title: Unipolar depression and hippocampal volume: impact of DNA sequence variants of the glucocorticoid receptor gene.
abstract: Glucocorticoid receptor (GR) plays a major role in regulation of the hypothalamic-pituitary-adrenocortical (HPA) system; HPA dysregulation represents the most consistent biological pattern of depression. Multiple functional polymorphisms are known for the GR gene, which might influence the development of unipolar depression. Previous studies reported associations to some variants in this gene but not consistently so. We investigated seven genetic polymorphisms in the GR gene (NR3C1) located in the putative promoter, exon 2 and intron 2 region. Study populations were 322 German inpatients with recurrent unipolar depression, and 298 German controls recruited from the general population. The relationships between intermediate phenotypes (hippocampal and amygdala volumes) and NR3C1 DNA sequence variants were additionally explored in a subpopulation of patients. We found association between the diagnosis of depression and DNA sequence variants in intron 2 as well as in the 5' region of the NR3C1 gene but not for the previously studied exon 2 and putative promoter variants (global test after control of multiple testing, P = 0.02). In patients, diagnosis-related alleles were also associated to hippocampal volume reduction and amygdala volume variation. Unipolar depression is associated with DNA variants of the NR3C1 gene in our population. Neurobiological underpinnings of depression as volumetric reductions of the hippocampus may also be mediated by variants in this gene.
authors.affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany. astrid.zobel@ukb.uni-bonn.de
authors.forename: Astrid
authors.initials: A
authors.lastname: Zobel
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Olrik
authors.initials: O
authors.lastname: von Widdern
authors.forename: Anna
authors.initials: A
authors.lastname: Schuhmacher
authors.forename: Susanne
authors.initials: S
authors.lastname: Höfels
authors.forename: Martin
authors.initials: M
authors.lastname: Metten
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Lukas
authors.initials: L
authors.lastname: Scheef
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Block
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Hans H
authors.initials: HH
authors.lastname: Schild
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Sibylle G
authors.initials: SG
authors.lastname: Schwab
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000679:Amygdala / Q000473:pathology; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5; D004252:DNA Mutational Analysis; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics; D011859:Radiography; D011965:Receptors, Glucocorticoid / Q000235:genetics*
chemical_list: D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid