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Genetic susceptibility, inflammation and specific types of depressive symptoms: evidence from the English Longitudinal Study of Ageing.

ABSTRACT: Genetic susceptibility to depression has been established using polygenic scores, but the underlying mechanisms and the potentially differential effects of polygenic scores on specific types of depressive symptoms remain unknown. This study examined whether systemic low-grade inflammation mediated the association between polygenic scores for depressive symptomatology (DS-PGS) and subsequent somatic versus cognitive-affective depressive symptoms. The sample consisted of 3510 men and women (aged 50+) recruited from the English Longitudinal Study of Ageing. DS-PGS were derived using the results of a recent genome-wide association study. Plasma C-reactive protein (CRP) was measured at wave 6 (2012/13). Depressive symptoms were assessed at wave 8 (2016/17), using the eight-item version of the Centre for Epidemiological Studies Depression Scale. Covariates (wave 2, 2004/05) included age, sex and ten principal components (PCs) to control for population stratification. Confirmatory factor analysis was performed to corroborate a previously identified two-factor structure of the CES-D, distinguishing between cognitive-affective and somatic symptoms. Longitudinal structural equation modelling was used to investigate the mediating role of CRP in the relationship between DS-PGS and cognitive-affective versus somatic symptoms. Our results showed that participants with a higher polygenic susceptibility to DS were significantly more likely to report cognitive-affective and somatic symptoms at follow-up. Mediation analyses revealed that CRP mediated the relationship between DS-PGS and somatic symptoms, but not the association between DS-PGS and cognitive-affective symptoms. These differential effects highlight the importance of considering individual differences in depression profiles in future studies. Ultimately, this will inform healthcare professionals to design more targeted treatments.

SUBMITTER: Frank P

PROVIDER: S-EPMC7217832 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Genetic susceptibility, inflammation and specific types of depressive symptoms: evidence from the English Longitudinal Study of Ageing.

Frank Philipp P Ajnakina Olesya O Steptoe Andrew A Cadar Dorina D

Translational psychiatry 20200512 1

Genetic susceptibility to depression has been established using polygenic scores, but the underlying mechanisms and the potentially differential effects of polygenic scores on specific types of depressive symptoms remain unknown. This study examined whether systemic low-grade inflammation mediated the association between polygenic scores for depressive symptomatology (DS-PGS) and subsequent somatic versus cognitive-affective depressive symptoms. The sample consisted of 3510 men and women (aged 5 ...[more]

PMID: 32398645

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Project description:BackgroundDepressive symptoms and physical performance are inversely associated, but it is unclear whether their association is bidirectional. We examined whether the association between depressive symptoms and physical performance measured using gait speed is bidirectional.MethodsWe used a national sample of 4,581 community-dwelling people aged 60 years and older from the English Longitudinal Study of Ageing (from 2002-03 to 2008-09). We fitted Generalized Estimating Equation (GEE) regression models to analyse repeated measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a score of ?4 on the eight-item Center for Epidemiological Studies-Depression scale).ResultsSlower gait speed was associated with elevated depressive symptoms both concurrently and two years later. After adjustment for previous depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and cognitive factors the concurrent association was partially explained (Odds Ratio [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to 1.00). Elevated depressive symptoms were associated with slower gait speed. Full adjustment for covariates (including previous gait speed) partially explained both the concurrent (? regression coefficient [?] -0.038, 95% CI, -0.050 to -0.026, for participants with elevated depressive symptoms compared with those with no or one symptom) and the two-year lagged associations (? -0.017, 95% CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of two or three on the eight-item Center for Epidemiological Studies-Depression scale) were also associated with slower gait speed. Full adjustment for covariates partially explained both the concurrent (? -0.029, 95% CI, -0.039 to -0.019, for participants with subthreshold symptoms compared with those with no or one symptom) and the two-year lagged associations (? -0.011, 95% CI, -0.021 to -0.001).ConclusionsThe inverse association between gait speed and depressive symptoms appears to be bidirectional.

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Genetic susceptibility, inflammation and specific types of depressive symptoms: evidence from the English Longitudinal Study of Ageing.

Publications

Genetic susceptibility, inflammation and specific types of depressive symptoms: evidence from the English Longitudinal Study of Ageing.

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