Glucocorticoid receptor gene haplotype predicts increased risk of hospital admission for depressive disorders in the Helsinki birth cohort study.

Background: Although glucocorticoid receptors (GR) are involved in mediating hypothalamic-pituitary-adrenal-axis functioning, which is altered in acute depression, data on associations between GR gene (NR3C1) polymorphisms and depression are scarce. We examined if single nucleotide polymorphisms (SNPs) and their haplotypes spanning the entire NR3C1 are associated with depressive disorders and with self-reported depressive symptoms in adulthood.

Methods: We successfully genotyped 10 SNPs spanning the NR3C1, and performed SNP and haplotype analyses in 1,075 women and 928 men participating in the Helsinki birth cohort study. Diagnoses of depressive disorders were extracted from the Finnish Hospital Discharge Register covering a 35-year period from early to late adulthood. In addition, depressive symptoms were self-reported with standardized questionnaire in late adulthood.

Results: In comparison to the most common haplotype, one haplotype in the regulatory region of the NR3C1 was associated with increased risk of hospital admission (OR: 3.35; 95% confidence interval 1.5 to 7.3) for depressive disorders after adjusting for sex, birth year, and education. The association was statistically significant after Bonferroni correction for multiple testing. There were no other significant associations.

Conclusions: Haplotypic variation in the regulatory region of the NR3C1 may increase vulnerability to depressive disorders requiring hospital admission, but is not associated with self-reported symptoms.