title: Glucocorticoid receptor polymorphism is associated with major depression and predominance of depression in the course of bipolar disorder.
abstract: BACKGROUND
  A strong association has been found between dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and depression and bipolar disorder. Glucocorticoid receptor is one of the involved receptors and its gene has been recognized as a candidate gene for major depressive disorder and bipolar disorder. Therefore, we investigated if polymorphism of the glucocorticoid receptor gene (NR3C1), involved in the regulation of HPA axis, may alter susceptibility as well as the course of major depressive disorder and bipolar disorder.
  
  
  METHODS
  In the study we included 514 patients with bipolar disorder and 193 patients with major depressive disorder. Consensus diagnosis by at least two psychiatrists was made, according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria, using SCID (Structured Clinical Interview for DSM Disorders). Control group consisted of 732 healthy subjects. Genotyping for eight NR3C1 polymorphisms was done with use of TaqMan SNP (single nucleotide polymorphism) Genotyping Assays. Linkage disequilibrium analysis was done in Haploview.
  
  
  RESULTS
  We have found three polymorphisms (rs6198, rs6191 and rs33388) to be associated with major depressive disorder (MDD) and the same polymorphisms were associated with the predominance of depressive symptoms in the course of bipolar disorder. In linkage disequilibrium analysis we observed two haplotype blocks, however, none of those shows involvement in susceptibility to MDD or bipolar disorder.
  
  
  CONCLUSIONS
  The main limitation of this study is relatively small sample size of MDD patients group.
  
  
  CONCLUSIONS
  Polymorphisms of NR3C1 gene analyzed in this study may modify susceptibility to major depressive disorder and seem to influence the course of bipolar disorder.
authors.affiliation: Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poland. alszczep@amp.edu.pl
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczepankiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Leszczyńska-Rodziewicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Pawlak
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rajewska-Rager
authors.forename: Monika
authors.initials: M
authors.lastname: Dmitrzak-Weglarz
authors.forename: Monika
authors.initials: M
authors.lastname: Wilkosc
authors.forename: Maria
authors.initials: M
authors.lastname: Skibinska
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D003863:Depression / Q000235:genetics; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007030:Hypothalamo-Hypophyseal System; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011965:Receptors, Glucocorticoid / Q000235:genetics*
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid