title: CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies.
abstract: BACKGROUND
  Inflammatory markers are raised in cross-sectional studies of depressed patients and may represent an important mediating factor for behaviour, neural plasticity and brain structure.
  
  
  METHODS
  We undertook a systematic review of longitudinal studies, investigating whether raised inflammatory markers indicate an increased risk of subsequent depressive symptoms. We searched three databases (1970-2012) for longitudinal studies with repeat data on CRP or IL-6 levels and subsequent depressive symptoms. We calculated effect sizes using a mixed-effects model, with separate meta-analyses for inflammatory markers and age groups.
  
  
  RESULTS
  We identified eight papers for CRP (14,832 participants) and three for IL-6 (3695 participants). There was a significant association between increased CRP and depressive symptoms (weighted-mean effect size 'unadjusted r'=0.069, p<0.0005; 'adjusted r'=0.046, p<0.0005), with moderate heterogeneity between studies (Q=11.21, p=0.08, I(2)=46.5). For IL-6 the weighted-mean effect size was smaller ('unadjusted r'=0.045, p-value=0.007; 'adjusted r'=0.097, p-value=0.06).
  
  
  CONCLUSIONS
  The meta-analysis was based on a relatively small number of studies (particularly for IL-6) and only two inflammatory markers. There was moderate heterogeneity between studies and some evidence of publication bias.
  
  
  CONCLUSIONS
  Raised inflammatory markers have a small but significant association with the subsequent development of depressive symptoms. This is a robust effect which remains significant after adjustment for age and a wide range of factors associated with risk for depression. Our results support the hypothesis that there is a causal pathway from inflammation to depression.
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, United Kingdom.
authors.forename: Vyara
authors.initials: V
authors.lastname: Valkanova
authors.forename: Klaus P
authors.initials: KP
authors.lastname: Ebmeier
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Allan
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: CRP; Depressive; IL-6; Inflammation; Longitudinal; Meta-analysis