--- title: What is actually happening: what the research says ยท Niyora description: What is going on in my brain? Genes, GABA, serotonin, and the add-back studies. This is the best-evidenced part of the whole picture. url: https://niyora.com/research/mechanism/ --- [Research](https://niyora.com/research/) # What is going on in my brain? Genes, GABA, serotonin, and the add-back studies. This is the best-evidenced part of the whole picture, and the reason none of this is in your head. 5 findings. Best evidence here: **strong**. ## What is actually happening - strong PMDD Your hormones are completely normal. The difference is how strongly your brain feels the shift. Same hormone levels in women who feel awful vs fine; the difference is brain sensitivity to normal shifts (~56% heritable) [Schmidt/Dubey](https://pmc.ncbi.nlm.nih.gov/articles/PMC10176022/) - strong PMDD The calm chemical your body makes from progesterone drops before your period, and sensitive brains feel that withdrawal. Add-back paradigm ties symptoms to GABA / allopregnanolone (progesterone metabolite) withdrawal ["Genes to GABA" review](https://pmc.ncbi.nlm.nih.gov/articles/PMC10176022/) - strong PMS / PMDD When estrogen dips after you ovulate, serotonin dips with it, and your calm system gets thrown off. Review: luteal estrogen drop lowers serotonin; reduced allopregnanolone sensitivity -> GABA/glutamate imbalance + HPA activation [Zinc/Cu/Mg review](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647176/) - moderate PMDD A big part of how strongly you feel this is inherited. GWAS: premenstrual symptom heritability ~35-57% [GWAS 2025 preprint](https://www.medrxiv.org/content/10.64898/2025.12.01.25341208.full.pdf) - moderate PMDD Researchers can see the difference in your actual cells and blood flow. Cellular Ca2+/ER-stress + brain-blood-flow studies support the ESC/E(Z) sensitivity finding [ESC/E(Z) follow-ups](https://www.nature.com/articles/s41380-021-01144-8) The grades are mine, applied the same way to every row. [See how I grade](https://niyora.com/research/) and read the rest of the table. ## Keep reading [PMS anxiety](https://niyora.com/pms/anxiety/) ## Knowing why only helps if you can use it Niyora turns this into three steps for when it actually hits. Reflect on what happened, regulate in about a minute, respond with a clearer head. [Take the quiz](https://niyora.com/quiz/) [Get Niyora](https://apps.apple.com/app/niyora-pms-emotions/id6764561688)