title: Multiple sclerosis and psychiatric disorders: comorbidity and sibling risk in a nationwide Swedish cohort.
abstract: BACKGROUND
  Psychiatric disorders are known to be prevalent in multiple sclerosis (MS).
  
  
  OBJECTIVE
  The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association.
  
  
  METHODS
  We identified ICD-diagnosed patients with MS (n = 16,467), bipolar disorder (n = 30,761), schizophrenia (n = 22,781) and depression (n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison.
  
  
  RESULTS
  The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6-2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant.
  
  
  CONCLUSIONS
  We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden viktoria.johansson@ki.se.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Johansson
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lundholm
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Masterman
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hultman
mesh_terms: D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D003866:Depressive Disorder / Q000453:epidemiology; D003865:Major Depressive Disorder / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology*; D015995:Prevalence; D012559:Schizophrenia / Q000453:epidemiology*; D035781:Siblings; D013548:Sweden / Q000453:epidemiology
keywords: Multiple sclerosis; bipolar disorder; cohort study; depression; genetic liability; schizophrenia