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Childhood Inflammatory Markers and Intelligence as Predictors of Subsequent Persistent Depressive Symptoms: A Longitudinal Cohort Study

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Khandaker, GM 
Zammit, S 
Glyn, L 


Background: To identify developmental sub-groups of depressive symptoms during the second decade of life, a critical period of brain development, using data from a prospective birth cohort. To test whether childhood intelligence and inflammatory markers are associated with subsequent persistent depressive symptoms. Methods: IQ, a proxy for neurodevelopment, was measured at age 8 years. Interleukin 6 (IL-6) and C-reactive protein (CRP), typical inflammatory markers, were measured at age 9 years. Depressive symptoms were measured six times between 10 and 19 years using the short mood and feelings questionnaire (SMFQ), which were coded as binary variable and then used in latent class analysis to identify developmental sub-groups of depressive symptoms. Results: Longitudinal SMFQ data from 9156 participants yielded three distinct population sub-groups of depressive symptoms: no symptoms (81.2%); adolescent-onset symptoms (13.2%); persistent symptoms (5.6%). Lower IQ and higher IL-6 levels in childhood were independently associated with subsequent persistent depressive symptoms in a linear, dose-response fashion, but not with adolescent-onset symptoms. Compared with the group with no symptoms the adjusted odds ratio for persistent depressive symptoms per SD increase in IQ was 0.80 (95% CI, 0.68-0.95); that for IL-6 was 1.20 (95% CI, 1.03-1.39). Evidence for an association with IL-6 remained after controlling for initial severity of depressive symptoms at 10 years. There was no evidence that IL-6 moderated or mediated the IQ-persistent depressive symptom relationship. Conclusions: The results indicate potentially important roles for two distinct biological processes, neurodevelopment and inflammation, in the aetiology of persistent depressive symptoms in young people.



CRP, IL-6, IQ, depression, depressive symptoms, immunopsychiatry, inflammation, intelligence, latent class analysis, longitudinal study, neurodevelopment, Adolescent, Biomarkers, C-Reactive Protein, Child, Depression, England, Female, Humans, Inflammation, Intelligence, Intelligence Tests, Interleukin-6, Logistic Models, Longitudinal Studies, Male, Predictive Value of Tests, Sex Characteristics, Young Adult

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Psychological Medicine

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Cambridge University Press
Academy of Medical Sciences (unknown)
Wellcome Trust (201486/Z/16/Z)
National Institute for Health Research (NIHR) (via Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
Wellcome Trust (088869/Z/09/Z)
Wellcome Trust (095844/Z/11/Z)
National Institute for Health and Care Research (RP-PG-0606-1335)
Dr Khandaker is supported by an Intermediate Clinical Fellowship from the Wellcome Trust (201486/Z/16/Z) and a Clinical Lecturer Starter Grant from the Academy of Medical Sciences, UK (grant no. 80354). Professor Jones acknowledges grant support from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z) and NIHR (RP-PG-0606-1335, Cambridge Biomedical Research Centre and CLAHRC East of England). Dr Stochl is supported by the UK Medical Research Council (MRC award ref: MR/K006665/1) and by the NIHR CLAHRC East of England.