Early-life inflammatory markers and subsequent episodes of depression and psychotic experiences in the ALSPAC birth cohort

Abstract

Background Inflammation is implicated in depression and psychosis, including association of childhood inflammatory markers on the subsequent risk of developing symptoms. However, it is unknown whether early-life inflammatory markers are associated with the number of depressive and psychotic symptoms from childhood to adulthood. Methods Using the prospective Avon Longitudinal Study of Children and Parents birth cohort (N=up-to 6,401), we have examined longitudinal associations of early-life inflammation [exposures: interleukin-6 (IL-6), C-reactive protein (CRP) levels at age 9y; IL-6 and CRP DNA-methylation (DNAm) scores at birth and age 7y; and IL-6 and CRP polygenic risk scores (PRSs)] with the number of depressive episodes and psychotic experiences (PEs) between ages 10-28 years. Psychiatric outcomes were assessed using the Short Mood and Feelings Questionnaire and Psychotic Like Symptoms Questionnaires, respectively. Exposure-outcome associations were tested using negative binomial models, which were adjusted for metabolic and sociodemographic factors. Results Serum IL-6 levels at age 9y were associated with the total number of depressive episodes between 10-28y (n=4,262; β=0.086; 95%CI:0.036-0.137; pFDR=0.009). CRP DNAm score at birth was associated with total number of PEs, size but this association did not survive correction for multiple testing (n=822; β=0.204; 95%CI:0.024-0.388; p uncorrected=0.027; pFDR=0.252). Other immune measures were not associated with depression or PEs. Conclusions Early-life inflammatory markers are associated with the burden of depressive episodes and of PEs subsequently from childhood to adulthood. These findings support a potential role of early-life inflammation in the aetiology of depression and psychosis and highlight inflammation as a potential target for treatment and prevention.