Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life

By G. Khandaker, R. Pearson, S. Zammit, G. Lewis, Peter B. Jones. JAMA psychiatry, 2014

802 citations recorded by the source corpus.

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.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Cardiology and Cardiovascular Medicine

View Paper: https://www.semanticscholar.org/paper/55097618fe2b604979de5f5afd0ee5918610c6ad

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M. Kivimaki

Citations in the corpus

Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder (2015, background): “, 2012), predictive associations of IL-6 and CRP with the future development of mood disorders (Gimeno et al., 2009; Khandaker et al., 2014; Kivimaki et al., 2014; Virtanen et al., 2015; Wium-Andersen et al., 2013), evidence of dose–response relationships (Kivimaki et al.”
Inflammation: depression fans the flames and feasts on the heat. (2015, background): “Childrenwithhigher IL-6 levels at age 9weremore likely to be depressed at age 18 compared with those with low IL-6 levels; importantly, IL-6 was measured prior to depression onset, thus suggesting that high IL-6 is indeed a risk factor (12).”
Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels (2019, background): “…of CRP and IL-6 at baseline are associated with an increased risk of depression in subsequent follow-ups (Gimeno et al., 2009; Wium-Andersen et al., 2013; Khandaker et al., 2014; Zalli et al., 2016), suggesting that inflammation could be a cause rather than simply a consequence of the illness.”
Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness (2016, background): “cytokines in childhood and are also associated with the high risk of mental illness in adulthood (Khandaker et al. 2014; Danese et al. 2008).”