Childhood adversity as a risk factor for autoimmune disease: A systematic review and meta-analysis with implications for psychiatry

Abstract

Background: Autoimmune diseases are a heterogeneous category of disorders caused by an interaction between genetic and environmental factors which lead to a dysregulated immune response. Childhood adversity is an environmental risk factor with enduring effects on the immune system and may therefore be implicated in the aetiology of autoimmune disorders. This systematic review and meta-analysis sought to examine the association between childhood adversity and autoimmune disease in adulthood. Methods: Electronic databases (MEDLINE, PsycINFO, Embase, and Web of Science) were searched for peer-reviewed studies in English, examining rates of childhood adversity in adults with a diagnosis of any autoimmune disease. This study was registered with PROSPERO, CRD42023439745. Findings: The meta-analysis included 45 effect sizes from 27 studies (Ncases = 8,728, Ncontrol = 3,298,392). Results revealed a small effect (SMD = 0.30, 95 % CI [0.20–0.40], p < 0.001) of exposure to childhood adversity on autoimmune disease in adulthood. Heterogeneity was very high, and Egger's test and funnel plot inspection suggested that publication bias may be present. Rheumatoid arthritis (SMD = 0.48, 95 % CI [0.20–0.76], p < 0.001), psoriasis (SMD = 0.30, 95 % CI [0.17–0.43], p < 0.001), multiple sclerosis (SMD = 0.20, 95 % CI [0.01–0.38], p = 0.008), and inflammatory bowel disease (SMD = 0.31, 95 % CI [0.04–0.58], p = 0.024) were each associated with childhood adversity. Systemic lupus erythematosus was not (SMD = 0.17, 95 % CI [-0.06–0.41], p = 0.141). Twenty-one studies were assessed as being at high risk of bias. Interpretation: There is evidence of an association between a history of childhood adversity and autoimmune disorders. This exposure may contribute to the elevated comorbidity between autoimmune diseases and severe mental illnesses. Due to the heterogeneity of the evidence and the high risk of bias in numerous studies, however, results should be treated with caution. Possible mechanisms underlying the relationship and implications for treatment and prevention of autoimmune diseases are discussed.