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

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

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.

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.