BACKGROUND: No prospective studies have examined the role of C-reactive protein (CRP) in late-onset bipolar disorder.

AIMS: We tested the hypothesis that elevated levels of CRP are associated cross-sectionally and prospectively with late-onset bipolar disorder, and that such an association possibly is causal.

METHOD: We performed cross-sectional and prospective analyses with a median follow-up time of 5.9 years (interquartile range: 4.4-7.6) in 78 809 individuals from the general population, and used genetic variants influencing CRP levels to perform a Mendelian randomisation study.

RESULTS: Elevated levels of CRP were associated both cross-sectionally and prospectively with late-onset bipolar disorder. When CRP was on a continuous scale, a doubling in CRP yielded an observational odds ratio for late-onset bipolar disorder of 1.28 (1.08-1.52) with a corresponding causal odds ratio of 4.66 (0.89-24.3).

CONCLUSION: Elevated CRP is associated with increased risk of late-onset bipolar disorder in the general population which was supported by the genetic analysis.