The association between adverse childhood experiences and inflammation in patients with major depressive disorder: A systematic review.

Abstract Background Replicated evidence has documented elevated levels of pro-inflammatory cytokines in populations with major depressive disorder (MDD). However, childhood trauma, a risk factor for MDD, has been separately shown to also impact inflammatory systems; Its potential moderating effect on inflammation in MDD has been less frequently investigated. Methods We systematically searched the PubMed, Google Scholar, Scopus, Web of Science, and PsycINFO databases between database inception to June 19th, 2019 using the search string: (Childhood trauma or Adverse childhood experiences or childhood abuse or childhood rape or physical abuse or emotional abuse) AND (Inflammation or inflammatory cytokines or interleukin-6 or tumour necrosis factor-alpha or c-reactive protein) AND (Major Depressive Disorder or Depression). Results We identified nine articles that evaluated inflammatory biomarkers in MDD populations with adverse childhood experiences (ACE). Eight articles evaluated IL-6, three articles evaluated CRP, and five articles evaluated TNF-α. The strongest effects were observed for IL-6; six studies reported significantly elevated levels of IL-6 in MDD and ACE patients compared to healthy controls and/or MDD-only populations. Meanwhile, only three studies found TNF-α to be significantly elevated in the MDD and ACE cohort. In contrast, MDD-ACE populations did not exhibit significantly elevated CRP. Limitations The methodological heterogeneity amongst studies was very high. Conclusion The current review suggests that MDD and ACE subpopulations present elevated levels of IL-6 compared to MDD-only and healthy control populations. Therefore, research should consider whether elevated inflammation in MDD is just an epiphenomenon of previous ACE and whether MDD-ACE subgroups are more likely to respond to immune-inflammatory targeted intervention.