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Unipolar depression and hippocampal volume: impact of DNA sequence variants of the glucocorticoid receptor gene

Journal Article


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.

UOW Authors


  •   Zobel, Astrid W. (external author)
  •   Jessen, Frank (external author)
  •   von Widdern, Olrik (external author)
  •   Schuhmacher, Anna (external author)
  •   Hofeis, Susanne (external author)
  •   Metten, Martin (external author)
  •   Rietschel, Marcella (external author)
  •   Scheef, Lukas (external author)
  •   Block, Wolfgang (external author)
  •   Becker, Tim (external author)
  •   Schild, Hans H. (external author)
  •   Maier, Wolfgang (external author)
  •   Schwab, Sibylle

Publication Date


  • 2008

Citation


  • Zobel, A., Jessen, F., von Widdern, O., Schuhmacher, A., Hofeis, S., Metten, M., Rietschel, M., Scheef, L., Block, W., Becker, T., Schild, H. H., Maier, W. & Schwab, S. G. (2008). Unipolar depression and hippocampal volume: impact of DNA sequence variants of the glucocorticoid receptor gene. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147 (6), 836-843.

Scopus Eid


  • 2-s2.0-51449124236

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/487

Number Of Pages


  • 7

Start Page


  • 836

End Page


  • 843

Volume


  • 147

Issue


  • 6

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.

UOW Authors


  •   Zobel, Astrid W. (external author)
  •   Jessen, Frank (external author)
  •   von Widdern, Olrik (external author)
  •   Schuhmacher, Anna (external author)
  •   Hofeis, Susanne (external author)
  •   Metten, Martin (external author)
  •   Rietschel, Marcella (external author)
  •   Scheef, Lukas (external author)
  •   Block, Wolfgang (external author)
  •   Becker, Tim (external author)
  •   Schild, Hans H. (external author)
  •   Maier, Wolfgang (external author)
  •   Schwab, Sibylle

Publication Date


  • 2008

Citation


  • Zobel, A., Jessen, F., von Widdern, O., Schuhmacher, A., Hofeis, S., Metten, M., Rietschel, M., Scheef, L., Block, W., Becker, T., Schild, H. H., Maier, W. & Schwab, S. G. (2008). Unipolar depression and hippocampal volume: impact of DNA sequence variants of the glucocorticoid receptor gene. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147 (6), 836-843.

Scopus Eid


  • 2-s2.0-51449124236

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/487

Number Of Pages


  • 7

Start Page


  • 836

End Page


  • 843

Volume


  • 147

Issue


  • 6