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Longitudinal associations between adolescents’ individualised risk for depression and inflammation in a UK cohort study

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Rachel Latham, Christian Kieling, Louise Arseneault, Brandon A Kohrt, Terrie Moffitt, Line Jee Hartmann Rasmussen, Thiago Rocha, Valeria Mondelli, Helen Fisher

Original languageEnglish
Pages (from-to)78-83
Number of pages6
JournalBrain Behavior and Immunity
Early online date3 Jan 2022
Accepted/In press29 Dec 2021
E-pub ahead of print3 Jan 2022
PublishedMar 2022

Bibliographical note

Funding Information: The E-Risk Study is funded by the Medical Research Council (UK MRC) [G1002190]. Additional support was provided by the US National Institute of Child Health and Human Development (NICHD) [HD077482]; the Jacobs Foundation, Switzerland; the King’s Together Multi and Interdisciplinary Research Scheme (UK Wellcome Trust Institutional Strategic Support Fund [204823/Z/16/Z]); UK MQ Transforming Mental Health Charity, Brighter Futures grant named “Identifying Depression Early in Adolescence” [MQBF/1 IDEA]; plus the UK MRC [MC_PC_MR/R019460/1] and the UK Academy of Medical Sciences [GCRFNG\100281] under the Global Challenges Research Fund. Helen L. Fisher and Rachel M. Latham are supported by the UK Economic and Social Research Council (ESRC) Centre for Society and Mental Health at King’s College London [ES/S012567/1]. Louise Arseneault is the Mental Health Leadership Fellow for the UK ESRC. Valeria Mondelli was part funded by the UK National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Christian Kieling has received support from Brazilian governmental research funding agencies (Conselho Nacional de Desenvolvimento Científico e Tecnológico [477129/2012-9 and 445828/2014-5], Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [62/2014], and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul [17/2551-0001009-4], Brazil) and is a UK Academy of Medical Sciences Newton Advanced Fellow. Brandon Kohrt has received support from the US National Institute of Mental Health (NIMH) [R01MH120649]. Line J. H. Rasmussen is supported by an international postdoctoral fellowship from the Lundbeck Foundation in Denmark [R288-2018-380]. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, the Department of Health and Social Care, the ESRC or King’s College London. These funders played no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit this article for publication. Publisher Copyright: © 2021 The Author(s)

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Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity – a risk factor for MDD – becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigation of the links between individuals’ constellation of MDD risk and subsequent inflammation. We therefore examined associations between individual risk for MDD calculated in early adolescence and levels of inflammation six years later. We use data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative UK birth cohort of 2,232 children followed to age 18 with 93% retention. Participants’ individual risk for developing future MDD was calculated at age 12 using a recently developed prediction model comprising multiple psychosocial factors. Plasma levels of three inflammation biomarkers were measured at age 18: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to reflect the level of systemic chronic inflammation. MDD risk scores calculated at age 12 were positively associated with levels of suPAR (but not CRP or IL-6) at age 18 after adjusting for key covariates (b = 1.70, 95% CI = 0.46 – 2.95, p = 0.007). Adolescents at high risk of MDD (risk scores ≥ 90th centile) had significantly higher mean levels of suPAR six years later than adolescents who had been identified as low risk (risk scores ≤ 10th centile) (b = 0.41, 95% CI = 0.18 – 0.64, p < 0.001). Findings support the notion that childhood psychosocial risk for MDD leads to increased levels of low-grade inflammation. If replicated in studies with repeated assessments of inflammation biomarkers throughout childhood and adolescence, these findings would support targeted interventions to reduce inflammation, as measured by suPAR, for adolescents at high risk of MDD to potentially prevent development of depression and physical health problems related to chronic inflammation.

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