Maternal Inflammation and Baby’s Brain - Claudia Buss, Ph.D.
>> DR. CLAUDIA BUSS: I'm particularly interested in the fetal origins of psychiatric disorders. And what has been acknowledged more and more is that it's really the very early environment -- and as early as the intrauterine environment -- that plays a fundamental role in determining disease susceptibility in an individual. And this is has been supported, for example, by studies showing that maternal infection and inflammation during pregnancy actually increases the risk for psychopathology, like schizophrenia, but also autism, in the offspring. And what we are really interested in are what might some of the biological determinants -- the biological alterations during pregnancy that might be modifiable by interventions -- that program the fetal brain. We do this by recruiting women in their very early pregnancy -- mid- first trimester -- and follow them over the course of gestation to get measures of stress biology. We're looking into inflammatory markers. So immune mediators that are elevated under conditions of infection, but also under conditions of stress. for example. We start assessing the infants right after birth. What we see is really the result of the prenatal environment, in interaction of course with somatic susceptibility -- and not yet confounded by post-natal influences. So we obtain MRI scans shortly after birth. And we look at brain anatomy. But also structural and functional connectivity. And then we follow up the children further and do another MRI scan at 12 months and at 24 months to look at developmental trajectories. And then we also try to get good estimate of the quality of the post-natal environment, which will also affect brain development. Because the brain stays highly plastic after birth as well, of course. Specifically, what we focused on was maternal interleuken 6 concentrations during pregnancy. This is a pro-inflammatory cytokine, an immune mediator that's -- as I said -- elevated under conditions of infection and inflammation, but also under conditions of maternal obesity, for example -- and also under conditions of maternal stress. All conditions that have been associated with an increased risk for psychopathology in the offspring. So we, for the first time, measured directly interleuken 6 in pregnant women and then related it to newborn brain maturity. And what we focused on in the newborn brain was functional connectivity. So we obtained a resting state fMRI scan. So basically what we're doing is looking at activity in the newborn's brain. We're scanning them during natural sleep. And we're looking at which brain regions are active together. We are looking for synchronized activity. If two brain regions are active together, there must be some connection so they can talk to each other. So it's really based on the principle "what wires together fires together." So we can really think about how might those conditions that we know can influence interleuken 6 concentrations during pregnancy -- maternal depression, maternal stress -- and maybe think of some multimodal interventions that affect these conditions. And hopefully normalize interleuken 6 concentrations, because it seems to affect fetal brain development. We still need to learn more about what kind of conditions during pregnancy actually are associated with alterations in interleuken 6 concentrations. And then to see whether, as we modify those conditions, we also modify interleuken 6 concentrations. I don't think we're at the point where we would even want to start thinking about any kind of pharmacological interventions. Because interleuken 6 is critically important for normal brain development, as well. So we definitely wouldn't want to block it. So we still have to learn much more about what are levels where there seems to be really adverse outcomes on the fetal brain. And until then, I think one should start targeting those conditions in the mother that have been shown to elevate interleuken 6 concentrations during pregnancy.