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Unipolar depression and hippocampal volume: Impact of DNA sequence variants of the glucocorticoid receptor gene
Author(s) -
Zobel Astrid,
Jessen Frank,
von Widdern Olrik,
Schuhmacher Anna,
Höfels Susanne,
Metten Martin,
Rietschel Marcella,
Scheef Lukas,
Block Wolfgang,
Becker Tim,
Schild Hans H.,
Maier Wolfgang,
Schwab Sibylle G.
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30709
Subject(s) - glucocorticoid receptor , genetics , gene , exon , biology , intron , allele , population , medicine , environmental health
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. © 2008 Wiley‐Liss, Inc.