Association between stressful life events and autoimmune diseases: A systematic review and meta-analysis of retrospective case-control studies

Background: Evidence of a relationship between stressful life events and the onset of autoimmune diseases is not univocal and there are no meta-analyses in the literature on the question. Aim: To look for differences in the number and type of stressful life events in the premorbid period between patients with autoimmune diseases and healthy subjects. Method: Review of the literature in PubMed and Scopus (January 1963-May 2015). Inclusion criteria: We included retrospective case-control studies that compared patients diagnosed with autoimmune disorders and controls regarding the incidence of stressful events occurring before diagnosis, and investigated said events with validated questionnaires. Effect-size indexes: By random effect meta-analysis, two independent researchers calculated effect-size indexes as the difference between the means of the clinical groups and the control group in relation to the combined standard deviation. Results: The database searches produced 2490 articles, 14 of which were selected (3201 patients). Analysis showed a moderate but significant mean effect-size index [d = 0.63, p < 0.01], suggesting that autoimmune disorders are effectively associated with major stressful events in the premorbid period. The relationship between stressful events and autoimmune disease was weaker in studies with a high proportion of female subjects [beta = 0.004, p < 0.01] and stronger in studies that considered a longer interval between stressors and onset of disease [beta = 0.16, p < 0.01]. Conclusions: The results of this meta-analysis suggest that stressors may play an important role in the etiopathogenesis of autoimmune disorders. Only prospective studies can provide more certain inference about the causality of this relationship. (C) 2015 Elsevier B.V. All rights reserved.