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The interactive association of adverse childhood experiences and polygenic susceptibility with depressive symptoms and chronic inflammation in older adults: a prospective cohort study

Published online by Cambridge University Press:  05 August 2021

Eleonora Iob*
Research Department of Behavioural Science and Health, Institute of Epidemiology and Healthcare, University College London, London, UK
Olesya Ajnakina
Research Department of Behavioural Science and Health, Institute of Epidemiology and Healthcare, University College London, London, UK Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
Andrew Steptoe
Research Department of Behavioural Science and Health, Institute of Epidemiology and Healthcare, University College London, London, UK
Author for correspondence: Eleonora Iob, E-mail:



Adverse childhood experiences (ACEs) and genetic liability are important risk factors for depression and inflammation. However, little is known about the gene−environment (G × E) mechanisms underlying their aetiology. For the first time, we tested the independent and interactive associations of ACEs and polygenic scores of major depressive disorder (MDD-PGS) and C-reactive protein (CRP-PGS) with longitudinal trajectories of depression and chronic inflammation in older adults.


Data were drawn from the English longitudinal study of ageing (N~3400). Retrospective information on ACEs was collected in wave3 (2006/07). We calculated a cumulative risk score of ACEs and also assessed distinct dimensions separately. Depressive symptoms were ascertained on eight occasions, from wave1 (2002/03) to wave8 (2016/17). CRP was measured in wave2 (2004/05), wave4 (2008/09), and wave6 (2012/13). The associations of the risk factors with group-based depressive-symptom trajectories and repeated exposure to high CRP (i.e. ⩾3 mg/L) were tested using multinomial and ordinal logistic regression.


All types of ACEs were independently associated with high depressive-symptom trajectories (OR 1.44, 95% CI 1.30–1.60) and inflammation (OR 1.08, 95% CI 1.07–1.09). The risk of high depressive-symptom trajectories (OR 1.47, 95% CI 1.28–1.70) and inflammation (OR 1.03, 95% CI 1.01–1.04) was also higher for participants with higher MDD-PGS. G×E analyses revealed that the associations between ACEs and depressive symptoms were larger among participants with higher MDD-PGS (OR 1.13, 95% CI 1.04–1.23). ACEs were also more strongly related to inflammation in participants with higher CRP-PGS (OR 1.02, 95% CI 1.01–1.03).


ACEs and polygenic susceptibility were independently and interactively associated with elevated depressive symptoms and chronic inflammation, highlighting the clinical importance of assessing both ACEs and genetic risk factors to design more targeted interventions.

Original Article
Copyright © The Author(s), 2021. Published by Cambridge University Press.

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