Steroid 21-hydroxylase gene variants and late-life depression.
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ABSTRACT: Objectives
A feature of late-life depression is alterations of the stress hormone system. The CYP21A2 gene encodes for the steroid 21-hydroxylase enzyme which is required for the biosynthesis of mineralocorticoids and glucocorticoids, two main components of the stress response in humans. Variants in the CYP21A2 gene could influence risk of late-life depression, but this has not been examined. This study investigated possible associations between five variants in the CYP21A2 gene and late-life depression in 1007 older community-dwelling men and women.Results
In multivariate logistic regression model, significant associations were found between three single-nucleotide polymorphisms (rs389883, rs437179, and rs630379) and depression in women specifically (OR ranging from 1.51 to 1.68, p-values 0.025 to 0.0045), and the two latter remained significant after correction for multiple testing. Variants of the CYP21A2 gene appear as susceptibility factors for late-life depression in a sex-specific manner, independently of somatic and neuropsychiatric comorbidity.
SUBMITTER: Ancelin ML
PROVIDER: S-EPMC8147346 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo identify cognitive phenotypes in late-life depression (LLD) and describe relationships with sociodemographic and clinical characteristics.DesignObservational cohort study.SettingBaseline data from participants recruited via clinical referrals and community advertisements who enrolled in two separate studies.ParticipantsNon-demented adults with LLD (n = 120; mean age = 66.73 ± 5.35 years) and non-depressed elders (n = 56; mean age = 67.95 ± 6.34 years).MeasurementsAll completed a neuropsychological battery, and individual cognitive test scores were standardized across the entire sample without correcting for demographics. Five empirically derived cognitive domain composites were created, and cluster analytic approaches (hierarchical, k-means) were independently conducted to classify cognitive patterns in the depressed cohort only. Baseline sociodemographic and clinical characteristics were then compared across groups.ResultsA three-cluster solution best reflected the data, including "High Normal" (n = 47), "Reduced Normal" (n = 35), and "Low Executive Function" (n = 37) groups. The "High Normal" group was younger, more educated, predominantly Caucasian, and had fewer vascular risk factors and higher Mini-Mental Status Examination compared to "Low Executive Function" group. No differences were observed on other sociodemographic or clinical characteristics. Exploration of the "High Normal" group found two subgroups that only differed in attention/working memory performance and length of the current depressive episode.ConclusionsThree cognitive phenotypes in LLD were identified that slightly differed in sociodemographic and disease-specific variables, but not in the quality of specific symptoms reported. Future work on these cognitive phenotypes will examine relationships to treatment response, vulnerability to cognitive decline, and neuroimaging markers to help disentangle the heterogeneity seen in this patient population.
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