Background A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers. Method In a prospective occupational cohort study of British white-collar civil servants (the Whitehall II study), serum C-reactive protein, interleukin-6 and cognitive symptoms of depression were measured at baseline in 1991–1993 and at follow-up in 2002–2004, an average follow-up of 11.8 years. Symptoms of depression were measured with four items describing cognitive symptoms of depression from the General Health Questionnaire. The number of participants varied between 3339 and 3070 (mean age 50 years, 30% women) depending on the analysis. Results Baseline C-reactive protein (β=0.046, p =0.004) and interleukin-6 (β=0.046, p =0.005) predicted cognitive symptoms of depression at follow-up, while baseline symptoms of depression did not predict inflammatory markers at follow-up. After full adjustment for sociodemographic, behavioural and biological risk factors, health conditions, medication use and baseline cognitive systems of depression, baseline C-reactive protein (β=0.038, p =0.036) and interleukin-6 (β=0.041, p =0.018) remained predictive of cognitive symptoms of depression at follow-up. Conclusions These findings suggest that inflammation precedes depression at least with regard to the cognitive symptoms of depression.

Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study