Genetic variation of the hypothalamo-pituitary axis may increase susceptibility of postnatal depression

N. Engineer; L. Darwin; N. Deole; K. Ngianga-Bakwin; S. Smith; D. Grammatopoulos

Objective: To investigate whether genetic variants in the glucocorticoid receptor (GR) and corticotropin releasing hormone receptor 1 (CRHR1) genes are associated with increased susceptibility for postnatal depression (PND).

Methods: A prospective longitudinal cohort study at University Hospital, Coventry, England. Two hundred pregnant women were recruited and assessed for PND using the Edinburgh postnatal depression score (EPDS) upon recruitment and again 2–8 weeks post-natally. Five SNPs with established association to depression were genotyped. Association analysis was carried out in 140 patients that completed the study protocol.

Results: The bcl1 SNP of the GR and rs242939 SNP of the CRHR1 genes were over-represented in women with PND with significant allele association. Risk ratios for development of PND associated with presence of each minor allele were 2.9 (95% confidence interval: 1.2–6.9) for bcl1 and 4.9 (2 to 12) for rs242939. In contrast, no significant association was found between PND and the R23K, rs1876828 or rs242941 SNPs.

**Table 1** Patient demographics and single nucleotide polymorphism distribution in the study population
Variable	Cases without postnatal depression number (%)	Cases with postnatal depression number (%)	P value
Total number	106 (75.7)	34 (24.3)
SNPs Bcl1 HET/HOM WT	51 (48.6) 54 (51.4)	25 (73.5) 9 (26.5)	0.011*
R23K HET/HOM WT	9 (8.6) 96 (91.4)	2 (5.9) 32 (94.1)	0.61
rs1876828 HET/HOM WT	34 (32.4) 71 (67.6)	14 (41.2) 20 (58.8)	0.35
rs242939 HET/HOM WT	13 (12.4) 92 (87.6)	14 (41.2) 20 (58.8)	0.003**
rs242941 HET/HOM WT	62 (59.6) 42 (40.4)	26 (76.5) 8 (23.5)	0.076
Het/hom, Heterozygous/homozygous allele, WT: wild type allele.

Figure 1. Forest plot for glucocorticoid and cortico tropin releasing hormone single nucleotide polymorphisms.

Conclusions: This is the first demonstration that specific SNPs of the GR and CRHR1 genes are associated with PND and might represent promising genetic biomarkers to help early identification of women at risk of PND.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Endocrine Abstracts

P1101