title: Inflammatory markers and the pathogenesis of pediatric depression and suicide: a systematic review of the literature.
abstract: OBJECTIVE
  To evaluate the relationship and identify support for pathways linking inflammatory processes with depression and suicide in children and adolescents.
  
  
  METHODS
  We designed and implemented comprehensive literature searches in MEDLINE, PsycINFO, and EMBASE. We searched the databases with database-specific controlled vocabulary in conjunction with keywords (eg, inflammation, interleukin, cytokine, C-reactive protein, depression, suicide) in various combinations for reports published in English through May 2013.
  
  
  METHODS
  The searches identified a total of 1,543 citations, of which 55 were selected for further review and ultimately 27 were identified for inclusion. Studies were selected using 2 criteria. The first criterion required that studies include a biological measure of inflammatory markers in childhood or adolescence. The second criterion required that the studies include a measure of depression or suicide in childhood or adolescence. Articles selected for the review were based on the use of standardized experimental procedures and validated assessment measures.
  
  
  METHODS
  All articles were assessed by 2 authors, which ensured that the inclusion criteria were met. Studies were reviewed for association of inflammatory markers with depression and/or suicide. Extracted data included authors, year of publication, study design, population characteristics, inflammatory markers, and depression/suicide measures. Significant and nonsignificant findings were tabulated.
  
  
  RESULTS
  The majority of studies were on depression; 2 studies were on suicide, and 7 studies were on inflammatory medical conditions. Most of the participants were adolescents. Interleukin (IL)-1α, IL-1β, IL-1 receptor antagonist, IL-2, soluble IL-2 receptors, IL-4, IL-6, IL-10, interferon-γ, tumor necrosis factor-α, C-reactive protein, erythrocyte sedimentation rate, and inflammatory cells were assayed across the studies. There was extensive variation in depression measures. Five of the 9 cross-sectional and 3 of the 7 longitudinal studies on depression found a positive association between inflammation and depression. In 3 studies evaluating depression and early adversity, inflammation was more significantly related to adversity than depression was. Results from studies of medical conditions involving inflammation and depression were mixed.
  
  
  CONCLUSIONS
  The extant literature provides sufficient data to support a link between inflammatory processes and pediatric depression. However, the directionality of the associations and pathways between the 2 conditions remains to be elucidated. At present, there is insufficient evidence to support the relationship between inflammation and suicidality in youth. Studies on inflammatory medical conditions are warranted in order to understand biological pathways linking inflammation and depression.
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Eva M
authors.initials: EM
authors.lastname: Szigethy
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Melhem
authors.forename: Ester M
authors.initials: EM
authors.lastname: Saghafi
authors.forename: David A
authors.initials: DA
authors.lastname: Brent
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D002648:Child; D016207:Cytokines; D003863:Depression / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D013405:Suicide
chemical_list: D015415:Biomarkers; D016207:Cytokines