title: Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression.
abstract: BACKGROUND
  Many studies have explored the association between soluble interleukin-2 receptor (sIL-2R), cytokines and major depressive disorder (MDD). However, the results of these studies were not consistent. The aim of our study is to compare the levels of sIL-2R and cytokines in the blood between MDD patients and controls by a meta-analysis and to identify moderators accounting for potential heterogeneity in the levels of sIL-2R and cytokines in MDD patients versus controls by meta-regression analyses.
  
  
  METHODS
  A comprehensive literature search was performed to identify studies comparing the levels of sIL-2R and cytokines between MDD patients and controls. We pooled the effect sizes for standardized mean differences (SMD) of the levels of sIL-2R and cytokines. We also performed meta-regression and sensitivity analyses to investigate the roles of age, gender, sample type, ethnic origin and selected studies' quality in explaining potential heterogeneity and differences in results respectively.
  
  
  RESULTS
  Twenty-nine studies were selected for this analysis. The levels of sIL-2R, TNF-α and IL-6 in MDD patients were significantly higher than those of healthy controls (SMD=0.555, p<0.001, SMD=0.567, p=0.010; SMD=0.680, p<0.001). Mean age of all subjects was a significant moderator to explain the high heterogeneity of IL-6. Sensitivity analysis found that European but not non-European subjects have higher levels difference of sIL-2R, TNF-α and IL-1β between MDD patients and controls.
  
  
  CONCLUSIONS
  The severity of MDD was not considered.
  
  
  CONCLUSIONS
  The blood levels of sIL-2R, TNF-α and IL-6 were significantly higher in MDD patients than controls. Age, samples source and ethnic origins may play a potential role in heterogeneity.
authors.affiliation: Department of Psychological Medicine, University Medicine Cluster, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Roger Chun-Man
authors.initials: RC
authors.lastname: Ho
authors.forename: Anselm
authors.initials: A
authors.lastname: Mak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D016207:Cytokines / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055815:Young Adult
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha