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Male Vulnerability to Maternal Stress Linked to Placental Enzyme

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NIMH grantee Tracy Bale, Ph.D., of the University of Pennsylvania, discussed her line of research into how maternal stress might differentially affect the developing male brain during an interview at the 2011 Society for Neuroscience meeting.

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Transcript

Dr. Tracy Bale: Many of our neuropsychiatric diseases have a very strong sex bias. For instance, autism is 4 to 1 – actually now it’s more than 4 to 1 – boys to girls. Why is that? What’s been thought likely, for many years now, is that there must be some fetal antecedent. Meaning, some perturbation during pregnancy, especially for neurodevelopmental disorders, that either takes in contribution of your genetic predisposition and adds to it an environmental sort of push – or maybe that environmental push itself is the genetic predisposition.

What is experienced during very plastic periods of development can end up altering – and we call this epigenetic, because it is not changing your gene sequence. It is just modifying the way in which those genes are expressed. This is very important for understanding how the brain develops, and how, later in life you’ll respond to different perturbations yourself that may predispose you toward disease.

What we don’t have in any neurodevelopmental disorder is biomarkers. We really don’t have any way to determine which child may be predisposed to presenting with, or developing, schizophrenia or autism. We have no idea. So our hope is that when we expose mom to stresses while she’s pregnant, that if we could find changes in proteins or gene expression or epigenetic marks that are either sex-specific or in response to stress. We’re looking within amniotic fluid and in the placenta. And the reason we’re looking there instead of the brain, is because it’s obviously much more translatable. You cannot, obviously, go into a baby’s brain – nor would we want to – and look at these changes. What we can do: it’s very easy to gain access, if you thought that there was a reason – that a mother had experienced a trauma in pregnancy and you wanted to know. So we’re looking for markers in the mice that would be relevant – and hopefully, we could then look in humans and say yes, these are the same proteins. There are sex differences. These are affected by stress. And they may be predisposing – or at least markers of an indication that mom experienced some sort of trauma during pregnancy that could then lead to a change in the offspring’s brain development.