CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies

Journal article

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 = 0.08,12=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). Limitations: 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. © 2013 Elsevier B.V. All rights reserved.

Authors: Valkanova, V; Ebmeier, K; Allan, C

• Journal: Journal of Affective Disorders
• Volume: 150
• Issue: 3
• Pages: 736-744
• Publication date: 2013-09-25
• DOI: 10.1016/j.jad.2013.06.004
• EISSN: 1573-2517
• ISSN: 0165-0327