Associations between IL-6 and trajectories of depressive symptoms across the life course: Evidence from ALSPAC and UK Biobank cohorts

Background
Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

Methods
We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10-28 years; N=4,835) and UK Biobank (39-86 years; N=39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points=11) and the Patient Health Questionnaire-2 in UK Biobank (max time points=8).

Results
Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

Conclusions
These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.