Bidirectional Associations Between Inflammatory Biomarkers and Depressive Symptoms in Adolescents: Potential Causal Relationships

There are inconsistent findings in the literature about the directionality and magnitude of the association between inflammation and depressive symptoms. This analysis separates predictors into between-persons and within-person components to gain greater clarity about this relationship. Blood samples were collected and depressive symptoms assessed in 140 adolescents (54% female, 59% Black; mean age = 16.1 years) with at least three blood draws and a total of 394 follow-up observations. Multilevel modeling indicated that the within-persons effect of tumor necrosis factor alpha predicted change in total depressive symptoms, which suggests a potential causal relationship. There were no significant within-persons effects of total depressive symptoms on change in biomarkers. Exploratory analyses examined associations between inflammatory biomarkers and subsets of depressive symptoms. These findings inform modeling decisions that may explain inconsistencies in the extant literature as well as suggest potential causal relationships between certain proteins with significant within-persons effects on depressive symptoms and vice-versa.