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

Philipp Frank,Andrew Steptoe,Olesya Ajnakina,Dorina Cadar

doi:10.1038/s41398-020-0815-9

Philipp Frank, Andrew Steptoe + Show 2 more

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https://doi.org/10.1038/s41398-020-0815-9

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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.

Highlights

Depression is a leading cause of disability and a growing public health concern worldwide, among older adults[1,2]
Confirmatory factor analysis (CFA) confirmatory factor analysis (CFA) of the items included in the Centre for Epidemiological Studies Depression Scale (CES-D) 8 indicated that the two-factor model differentiating between cognitiveaffective and somatic symptoms fit the data better than the one-factor model (Supplementary Fig. S1)
This is the first study to investigate the prospective associations between genetic susceptibility to depressive symptomatology, systemic low-grade inflammation (i.e., C-reactive protein (CRP)) and specific types of depressive symptoms in a large nationally representative cohort of older adults

Summary

Introduction

Depression is a leading cause of disability and a growing public health concern worldwide, among older adults[1,2]. It is typically characterised by a number of cognitive, affective and somatic symptoms, including anhedonia, low mood, loss of appetite, and sleep problems[3]. According to a previous prevalence study, ~18% of adults aged 65 years and older in England experience elevated depressive symptoms[4]. Research indicates that depression has substantial public health implications. Research has attempted to uncover plausible biopsychosocial pathways contributing to the development of depression. The exact biological, psychological and social mechanisms underlying the pathogenesis of depression remain elusive

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