Children with elevated interleukin-6 (IL-6) may be at increased risk for psychosis and depression during adulthood. These findings, from a birth cohort study, were published in Schizophrenia Research.

Pregnant women (N=14,541) were recruited for the Avon Longitudinal Study of Parents and Children (ALPAC) study in southwest England between 1991 and 1992. IL-6 and C-reactive protein (CRP) concentrations at age 9 were compared with psychosis (n=2224) and depression (n=2219) status at age 24.

At age 9, CRP and IL-6 concentrations were correlated (r, 0.45; P <.001).

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At age 24, 163 (7.3%) had psychotic experiences, 30 (1.3%) met the criteria for a psychotic disorder, and 214 (9.6%) had depressive episodes.

Increased IL-6 at age 9 was associated with increased risk for developing a psychotic disorder by age 24 (adjusted odds ratio [aOR], 1.56; 95% CI, 1.09-2.21; P =.014). Stratified by tertiles of IL-6 levels, those who had the highest levels were at increased risk for developing a psychotic disorder (aOR, 2.60; 95% CI, 1.04-6.53; P =.031) or depressive episode (aOR, 1.49; 95% CI, 1.02-2.18; P =.035).

Increased IL-6 was also associated with more negative symptoms of depression (adjusted b, 0.09; 95% CI, 1.09-2.21; P =.014). Stratified by depression type, IL-6 was more strongly (P =.014) associated with moderate/severe depressive episodes (aOR, 1.20; 95% CI, 1.05-1.36) than with mild depressive episodes (aOR, 1.12; 95% CI, 0.86-1.46).

There was no evidence that the associations between IL-6 and psychosis or depression were a common effect (P =.336), suggesting IL-6 levels may instead be a common risk factor.

This study was limited by not including diagnoses of schizophrenia in the model and the fact that having psychotic experiences does not mean that a psychotic disorder will develop with time.

The study authors concluded there was a dose-response association between IL-6 concentrations during childhood and psychosis or depression risk in adulthood. Additional studies are needed to determine whether IL-6 may be a useful clinical marker or whether it may be a possible interventional target.


Perry BI, Zammit S, Jones PB, Khandaker GM. Childhood inflammatory markers and risks for psychosis and depression at age 24: Examination of temporality and specificity of association in a population-based prospective birth cohort. Schizophr Res. 2021;230:69-76. doi:10.1016/j.schres.2021.02.008