In the late 1990s, we were able to demonstrate that PMDD was not a hormone deficiency disorder but rather a hormone sensitivity disorder; i.e., normal levels or changes in reproductive steroids (estrogen and progesterone) triggered the symptoms of PMDD but did so only in a subgroup of women who, for unknown reasons, were sensitive to these hormonal changes. We subsequently demonstrated the same phenomenon in women with a history of postpartum depression. We showed, therefore, in two mood disorders – PMDD and PPD – that changes in hormone levels that had no effect at all on mood in most women were capable of triggering substantial mood changes in a subgroup of women. But what was responsible for this differential sensitivity? We now have at least a partial answer.
In the January issue of Molecular Psychiatry, Neelima Dubey, Jessica Hoffman and colleagues demonstrated that the cells of women with PMDD differ from those without PMDD in both their baseline functioning and in their response to estrogen and progesterone. These findings show that an important family of genes that regulate the response to both the internal and external environments are more active in women with PMDD and, of greater interest, respond differently when the cells are exposed to estrogen or progesterone. In other words, the cells themselves were differentially sensitive to reproductive steroids, just as women with PMDD show differential behavioral response to changes in reproductive steroids. These findings are important for three reasons: 1) they demonstrate a biological basis for PMDD; and 2) they may help us identify targets for developing effective therapies; and 3) they provide clues to help us understand how a biological signal may be transformed into a change in mood and behavior.
David R. Rubinow, MD