The complex interaction between oestrogen receptor genes, oestradiol, and perinatal mood

Genetic variations in oestrogen receptor (ER) genes are associated with inter-individual differences in the sensitivity of ER-α, ER-β and G protein-coupled oestrogen receptor (GPER). These sensitivity differences may modulate susceptibility to mood changes during phases of endogenous oestrogen fluctuations, thereby explaining individual vulnerability. This study examined the association between ER gene variations, oestradiol and perinatal mood disturbances.

A total of 159 women were observed during the perinatal period, providing saliva samples for oestradiol assessment and completing self-report measures of depressive and anxiety symptoms at five time points. Polymorphisms in ER genes were determined from dried blood spots. The associations were analysed using linear mixed models.

The ER-α gene haplotypes were associated with perinatal mood disturbances. The CG haplotype was associated with perinatal depressive (p = 0.0162, F-test) and anxiety symptoms (p = 2.396e-05, F-test), whereas the TA haplotype was associated with perinatal anxiety symptoms (p = 0.004, F-test). The interaction between ER gene variations, oestradiol and perinatal mood disturbances was not significant.

ER-α gene variations are associated with an increased susceptibility to perinatal mood disturbances. Sensitivity differences in ER-α appear to play a more important role for emotional processes than those in ER-β and GPER, independently of oestradiol levels. This might be explained by ER-α's more dominant expression in the hypothalamus and amygdala.