Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis.

BACKGROUND Depression is associated with elevated levels of the inflammation marker C-reactive protein (CRP); yet, the direction of this association remains unclear. This study tested bi-directional longitudinal associations between CRP and depression in a sample of adolescents and young adults. The study compared the effect of current depression with the effect of cumulative episodes of depression over time. METHODS Nine waves of data from the prospective population-based Great Smoky Mountains Study (n = 1420) were used, covering children in the community aged 9 to 16, 19, and 21 years old. Structured interviews were used to assess depressive symptoms, depression diagnosis, and cumulative depressive episodes. Bloodspots were collected at each observation and assayed for CRP levels. RESULTS CRP levels were not associated with later depression status. In contrast, all depression-related variables displayed evidence of association with later CRP levels. The associations with depressive symptoms and diagnostic status were attenuated after controlling for covariates, particularly body mass index, smoking, and medication use. The effect of cumulative depressive episodes, however, continued to be significant after accounting for a range of covariates. Body mass index, smoking behavior, and recent infections may mediate a portion of the effect of cumulative episodes on later CRP, but cumulative depressive episodes continued to predict CRP levels independently. CONCLUSIONS The occurrence of multiple depressive episodes exerted the greatest effect on later CRP levels. This suggests that risk for the diseases of middle and old age--cardiovascular and metabolic disease--may begin in childhood and depend, in part, on long-term emotional functioning.