Potential role of the estrogen receptor gene (ESR1) in anxiety

In addition to neurotransmitters, hormones, acting through the blood stream, also play a role in behavior. To test the potential contribution of genetic variations in hormone receptors we have examined the association between the alleles of the dinucleotide repeat of the estrogen receptor 1 gene (ESR1) and the nine subscores and total score of the SCL-90 in a group of 179 adult males treated for substance abuse. Based on our prior hypothesis that the length of repeat polymorphisms may play a direct role in gene regulation, the alleles were divided into two groups, short (S) and long (L). ANOVA of the SS, LS, and LL genotypes showed a significant association at α ≤0.05 for three of the SCL-90 scores: anxiety, phobic anxiety, and total symptoms. Of these the anxiety score remained significant at a Bonferroni corrected α of ≤0.005. By regression analysis, the ESR1 gene accounted for 7% of the variance of the anxiety score (P ≤ 0.0004). These results are consistent with a role of the ESR1gene in human behavior. Since estrogen levels are much higher in women than men, this could account for the increased frequency of anxiety in women.