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Original Investigation |

Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life:  A Population-Based Longitudinal Study

Golam M. Khandaker, PhD1,2,3,4,5; Rebecca M. Pearson, PhD5; Stanley Zammit, PhD5,6; Glyn Lewis, PhD5,7; Peter B. Jones, PhD1,2,3,4
[+] Author Affiliations
1Department of Psychiatry, University of Cambridge, Cambridge, England
2National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, England
3Collaboration for Leadership in Applied Health Research and Care, East of England, Cambridge, England
4Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, England
5Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, Bristol, England
6Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales
7Division of Psychiatry, University College London, London, England
JAMA Psychiatry. 2014;71(10):1121-1128. doi:10.1001/jamapsychiatry.2014.1332.
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Importance  Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear.

Objective  To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis.

Design, Setting, and Participants  The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments.

Measurement of Exposure  Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years.

Main Outcomes and Measures  Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule–Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview.

Results  After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner.

Conclusions and Relevance  Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.

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Figure.
Depression and Psychotic Experiences at Age 18 Years in the Avon Longitudinal Study of Parents and Children

Samples of depression (A) and psychotic experiences (B) were divided by tertiles of interleukin 6 (IL-6) in participants at age 9 years. Cutoff values for the top and bottom thirds of the distribution of IL-6 values in the total sample (cases and noncases combined) were 1.08 and 0.57 pg/mL, respectively.

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