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

Autoimmun Rev. 2016 Apr;15(4):325-34. doi: 10.1016/j.autrev.2015.12.005. Epub 2015 Dec 18.


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 [β=-0.004, p<0.01] and stronger in studies that considered a longer interval between stressors and onset of disease [β=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.

Keywords: Autoimmune disease; Meta-analysis; Stress; Stressful life events.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Autoimmune Diseases / immunology*
  • Case-Control Studies
  • Humans
  • Life Change Events*
  • Retrospective Studies
  • Surveys and Questionnaires