Could variations in a stress-hormone receptor gene be linked to fewer manic episodes in bipolar disorder?

Details

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is frequently observed in affective disorders. The researchers proposed that polymorphisms in the glucocorticoid receptor (GR) gene, NR3C1, might subtly change receptor functioning, potentially contributing to altered HPA-axis responses to stress and, subsequently, to the development and course of affective disorders. The study aimed to evaluate associations between GR gene polymorphisms and bipolar disorder (BD).

In this observational case-control genetic association study, 245 patients with BD were interviewed to confirm their diagnosis and BD subtype. Medication use and sociodemographic details were also collected. The control group comprised 532 healthy blood donors, for whom sex and age data were collected. Blood was collected from all patients and healthy controls for genotyping.

The researchers reported a trend toward a protective effect on disease manifestation for the exon 9beta polymorphism (p = 0.14) and the TthIIII polymorphism (p < 0.05). Male sex significantly influenced these effects for both polymorphisms. Patients with BD who carried the A/G variant in exon 9beta had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found between the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons.

The researchers concluded that the exon 9beta and TthIIII polymorphisms of the GR gene may be associated with a protective effect on the clinical manifestation and course of BD. They also concluded that the other studied GR gene polymorphisms were not associated with the disease.