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12-09-2011 | Mental health | Article

NR3C1 gene SNPs linked to depression predominance in BD


Free abstract

MedWire News: Three single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene NR3C1 are significantly associated with major depressive disorder (MDD) and depression predominance in patients with bipolar disorder (BD), research shows.

Writing in the Journal of Affective Disorders, Aleksandra Szczepankiewicz (Poznan University of Medical Sciences, Poland) and team observe that "dysregulation of hypothalamus-pituitary-adrenal (HPA) axis has been well documented in several psychiatric disorders, including affective disorders."

They add that the glucocorticoid receptor plays an import role in HPA axis regulation, "and its gene has been recognized as a candidate gene for major depressive disorder and bipolar disorder."

To investigate further, the researchers studied 514 patients with BD, 193 with MDD, and 732 controls without a history of serious mental illness.

All of the participants were genotyped for eight NR3C1 SNPs, namely rs41423247, rs6195, rs10052957, rs6198, rs6191, rs258813, rs6196, and rs33388.

The researchers found that the CT genotype of rs6198 and the AA genotype of rs6191 were significantly associated with an increased risk for MDD, whereas the TT genotype of rs33388 appeared to be protective against MDD susceptibility.

Overall, there were no significant differences in genotype or allele frequencies between BD patients and controls.

However, regarding bipolar phenotype, the researchers found a significant association between the rs6198 SNP and an increased risk for depressive episode predominance over manic/hypomanic episodes. The AA genotype of rs6191 was also significantly associated with an increased risk for depressive episode predominance, whereas the rs33388 SNP had marginal significance in this respect.

Szczepankiewicz and colleagues conclude: "Our findings indicate that NR3C1 polymorphism[s] may influence susceptibility to MDD and seem to influence the predominance of depressive episodes in the course of BD.

"However, additional factors influencing glucocorticoid sensitivity and therefore depression development should be also taken into account in future research on susceptibility to BD and MDD."

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Mark Cowen

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