title: The interaction of GSK3B and FXR1 genotypes may influence the mania and depression dimensions in mood disorders.
abstract: Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset.
  
  
  
  Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model.
  
  
  
  In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11% of mania variance and 5% of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A.
  
  
  
  Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample.
  
  
  
  We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec du Centre intégré universitaire en santé et services sociaux de la Capitale-Nationale, Québec, Canada; Département de médecine sociale et préventive, Université Laval, Québec, Canada. Electronic address: alexandre.bureau@msp.ulaval.ca.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bureau
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec du Centre intégré universitaire en santé et services sociaux de la Capitale-Nationale, Québec, Canada; Département de psychiatrie et neurosciences, Université Laval, Québec, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jean Martin
authors.initials: JM
authors.lastname: Beaulieu
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec du Centre intégré universitaire en santé et services sociaux de la Capitale-Nationale, Québec, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Paccalet
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec du Centre intégré universitaire en santé et services sociaux de la Capitale-Nationale, Québec, Canada; Département de psychiatrie et neurosciences, Université Laval, Québec, Canada.
authors.forename: Yvon C
authors.initials: YC
authors.lastname: Chagnon
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec du Centre intégré universitaire en santé et services sociaux de la Capitale-Nationale, Québec, Canada; Département de psychiatrie et neurosciences, Université Laval, Québec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Maziade
mesh_terms: D000328:Adult; D017668:Age of Onset; D001714:Bipolar Disorder / Q000523:psychology*; D003865:Major Depressive Disorder / Q000523:psychology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics*; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000523:psychology*; D011110:Polymorphism, Genetic; D015995:Prevalence; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C096916:FXR1 protein, human; D016601:RNA-Binding Proteins; D008094:Lithium; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Age of onset; Bipolar disorder; Epistasis, genetic; Fragile X autosomal homolog 1, Glycogen Synthase Kinase 3; Lithium