Elevated Interleukin-6 During Childhood May be Marker for Psychosis or Depression During Adulthood

While cross-sectional studies have reported elevated concentrations of inflammatory markers in psychosis and depression, there are questions regarding temporality and specificity of association, crucial for understanding the potential role of inflammation.

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).

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