Estrogen receptor alpha (ESR-1) associations with psychological traits in women with PMDD and controls

Abstract

Premenstrual Dysphoric Disorder (PMDD) is a mood disorder affecting about 5% of women and is associated with substantial morbidity. Albeit inconsistently, PMDD is described as being characterized by heritable personality traits. Although PMDD is a heritable disorder, it is unclear whether any of the heritable susceptibility to PMDD resides in heritable personality traits. In groups of carefully characterized women with PMDD (n=68) and controls (n=56), we attempted to determine whether diagnosis-related traits could be confirmed, as well as to determine whether such traits were associated with SNPs in estrogen receptor alpha (ESR-1) that we previously demonstrated were associated with PMDD. We observed 7/25 traits to be significantly different in patients and controls and further showed that 11/12 significant associations observed between these 7 traits and 16 ESR-1 SNPs involved the intron 4 SNPs previously shown to be the locus of the association with PMDD. While several interactions between genotype and diagnosis were observed, the effect of genotype in most instances was in the same direction in patients and controls. These data demonstrate affective state-independent personality traits that distinguish patients with PMDD from controls and further support the relevance of ESR-1 polymorphic variants in the regulation of non-reproductive behaviors.

Figure 1

Error Bar: +/− 1 SE Three sample comparisons of psychological traits in subjects homozygous for the major allele (1/1) with those in whom a minor allele was present (1/2, 2/2) in patients with PMDD and controls. Impression Management scores are lower in subjects carrying the minor allele in both the PMDD and control samples (genotypic effect, F₁=4.04, p=.05). The opposite effect is seen with Abstractedness and Harm Avoidance (genotypic effects, F₁=6.82, p=.01 and F₁=6.77, p=.01, respectively). In both samples, the subjects carrying the minor allele have higher scores compared with those homozygous for the major allele in both the PMDD and control samples.

Figure 2

Error Bar: +/− 1 SE Two representative examples of the interaction effects between genotype and diagnosis (PMDD vs controls) on psychological trait scores. (A) Although the Emotional Stability scores of the controls do not change with genotype, the PMDD subjects who are carrying the minor allele show decreased Emotional Stability scores (F₁=5.17, p=.03). (B) A similar trend appears with Neuroticism. Control subjects maintain similar scores regardless of allele, while PMDD subjects who carry the minor allele have increased Neuroticism scores (F₁=4.76, p=.03).