>> DR.
PETER SCHMIDT: So many women will report experiencing feels of irritability, sadness, anxiety -- during
the luteal phase, or the premenstrual phase of their cycle.
As those concerns have been investigated, we've realized that perhaps two to five percent
of women who experience these symptoms during the luteal phase will experience a very a
very marked disability and dysfunction associated with that.
And it was very clear that there was no abnormality of any reproductive hormone that distinguished
a woman with Premenstrual Dysphoric Disorder from a woman who had no symptoms during her
luteal phase.
These women would experience a remission of their symptoms when ovarian function was turned
off -- and then a recurrence of symptoms when either of the hormones was added back.
Women with PMDD experienced a differential sensitivity to the mood disturbing effects
of ovarian steroids.
So there was no abnormality of these hormones.
What was abnormal was the behavioral response to normal levels of these ovarian steroids.
We essentially tried to recreate what we saw in the clinic in the laboratory.
>> DR.
DAVID GOLDMAN: Drawing the blood from these women and making cell lines, we then have
a type of -- if you will -- disease in a dish.
Or a little model of the human patient in a dish that we can study molecularly.
And, so then those cells were studied both at baseline and after treatment with ovarian
steroids, mimicking the sort of changes that occur in a woman during the ovarian cycle.
And showing that at baseline, and also after exposures, that they are intrinsically different
in a pathway involved in ovarian steroid response.
Some women's cells respond differently to ovarian steroids than do others.
Rather than homing in on what we already know, which are receptors for ovarian steroids and
some of the ovarian steroid response apparatus -- the usual suspects, if you will -- we study
simultaneously the expression of thousands of genes.
And then, via gene network analyses, identify the particular networks that are distinct
and different in the cases versus the controls.
And when this was done, it was quite exciting that a main molecular network that came up
was an ovarian steroid response gene network.
It had never been noted before that in women with PMDD that that pathway was systematically
disturbed in any way.
So the discovery was made in a genomic context, but it did lead back to a destination that
we might have expected.
What we're now doing is that we're improving on this lymphobastoid cell model with induced
induced pluripotent stem cells made from these very women.
So these are a cell line, again made from cells in peripheral blood, which are capable
of becoming, capable of developing into any type of cell that we could want to study.
And, in particular, we're able to take these induced pluripotent stem cells and were able
to stimulate them to develop into neurons.
And then these neurons will be able to study in detail and, hopefully, to confirm these
sorts of findings that we've made in the lymphoblastoid cell lines.
>> DR.
PETER SCHMIDT: So, once we identify either the mechanism where they're stimulated or
their direct action on other genes, that will open up the opportunity of transforming the
abnormal cellular response to steroids into a normal one.
And hopefully will provide women with PMDD with some alternate therapies that may be
based more directly on the cause of the condition.