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Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum

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Engineer, Neelam, Darwin, Lucy, Nishigandh, Deole, Kandala, Ngianga-Bakwin, Smith, Steve C. and Grammatopoulos, Dimitris (2013) Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum. Journal of Psychiatric Research, Volume 47 (Number 9). pp. 1166-1173. doi:10.1016/j.jpsychires.2013.05.003

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Official URL: http://dx.doi.org/10.1016/j.jpsychires.2013.05.003

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Abstract

Women with postnatal depression (PND) appear to have abnormal hypothalamic pituitary adrenal (HPA) axis responses to stress, which might involve a genetic variability component. We investigated association of genetic variants in the glucocorticoid receptor (GR, NR3C1) and corticotropin releasing hormone receptor 1 (CRHR1) genes with increased risk for PND. Two hundred pregnant women were recruited prospectively and PND risk was assessed by the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and again 2-8 weeks post-natally (CW-GAPND study). The BclI and ER22/23EK single nucleotide polymorphisms (SNPs) of the GR and the haplotype-tagged rs1876828, rs242939 and rs242941 SNPs of the CRHR1 associated with genetic risk to depressive disorders were genotyped. A cut-off score of 10 was used to detect increased risk of PND. Association analysis was carried out in 140 patients that completed the study protocol. The BClI and rs242939 SNPs were over-represented in women with postnatal EPDS score >= 10 with significant allele association (p = 0.011 and <0.001, respectively) and risk ratios of 2.9 (95% CI: 1.2-6.9) for BclI, 4.9 (2-12) for rs242939 and 5.48 (2.13 -14.10) for both. The rs242939 SNP was also associated with increased EPDS values during pregnancy. Moreover, the G-G-T haplotype of the CRHR1 was significantly over-represented in patients with high EPDS scores, with risk ratio of 3.22 (95% CI: 1.91-5.42). This is the first evidence that specific SNPs of genes involved in 'stress' responses might contribute in the genetics of high-risk for depression during pregnancy and postpartum.

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Journal of Psychiatric Research
Publisher: Pergamon
ISSN: 0022-3956
Official Date: September 2013
Dates:
DateEvent
September 2013Published
3 June 2013Available
6 May 2013Accepted
29 December 2012Submitted
Volume: Volume 47
Number: Number 9
Page Range: pp. 1166-1173
DOI: 10.1016/j.jpsychires.2013.05.003
Status: Peer Reviewed
Publication Status: Published

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