Anxiety disorders in childhood are associated with youth IL-6 levels: A mediation study including metabolic stress and childhood traumatic events.

Anxiety disorders (ADs) are chronic conditions that often have their onset in childhood and adolescence. Inflammation and oxidative stress markers have been associated with the vulnerability to ADs, however it is not known if ADs in childhood can influence these biomarkers levels longitudinally. This study aims to investigate a possible association between ADs and serum levels of IL-10, IL-6, IL-1ß, TNF-α, BDNF, and protein carbonyl content, assessed after 5 years of follow-up. Moreover, we studied possible mediators for these associations, including physical activity, metabolic markers and childhood trauma. From 240 individuals evaluated at baseline, 73 were re-evaluated in the follow-up. Psychiatric diagnoses were assessed with the K-SADS or the MINI and child trauma questionnaire (CTQ) to evaluate presence of trauma. We searched serum levels of IL-10, IL-6, IL-1ß and TNF-α (flow cytometry), BDNF (sandwich-ELISA) and carbonyl content in proteins (PCC method). We found a significant direct association between ADs at baseline and log IL-6 (B = 0.34, S.E. = 0.11, p = 0.002) and between AD and log BDNF (B = -0.10, S.E. = 0.05, p = 0.033) five years later. Searching for possible mediators of these association, we found that levels of HDL-cholesterol (ΔB = -0.148) partially mediated the association between ADs and IL-6. No significant mediators were found in the association between ADs and BDNF. Moreover, this association is no longer significant after controlling for the presence of depression. Our results demonstrated that previous AD diagnosis was associated with higher levels of IL-6 in the follow-up evaluation, suggesting that the presence of anxiety in childhood could influence altered inflammatory markers.