Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
OBJECTIVE
To assess the magnitude and direction of associations of depression with C-reactive protein (CRP), interleukin (IL)-1, and IL-6 in community and clinical samples.


METHODS
Systematic review of articles published between January 1967 and January 2008 in the PubMed and PsycINFO electronic databases was performed. Effect sizes were calculated as stat d and meta-analyzed, using random-effects models.


RESULTS
Each inflammatory marker was positively associated with depression; CRP, d = 0.15 (95% CI = 0.10, 0.21), p < .001; IL-6, d = 0.25 (95% CI = 0.18, 0.31), p < .001; IL-1, d = 0.35 (95% CI = 0.03, 0.67), p = .03; IL-1ra, d = 0.25 (95% CI = 0.04, 0.46), p = .02. Associations were strongest in clinically depressed patient samples--but were also significant in community-based samples--and when clinical interviews were used. Studies adjusting for body mass index (BMI) had smaller associations, albeit significant. Relationships were inconsistent with respect to age, medication, and sex. Depression was related to CRP and IL-6 among patients with cardiac disease or cancer.


CONCLUSIONS
Depression and CRP, IL-1, and IL-6 are positively associated in clinical and community samples and BMI is implicated as a mediating/moderating factor. Continuity in clinic- and community-based samples suggests there is a dose-response relationship between depression and these inflammatory markers, lending strength to the contention that the cardiac (or cancer) risk conferred by depression is not exclusive to patient populations. Available evidence is consistent with three causal pathways: depression to inflammation, inflammation to depression, and bidirectional relationships.
Howren
M Bryant
MB
Department of Psychology, The University of Iowa, 11 Seashore Hall East, Iowa City, IA 52242, USA.
Lamkin
Donald M
DM
Suls
Jerry
J
D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis*; D015984:Causality; D015897:Comorbidity; D003863:Depression / Q000097:blood* / Q000453:epidemiology; D003866:Depressive Disorder / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000453:epidemiology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000453:epidemiology; D007375:Interleukin-1 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology; D012737:Sex Factors
C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D002097:C-Reactive Protein