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

Frank, P; Ajnakina, O; Steptoe, A; Cadar, D; (2020) Genetic susceptibility, inflammation and specific types of depressive symptoms: evidence from the English Longitudinal Study of Ageing. Translational Psychiatry , 10 (1) , Article 140. 10.1038/s41398-020-0815-9. Green open access

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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.

Type: Article
Title: Genetic susceptibility, inflammation and specific types of depressive symptoms: evidence from the English Longitudinal Study of Ageing
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41398-020-0815-9
Publisher version: https://doi.org/10.1038/s41398-020-0815-9
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Behavioural Science and Health
URI: https://discovery.ucl.ac.uk/id/eprint/10097232
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