?
2022, Journal of Affective Disorders ReportsCitation Excerpt :The opposite was also observed, i.e. reduced DHEA(S) levels were associated to further development of depression (1-year follow-up) only in men, amongst Japanese (Michikawa et al., 2013) and Taiwanese (Goldman and Glei, 2007) cohorts with both genders (3 years follow-up) Veronese et al. (2015). showed an inverse association with depression in both men and women (4.4 years follow-up), but the severity of depression was associated to DHEA(S) levels only in men (Veronese et al., 2015). The largest study to date of a community-dwelling of men and women shows DHEA(S) is a predictor (4 years follow-up) of depression in both genders (Souza-Teodoro et al., 2016).
Risk factors of late life depression in the elderly: A systematic review
2021, Psiquiatria BiologicaDo dehydroepiandrosterone, progesterone, and testosterone influence women's depression and anxiety levels? Evidence from hair-based hormonal measures of 2105 rural Indian women
2019, PsychoneuroendocrinologyCitation Excerpt :Research in human populations is less conclusive. Among men, despite conflicting evidence across clinical populations and cohort studies (Asselmann et al., 2019; Heald et al., 2017; Kische et al., 2017; T’sjoen et al., 2005; Wu et al., 2010), increasing evidence suggests that higher sex hormone levels are associated with lower depressive symptoms (Almeida et al., 2008; Barrett-Connor et al., 1999b; Ford et al., 2016; Kische et al., 2018; Korenman et al., 2018; Veronese et al., 2015; Walther et al., 2016; Westley et al., 2015). For women, study results are more conflicting and report anywhere from no associations (Asselmann et al., 2019; Giltay et al., 2017) to both positive and negative associations with depression.
Dehydroepiandrosterone sulfate and fall risk in older people: Sex differences in the Pro.V.A. longitudinal study
2019, MaturitasCitation Excerpt :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.
Steroid secretion in healthy aging
2019, PsychoneuroendocrinologyCitation Excerpt :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).