Higher serum dehydroepiandrosterone sulfate protects against the onset of depression in the elderly: Findings from the English Longitudinal Study of Aging (ELSA)

Souza-Teodoro, Luis Henrique; Oliveira, César de; Walters, Kate; Carvalho, Lívia A.

doi:10.1016/j.psyneuen.2015.11.005

Cited by 31 publications

(40 citation statements)

References 65 publications

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“…Our findings are consistent with the results of some prospective studies, suggesting an association of lower DHEAS levels with depression . Also, a recent study found that higher DHEAS levels were associated with reduced risk of developing depressive symptoms . This is consistent with results of controlled trials of DHEA therapy which have reported significant positive effects on mood .…”

Section: Discussionsupporting

confidence: 92%

Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in combat veterans with or without a history of suicide attempt

Sher

Flory

Bierer

et al. 2018

Acta Psychiatr Scand

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Section: Discussionsupporting

confidence: 92%

Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in combat veterans with or without a history of suicide attempt

Sher

Flory

Bierer

et al. 2018

Acta Psychiatr Scand

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“…This suggests a dysregulation of endogenous production of DHEA and DHEAS in the brain in MDD. Indeed, lower DHEA in women during peri‐menopause and lower DHEAS concentration in both elderly men and women in plasma have been found to be related to higher depression symptoms and a higher prevalence of depression, while higher serum DHEAS significantly reduced the risk of developing depressive symptoms . It should be noted though that conflicting findings also exist , possibly due to differences in study design.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

Luchetti

Verwer

et al. 2017

Brain Pathology

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Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC). In order to determine whether the endogenous production of steroids is altered in the ACC and DLPFC of patients with major depressive disorder (MDD) or bipolar disorder (BPD), quantitative real-time PCR was performed to detect mRNA expression level of key enzymes in the steroid biosynthetic pathways. In MDD, a significant decrease in mRNA level of cytochrome P450 17A1 (CYP17A1, synthesizing C19 ketosteroids) in the ACC and a significant increase in mRNA levels of hydroxysteroid sulfotransferase 2A1 [SULT2A1, catalyzing the sulfate conjugation of dehydroepiandrosterone (DHEA)] were observed in the DLPFC, suggesting alterations in DHEA and its sulfate metabolite DHEAS levels. Decreased intensity and distribution of CYP17A1 immunohistochemical staining was found in the ACC of MDD patients. Interestingly, there was a significant positive correlation between the mRNA levels of CYP17A1 and tyrosine-related kinase B (TrkB) full length isoform. In a unique post-mortem human brain slice culture paradigm, BDNF mRNA expression was found to be significantly increased following incubation with DHEA. Together, these data indicate a close relationship between DHEA and BDNF-TrkB pathways in depression. Furthermore, in the DLPFC, higher mRNA levels of 11β-hydroxysteroid dehydrogenase-1 (HSD11B1, reducing cortisone to the active hormone cortisol) and steroidogenic acute regulatory protein (STAR, facilitating the shuttle of cholesterol through the intermembrane space) were found in the MDD patients and BPD patients, respectively. In conclusion, this study suggests the presence of a disturbance in the endogenous synthesis of DHEA and DHEAS in mood disorders, which has a close relationship with BDNF-TrkB signaling.

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“…Detailed information on the technicalities of the blood analysis, the internal quality control and the external quality assessment for the laboratory have been described elsewhere 18. Dehydroepiandrosterone (DHEA(S)) levels from serum was performed using the Roche DHEA(S) assay that is a competitive immunoassay using electrochemiluminescence technology (analytical range: 0.003–27 μmol/L) 19. Haemoglobin level (g/L) was measured with two Abbott Diagnostics Cell-Dyn 4000 analysers 20.…”

Section: Methodsmentioning

confidence: 99%

The structure and predictive value of intrinsic capacity in a longitudinal study of ageing

et al. 2019

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ObjectivesTo assess the validity of the WHO concept of intrinsic capacity in a longitudinal study of ageing; to identify whether this overall measure disaggregated into biologically plausible and clinically useful subdomains; and to assess whether total capacity predicted subsequent care dependence.DesignStructural equation modelling of biomarkers and self-reported measures in the English Longitudinal Study of Ageing including exploratory factor analysis, exploratory bi-factor analysis and confirmatory factor analysis. Longitudinal mediation and moderation analysis of incident care dependence.SettingsCommunity, United Kingdom.Participants2560 eligible participants aged over 60 years.Main outcome measuresActivities of daily living (ADL) and instrumental activities of daily living (IADL).ResultsOne general factor (intrinsic capacity) and five subfactors emerged: locomotor, cognitive; psychological; sensory; and ‘vitality’. This structure is consistent with biological theory and the model had a good fit for the data (χ2=71.2 (df=39)). The summary score of intrinsic capacity and specific subfactors showed good construct validity. In a causal path model examining incident loss of ADL and IADL, intrinsic capacity had a direct relationship with the outcome—root mean square error of approximation (RMSEA)=0.02 (90% CI 0.001 to 0.05) and RMSEA=0.008 (90% CI0.001 to 0.03) respectively—and was a strong mediator for the effect of age, sex, wealth and education. Multimorbidity had an independent direct relationship with incident loss of ADLs but not IADLs, and also operated through intrinsic capacity. More of the indirect effect of personal characteristics on incident loss of ADLs and IADLs was mediated by intrinsic capacity than multimorbidity.ConclusionsThe WHO construct of intrinsic capacity appears to provide valuable predictive information on an individual’s subsequent functioning, even after accounting for the number of multimorbidities. The proposed general factor and subdomain structure may contribute to a transformative paradigm for future research and clinical practice.

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Higher serum dehydroepiandrosterone sulfate protects against the onset of depression in the elderly: Findings from the English Longitudinal Study of Aging (ELSA)

Abstract: HighlightsDHEA-S levels is inversely correlated with depressive symptoms at baseline.Chronic illnesses and health behaviors abolish the association between DHEA-S and depression at baseline.Low levels of DHEA-S at baseline predict depression at 4-year follow up.

Cited by 31 publications

References 65 publications

Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in combat veterans with or without a history of suicide attempt

Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in combat veterans with or without a history of suicide attempt

Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: A post‐mortem study

The structure and predictive value of intrinsic capacity in a longitudinal study of ageing

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