How pregnancy affects the mother's brain

Detailed brain scans of a mother before, during and after pregnancy have revealed stark changes in the size and connectivity of many brain regions, particularly those related to socialisng and emotional processing. The study - which has been published in Nature Neuroscience - claims to be one of the first comprehensive maps of the brain during the 9 month gestation period, and with some 85% of women falling pregnant at some point in their lives, some say proper research in this area is long overdue. Scientists suspect the changes relate to a pruning down of connections within the brain, perhaps optimising the way some brain areas communicate with one another, possibly facilitating mother-baby bonding or caregiving. Here to tell us more is lead author Laura Pritschet, post doctoral fellow in the department of psychiatry at the University of Pennsylvania.

Laura - What we know thus far in the existing literature is based on experiments that have done sort of a snapshot approach where we have taken women before they're going to try to become pregnant and scan their brain looking at a bunch of details of their grey matter, their white matter, fluid in their brain. And then we will bring them back and scan them again early postpartum when they've just delivered. And that is really interesting and it provides the strongest evidence to date that neural changes are happening from that time where they're trying to become pregnant to delivering a baby. There are these grey matter reductions from pre to post pregnancy and those reductions can persist up to six years postpartum. And that includes cortical grey matter volume, it includes the thickness of the cortical sheet, which is that outer layer of the brain. But the outstanding question was, what does that pace of change, what does that time course of those reductions, look like?

Chris - Indeed. And is it uniform across pregnancy or are there surges in cortical loss, and then it settles down? So how did you actually go about doing this and who did you study?

Laura - What we've done in the last decade or so is really put that spotlight back on the individual asking, are we representative of ourselves at a single time point? And in fact, that temporal flow, those fluctuations in our day-to-day life could be reflected in the brain. And that's not something we're capturing. And so they've turned to this sort of precision imaging dense sampling approach where now we're bringing in fewer samples of people, but scanning them and studying them over long periods of time and getting a lot of phenotypic data on them. Meaning we can study their mood, we could get their blood, we can ask them a tonne of questions and get a lot of information on the individual. And we thought that is the perfect model to explore some of these hormone related questions we have for the brain because the brain itself is a dynamical system. It's not static. It's ebbing and flowing. And so are hormones. And at that time, we had a colleague of ours come to us and say, look, I'm going to be family planning soon. And what if we took that approach and scanned myself throughout this whole journey? So we had a volunteer, she's the co-senior author on this paper, Liz Chrastil, she's a professor at the University of California Irvine. And we scanned her brain three weeks before she began IVF all the way through two years postpartum.

Chris - Was this with MRI? Magnetic resonance imaging?

Laura - Yes. A 30 to 45 minute brain scan with MRI.

Chris - And this enabled you to get the gross anatomy? What did that show you? Was there any particular hotspot in pregnancy when things changed or was it just a gradual change? And if you map that onto what's happening to her hormones, is there a correlation?

Laura - Yes. All great questions. And actually, the answer differs when you think about different metrics of brain anatomy. So with respect to starting with grey matter volume, the brain metric that has been studied the most, this is where the cell bodies live, the neurons, we found this sort of linear decline. Grey matter volume was reducing as gestational week was advancing and sex hormones were rising. That was pretty widespread. 80% of the brain regions we looked at showed that sort of relationship. There wasn't any sort of big inflection point. And then in postpartum, those grey matter volume reductions bounced back a little bit, but they did not return to baseline levels. And we see the same pattern for cortical thickness. So you've got the actual volume, the area within those regions, and you have the thickness of the cortex itself. Those are really tied metrics to each other. However, at the same time, you can think of this as, well, if a tissue in my brain is reducing, something's got to fill that space <laugh>. We are not walking around with these sort of holes in our brain. And that's what we saw. We saw cerebral spinal fluid increase over pregnancy. We saw lateral ventricles expand during pregnancy. And it just shows this beautiful choreographed dance of what's changing over this period. Now, one of the most interesting, and I would argue novel findings here, is that we also had our subject do what we call as a diffusion imaging scan, which allows us to capture information on white matter tracts in the brain, which is the myelinated axons that are facilitating communication between neuron A and neuron B. And what we found is that the integrity of that white matter was increasing over pregnancy and it peaked in the second trimester. So it showed sort of a non-linear rise over pregnancy. And again, there are some caveats to us talking about those inflection points and pace when we're speaking about only a single subject. But that is very interesting to us because, of the articles that have looked pre to post pregnancy and done those same sorts of metrics looking at white matter microstructure, they didn't find any differences. And that could be due to us not capturing that big metamorphosis in the brain because we didn't look within gestation itself.

Chris - Does this give us any clues then as to what might be going on for the fraction of women who, after they've had a baby, can develop really profound mood disorders like the baby blues, for example, or even some psychiatric conditions which are much more likely to manifest in that period?

Laura - Yeah, this is the million dollar question. I think what we're trying to do right now is say, okay, right now we're going to tackle this. It's a basic science question. Let's bring a lot of people in. Let's create this normalised map like brain charting over pregnancy to establish what that pace looks like across a demographically enriched cohort of people. Then we can go in and say, okay, well do deviations from that pace itself lead to these sorts of divergent brain outcomes. And then additionally, we need to find markers, biomarkers, of the subsample of women who are at highest risk for perinatal and postpartum depression. We know that some women are really sensitive to those hormonal fluctuations, others are not. And what I find to be some of the most interesting takeaways from our work in the existing literature is that areas of the brain that show the biggest amount of change pre to post pregnancy overlap with depression circuitry. Now, that doesn't mean everyone goes on to have depression in the postpartum period, but that means that that's a sensitive circuit to hormones. And let's start to model this with, did they have exposure to IVF? Did they have a history of reproductive related psychiatric issues? And how is their brain responding to these hormonal changes during pregnancy? And I think those are some of the most pressing questions in human health.