Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality: a mendelian randomization study.
BACKGROUND
Elevated levels of plasma C-reactive protein (CRP) have been associated with many diseases including depression, but it remains unclear whether this association is causal. We tested the hypothesis that CRP is causally associated with depression, and compared these results to those for cancer, ischemic heart disease, chronic obstructive pulmonary disease, and all-cause mortality.


METHODS
We performed prospective and instrumental variable analyses using plasma CRP levels and four CRP genotypes on 78,809 randomly selected 20- to 100-year-old men and women from the Danish general population. End points included hospitalization or death with depression and somatic diseases, prescription antidepressant medication use, and all-cause mortality.


RESULTS
A doubling in plasma CRP yielded an observed odds ratio (OR) of 1.28 (95% confidence interval [CI]: 1.23-1.33) for hospitalization or death with depression, whereas for genetically elevated CRP, the causal OR was .79 (95% CI: .51-1.22; observed vs. causal estimate, p = .03). For prescription antidepressant medication use, corresponding ORs were 1.12 (1.11-1.15) and .98 (.83-1.15; p = .08). These results were similar to those for risk of cancer (p = .002), ischemic heart disease (p = 4 × 10(-99)), chronic obstructive pulmonary disease (p = 6 × 10(-86)), and all-cause mortality (p = .001) examined in the same individuals.


CONCLUSIONS
Elevated CRP was associated with increased risk of depression in individuals in the general population, but genetically elevated CRP was not. This indicates that CRP per se is not a causal risk factor for depression.
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Marie Kim
MK
Wium-Andersen
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
David Dynnes
DD
Orsted
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.. Electronic address: Boerge.Nordestgaard@regionh.dk.
Børge Grønne
BG
Nordestgaard
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000097:blood* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000401:mortality; D009369:Neoplasms / Q000097:blood / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011660:Pulmonary Heart Disease / Q000097:blood / Q000401:mortality; D013315:Stress, Psychological / Q000097:blood; D055815:Young Adult
D002097:C-Reactive Protein
All-cause mortality; CRP; depression; genetic variants; inflammation; mendelian randomization; somatic disease