--- title: Can an estrogen and gene variant cause PMDD-like mood symptoms? description: Mice carrying a BDNF gene variant developed anxiety and depression-like behavior when given estrogen, similar to PMDD symptoms. url: https://niyora.com/research/papers/epigenetic-intersection-of-bdnf-val66met-genotype-with-premenstrual-dysphoric-2020/ --- - [Niyora](https://niyora.com/) - [Research](https://niyora.com/research/) - [Library](https://niyora.com/research/library/) - Can an estrogen and gene variant cause PMDD-like mood symptoms? Lab study, 2020 # Can an estrogen and gene variant cause PMDD-like mood symptoms? Mice carrying a BDNF gene variant developed anxiety and depression-like behavior when given estrogen, similar to PMDD symptoms. Early or limited evidence Ovariectomized mice with or without a BDNF gene variant ## What they did Ovariectomized mice with and without a BDNF gene variant were given estradiol in drinking water for 6 weeks or placebo. Researchers tested their anxiety and depression using behavioral tests and measured gene expression in the brain. ## What they found Estradiol caused anxiety-like and depression-like behavior in mice with the gene variant but not in normal mice. Gene expression patterns in the treated mice with the variant matched patterns seen in women with PMDD. ## What it means for you This suggests that a combination of a specific gene variant and estrogen exposure might trigger PMDD-like symptoms. The genes involved control how cells respond to estrogen. The main limit is this is a mouse study, and PMDD affects over 5% of women, so many factors besides this one gene are likely involved. over 5% Percentage of women affected by PMDD 6 weeks Duration of estradiol treatment ## About the study Original title Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back Authors Marrocco J, Einhorn NR, Petty GH et al. Journal Molecular psychiatry Year 2020 Study design Lab study What was tested Estradiol in drinking water for 6 weeks Open access Yes Read the paper [doi.org/10.1038/s41380-018-0274-3](https://doi.org/10.1038/s41380-018-0274-3) Original abstract Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms similar to anxiety and major depression, and is associated with differential sensitivity to circulating ovarian hormones. Little is known about the genetic and epigenetic factors that increase the risk to develop PMDD. We report that 17β-estradiol (E2) affects the behavior and the epigenome in a mouse model carrying a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD. Ovariectomized mice heterozygous for the BDNF Met allele (Het-Met) and their matched wild-type (WT) mice were administered estradiol or vehicle in drinking water for 6 weeks. Using the open field and the splash test, we show that E2 add-back induces anxiety-like and depression-like behavior in Het-Met mice, but not in WT mice. RNA-seq of the ventral hippocampus (vHpc) highlights that E2-dependent gene expression is markedly different between WT mice and Het-Met mice. Through a comparative whole-genome RNA-seq analysis between mouse vHpc and lymphoblastoid cell line cultures from control women and women with PMDD, we discovered common epigenetic biomarkers that transcend species and cell types. Those genes include epigenetic modifiers of the ESC/E(Z) complex, an effector of response to ovarian steroids. Although the BDNF Met genotype intersects the behavioral and transcriptional traits of women with PMDD, we suggest that these similarities speak to the epigenetic factors by which ovarian steroids produce negative behavioral effects. Reproduced under CC-BY. ## Topics [Premenstrual dysphoric disorder (PMDD)](https://niyora.com/research/topics/condition-pmdd/)[Low mood and depression](https://niyora.com/research/topics/symptom-depression-mood/)[Anxiety and tension](https://niyora.com/research/topics/symptom-anxiety/)[Major depressive disorder](https://niyora.com/research/topics/comorbidity-major-depression/) Research tells you what helps on average. Niyora helps on the day it hits. Calm down, see it another way, and decide what to say, with a PMS and PMDD app built by a doctor. ## Related studies Non-randomised trial, 2008 Can the Sheehan Disability Scale measure whether treatments work? Study, 2026 Do anxiety and depression get worse before your period if you already have a mental health condition? Study, 2026 What are premenstrual syndrome and premenstrual dysphoric disorder? Review, 2014 Are mental health problems linked to gynecological conditions like PMS and PMDD? Cohort study, 2012 How quickly does fluoxetine start working for PMDD symptoms? Randomised trial, 2004 Does paroxetine controlled-release help PMDD symptoms? Ask AI about this page Copy prompt ChatGPT ↗ Claude ↗ Perplexity ↗ Google AI Mode ↗ Grok ↗