Migraine comorbidities : Associations with psychiatric and gastrointestinal disorders

Sammanfattning: Migraine is a prevalent neurological disorder with a complex pathophysiology. One factor that potentially complicates migraine treatment is comorbidity between migraine and other disorders, including psychiatric and gastrointestinal disorders.In Paper I, associations between migraine and symptoms of peripartum depression and anxiety were explored, including assessments in early/mid-pregnancy, late pregnancy and in the postpartum period. A history of migraine was found to be associated with symptoms of anxiety in early/mid-pregnancy and with symptoms of both depression and anxiety in late pregnancy, after adjusting for confounding factors.In Paper II, cross-sectional associations between migraine and several gastrointestinal disorders were investigated. Migraine was associated with irritable bowel syndrome and peptic ulcers in the fully adjusted model. While Helicobacter pylori infection and coeliac disease were associated with migraine in unadjusted analyses, there were no significant associations between migraine and Crohn’s disease or ulcerative colitis.In Paper III, associations between use of proton-pump inhibitors (PPIs) and migraine were investigated. As PPIs are largely metabolised by the enzyme CYP2C19, participants were categorised according to their CYP2C19 phenotypes. PPI use was associated with a greater prevalence and incidence of migraine in both cross-sectional and prospective analyses. Metaboliser phenotype affected some of the outcomes in stratified analyses.In Paper IV, summary statistics from genome-wide association studies were used to assess genetic correlations and causal associations between migraine and both inflammatory bowel disese (IBD) and coeliac disease. There was no evidence of genetic correlations between any of the disorders, and there was no indication of causality. Nominally significant results were obtained in subtype analyses. Together, these results indicate that migraine is associated with symptoms of depression and anxiety in the peripartum period as well as with irritable bowel syndrom, peptic ulcers and use of PPIs in adults, thus adding to the literature on comorbidity in migraine. The previously observed associations between migraine and both IBD and coeliac disease were not corroborated in these studies, and the basis of these associations, if present, does not appear to be accounted for by shared genetics.