Inflammatory mediation of the relationship between early adversity and major depressive disorder: A systematic review

Early adverse experience is related to psychiatric illness that occurs decades later. The mechanisms underlying this phenomenon have not been fully identified. There is a translational and clinical literature linking early adversity with Major Depressive Disorder (MDD) and inflammation. We reviewed articles that examine whether inflammation mediates this relationship. Methods: Literature review of PUB MED, CINAHL and APA Psycinfo articles that explicitly examine inflammation as a mediator between early adversity and depression using ((((((((((adversity) OR (trauma)) OR (maltreatment)) OR (child abuse)) AND (inflammation)) OR (inflammatory cytokines)) OR (crp)) OR (il-6)) OR (tnf)) AND (mediates)) AND (depression))))))))) as key words. Results: 2842 articles were initially identified. 1338 non-human studies were excluded and 512 more were filtered out as reviews. The remaining 992 titles and, when necessary, abstracts and manuscripts were reviewed and 956 were removed as being of other non-related phenomena. Four additional studies were added by hand searching the references of remaining studies. Out of these 40, 15 explicitly examined inflammation as a mediator of the relationship between early adversity and later depression. Approximately half (8/15) showed evidence that inflammation mediated the relationship between early adversity and depression. Sensitivity analyses showed that studies taking place in clinical populations, in youth and those that used the Adverse Childhood Events Scale to measure adversity, and IL-6 and TNF-alpha (as opposed to CRP) to measure inflammation were most likely to show mediation. Conclusions: There is evidence to support the model of inflammation mediating the relationship between early adversity and depression. Certain measures in clinical populations appear more likely to support this model. Further study with more standardized, robust methods will help to answer this question more definitively and may elucidate a subtype of depression related to early adversity by alterations in immune function.