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Transforming the understanding
and treatment of mental illnesses.

Director’s Innovation Speaker Series: Addressing Social Determinants to Optimize Infant Brain Development

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JOSHUA GORDON: We will get started. Hello. Welcome, everyone. I am Dr. Joshua Gordon. I am the director of the National Institute of Mental Health. You are joining us for another installation in our Director’s Innovation Speaker Series. It is really my pleasure to welcome Dr. Cynthia Rogers here today to give us a talk on addressing social determinants to optimize infant brain development.

Before I get started, I just want to remind everyone that following the talk, we will have a Q&A session. If you want to ask a question to the speaker, you may enter it into the Q&A box at any time during the webinar. I will go through those questions and ask them of our speaker at the end.

Do not use the chat box for questions. The chat box is there is you need to contact the event production staff in the event you are having technical difficulties. Please enter the questions only in the Q&A box.

Also a reminder that this webinar is being recorded. The recording will be made available in about two weeks on the NIMH website indicated on your screen. Be sure to share that information with any of your colleagues, friends, or family who might be missing this so that they can watch it at another time.

With no further ado then, it is really my pleasure to introduce Dr. Cynthia Rogers, who is Professor of Psychiatry and Pediatrics at Washington University. Dr. Rogers is a rare breed, a researcher who is trained in child and adolescent psychiatry. She trained at Washington University after completing her medical degree there, which followed an undergraduate degree in psychology from Harvard.

Dr. Rogers is now on the faculty at Washington University where she co-directs the Washington University Neonatal Developmental Research Group. This group is really a powerhouse, a multidisciplinary lab with members across a range of medical specialties, studying the early development of the brain using multimodal magnetic resonance imaging, trying to look at the functional structure and other aspects of how the brain develops and importantly, how it is affected by adverse experiences, including many of the social determinants of health that we know drive a great deal of the likelihood for developing mental illness, including poverty, prematurity, prenatal substance use, and other effects. Dr. Rogers also focuses on racially and socio-demographically diverse populations in this endeavor.

Dr. Rogers serves as the principal investigator of multiple NIH grants, including from this institute as well as NIDA and also wears a number of other hats including Associate Director of the Center for Study of Race, Ethnicity, and Equity at Washington University and for the Intellectual and Developmental Disabilities Research Center.

I also learned in my conversation with Dr. Rogers earlier today that she continues to serve and indeed direct the really important multidisciplinary effort to help serve women who are in the perinatal period, especially those with psychiatric and substance use disorders with the aim of trying to reduce the impacts of the challenges that they face on the mental health of their kids. It is really an admirable effort, a multidisciplinary effort. I am sure we are going to be hearing aspects of that today in addition to her own research.

She has been recognized by numerous awards both locally and nationally, including some from the Association of American Medical Colleges as well as several professional organizations. She serves on the Editorial Boards of Biological Psychiatry and the Journal of the American Academy of Child and Adolescent Psychiatry and is a member of many professional societies, including ACNP and the Flux Society and the American Academy of Child and Adolescent Psychiatry.

Dr. Rogers, it is really a pleasure to have you here today. I am really excited to hear your talk and look forward to the Q&A that follows. Thank you.

Agenda Item: Presentation by Dr. Cynthia Rogers

CYNTHIA ROGERS: Thank you. Thank you so much for that introduction. I am really excited to come and talk with everyone today about the work both research and clinical that we are doing, trying to address social determinants in order to optimize infant brain development.

This is a roadmap of where I am hoping we are heading today. First, just a brief review of social determinants of health and then just some discussion of our work and the work of others, looking at how social determinants impact brain development. And then lastly, I am going to talk about how we here at WashU are trying to do some things to address some of the social determinants of the patients that we treat.

So that we are all starting off with the same background, when we think about social determinants of health, these are typically the conditions or factors that we consider to be really important for health. The Robert Wood Johnson Foundation actually found that these social determinants account for about 75 percent of population health outcomes. For those of us who care about health, it is really important that we are caring about how these social determinants are impacting our patients.

We look at these categories with a little bit more specificity. This slide here just gives you some of the factors that are in the various categories that we think of that are driving health. But one of the things to also really be very upfront about is the impact that racism and discrimination have in these social determinants in determining which patients are really faced with most of these factors and how that is impacting a lot of the health inequities that we know we are seeing in this country.

When asked how these social determinants are impacting their local community, you can see there are indeed differences based on by the race and ethnicity of the respondents. But the other thing to also notice of course is that every category of race and ethnicity here is saying that over half of their communities face with the social determinants. Really it is an important factor for all of our research participants and patients that we see that there are important racial disparities that we have to account for.

Those other slides had social determinants that are categorized in these neat little columns as if they were separate. But what this figure here from Norton and colleagues really highlights how interconnected all of these mechanisms related to social determinants of health in the box in the middle are.

But the other thing that I want to highlight really is twofold. One, again, they are sort of also stating how these things are amplified by racial biases. But the other thing to notice is if you go all the way back to the beginning, it really seems like a poverty is really the start that kicks off exposure to these social determinants. It is really related to most of them.

That is one of the reasons why when I think of social determinants, I really put poverty in the center as the hub of this wheel of various factors that really comprise social determinants and some downstream factors. That is one of the reasons why our lab and a lot of our collaborators here at WashU are really focusing on poverty and how it is impacting the outcomes of the research that we do.

Poverty obviously like I said is extraordinarily important. It certainly is not occurring in a vacuum. Family history and genetics are also really important as well and often in some ways are connected to poverty. But these things really set off exposure both prenatally and postnatally of the developing brain to a lot of factors that we think lead to impaired development and then ultimately in poor outcomes for the child.

When we think about early brain development, there is a significant amount that occurs in the third trimester. This movie here was put together by a former post-doc and now faculty member at IU, Kara Garcia, shows it not only grows in size, but it also really grows in complexity of folding. We know that the gray matter quadruples during this time period. There is neurogenesis. A lot of things are occurring. We really feel that the image of your brain because of its rapid brain growth is more vulnerable to the environment and to the social determinants that these children can be exposed to both in utero and ex utero.

But once they are born, there is still a lot of brain development that occurs in the first few years of life. You can see on the far end here at birth, the brain that is a quarter of the size of an adult and not very myelinated. And then you go through those first two years and by the end, you have a brain that is very myelinated, lot more complexity to folding. It looks much more like an adult brain. This is all happening very rapidly during this time period. The post-natal period is also very important when we think about exposure to poverty and related social determinants.

In terms of biological mechanisms, there have been many that have been posited and some here on this slide. And a lot of our research is investigating some of these biological mechanisms. But I just wanted to highlight there are lots of different potential pathways that can connect poverty and then subsequent psychosocial stress to adverse brain development both prenatally and postnatally.

But I also want to acknowledge that there are things that are not on this slide that are very important too, things like nutrition that is impacted by poverty as well as environmental toxins that very well may impact some of these mechanisms as well as others. It is not only through psychosocial stress necessarily that poverty can impact the developing brain.

Now, in terms of research that has been conducted, this really is a burgeoning area, looking at how poverty is impacting brain development. And most of the work has been done, however, with older age groups. But there have been some that have looked at the infant brain. Here is one from a few years ago that just showed in five-week-old infants, a relationship between socioeconomic status and cortical gray matter with increasing SES, increasing volume.

Here is a similar study that started at five months and it was somewhat longitudinal study. And they looked at trajectories of cortical gray matter volume over time, showing that there were different trajectories by level of socioeconomic status.

This is a much more recent study by Amy Margolis and colleagues. What I found interesting about this study is they took a group of children at age 7 and looked at hippocampal and amygdala volume that I am showing here. And the hippocampus has definitely been one of the structures that has been most implicated in being susceptible to the exposure to poverty.

In this study, what they did is they looked at the income-to-needs- ratio of the family so basically a measure of family income based on size and found that it was the income-to-needs at age 6 months that was most related to the volume of these two structures and not the income-to-needs that occurred later in childhood so potentially suggesting that it is this early exposure that really is impactful for the developing brain.

That brings me to some of the studies that we conduct here at Wash U. We have a whole host of studies looking at various adverse exposures during the prenatal period, some of which are listed here. But I am going to focus today on two of our NIMH-funded studies. One is our study of preterm birth that I direct with Dr. Smyser and then another of what we call our eLABE study, which really focuses on prenatal poverty and stress. The PIs are listed there, and I will talk more about the investigative team in a moment.

As Dr. Gordon mentioned, we really do conduct studies with a lot of typically underrepresented populations within research. I wanted to just highlight some of the sociodemographic of our study cohort. The two studies that I will be talking today – you can see a large representation of black families, a lot that are on Medicaid or in poverty.

And then our last study there is in italics because it has not started. But that is what we believe the demographics of the cohort will be once we start recruiting.

Starting with preterm birth, preterm birth is highly related to poverty. This slide was looking at data from the State of Michigan, but this is true nationally. You can see that in blue are the folks in poverty and that gives you the preterm birth rate over the years. Now this slide suggested that we were really doing a great job with preterm birth, and it was decreasing. But unfortunately, starting the next year, preterm birth has escalated once more.

This was an interesting conceptual figure outlining the potential mechanisms, biological mechanisms any way that it would link poverty to preterm birth. The figure goes on to talk about a potential cycle that links a preterm child to then go on to deliver a preterm as well. But just focusing on the first part, you can see some of the same mechanisms that we talked about on the prior slide, leading to preterm birth.

But when we think about social determinants as well, another important factor in how poverty and preterm birth are linked would be things like lack of access to health care so lack of access to high-quality prenatal care. You are more likely to have complications and things that are not caught and more likely to deliver preterm. Whether or not the biology of that would be the same, yes, but we also want to think distally about some of the health care – issues.

Many of you who are familiar with preterm birth likely know that there are racial disparities in preterm birth rates with black women typically having the highest rate of preterm birth. This interesting study looked at how concerns and stress from racism impacted the preterm birth weight. And interestingly what they found was that it was those moms who had more worry and stress from the impact of racism who were more likely to deliver preterm compared to black mothers who did not have that experience. Another laser beam focus highlighting the impact that racism and discrimination is having – when we think about social determinants. It is not even just the structural racism, but also the stress from racism that likely are leading to disparate outcomes.

What we also know about prematurity is that it really has profound effects on the newborn brain. Here, I am showing you 2D MRI images of the full-term brain and a preterm brain. What I always say is you do not have to be a radiologist to be able to look at these two and see how they are different. They are different in size and shape and in the complexity of the folding. They were both scanned basically around the same age.

When we take these and make 3D reconstructions, what we also see is a lot of variability in not only between the preterm and the full-term but also within the preterms as well. But nevertheless, it is very obvious here just looking at five of our participants of how different they are from the full-term brain and then how similar the full-term brain is to an adult brain and how different the preterms are from that and so really suggesting the potential for having a lot of developmental issues as they age.

And one of those issues that we also know about is that prematurity increases the risk of psychiatric disorders, which is one of the reasons why as a child psychiatrist, I was interested in this population. We have known for a while that prematurity increases the risk really of all psychiatric disorders in childhood, but particularly ADHD, anxiety, and autism spectrum disorder, which has led some to develop the term the preterm behavioral phenotype that is made up of these social communication impairments, internalizing symptoms, and attention dysfunction or ADHD or executive function impairment. That is a phenotype that we have been studying a lot. I also see these children clinically and I can tell you that it is definitely a presentation that we see commonly.

For our preemie studies I mentioned, I co-ran the study with Dr. Chris Smyser, a pediatric neurologist here at WashU. And this study has been ongoing since 2007. This slide just kind of outlines the timepoints of the study as well as all of the data that we have been collecting over the years. But today, again, I am going to really focus on some of our imaging data and how it relates to measures of poverty.

While I am sure there is a decent number of imaging folks attending today, I am sure there are others that are not. We often get asked how do you get babies in the scanner and get MRIs. And what I can tell you now that we also scan toddlers and preschoolers and school-aged kids and this is definitely the easiest age group to scan. They are fed, swaddled. They are comfortable. They fall asleep and they sleep through the scan, which his really nice.

In terms of how we measure the neonatal brain, we use common measures that are used in other ages, including resting state functional MRI. I have to thank Chris Smyser for this slide that I think is helpful to explain for those of you who are not familiar. Resting state fMRI or fMRI in general taps the BOLD signal – a signal that is able to measure and that signal varies over time in different regions of the brain. If we are interested in how one particular region might connect to another region, we interrogate that region and say what other regions are temporally having changes in the BOLD signal at the same time as the region of interest. And then we correlate those regions and we get a number.

Here is another representation of that from my medical school classmate, Mike Fox. You can see here that if you look at the warm colors and you are interested in this area here with the green circle, you see these other warm colors are also functionally connected we say to that particular region. While the cool colors if you look down here temporally, you will see the changes are kind of the opposite. That is what we mean when we talk about functional connectivity.

With that, we are able to derive what we call functional brain networks. And these are groups of regions across the brain that are both functionally connected as well and work together for some particular process. The ones at the top are some of the sensory motor functional brain networks. And we typically are more concerned with some of these at the bottom when we think about cognition or psychiatric symptoms.

We are not only interested in function, but we are interested in structure. In addition to getting things like volumes of particular structures, we are also interested in what we call structural connectivity or the microstructure of the brain and we look at things like particular white matter tracks in the brain with diffusion measures, which are explained here on the slide.

But the most important thing is that we are able to look across entire tracks. For us, we are particularly interested in the cingulum here in green and this inferior cingulum bundle in gold, the uncinate here in turquoise and then the fornix in pink. That is because the fornix connects the hippocampus. The uncinate and the cingulum both connect the amygdala prefrontal cortex and those are areas that we are particularly interested in.

Now, I am just going to present some of the results initially linking the medial brain to outcome before I begin the discussion of what we found in relationship to poverty. Here, it just outlines a pregnant woman, an infant, and in our case, a preterm infant, who is born at 27 weeks and then we scan them around the time of their due date, which would have been 40 weeks and then did assessments at ages 2 and 5.

To start off, we looked both at amygdala connectivity and the microstructure of the cingulum bundle. And what we found was that those were related to social skills and attention internalizing symptoms at age 2.

And then Rebecca Brady, a MD PhD candidate in our lab, looked at the cingulum bundle and related that to social skills, internalizing symptoms, and ADHD symptoms at age 5 and found that the neonatal cingulum bundle did predict those symptoms. Again, at age 5, similar to at age 2.

And then more recently, Joe Dust, who is a research staff applying to graduate school as we speak, he then was interested in understanding how some of those functional brain networks that I mentioned during neonatal period relate to social skills and executive function at age 5. And what he found was that particular network, eventual attention network was particularly related to those outcomes in relationship to how it was involved with other networks. Again, the default mode network was another one that popped out particularly with executive function.

That is just a little smattering of some of the work that we have done relating the neonatal brain to outcomes. I want to turn now to some of the work that we have done looking specifically at poverty. While we also look at things like continuance in family poverty, we have been very interested in a measure of neighborhood poverty. Because if we think about social determinants, a lot of it has to do with where you live and where your school is and access to resources.

We have been using the Area Deprivation Index, which was developed by Amy Kind at the University of Wisconsin. It indexes all of these various categories and we are able to obtain a percentile nationally. You can also obtain one for your state. But we have been using the national percentile. And the higher the number, the more neighborhood adversity in that particular area.

This model here just reminds me of all the different regions and structures that we have been really focused on in relationship to the outcomes of interest in the preemie study. We were fortunate to have Bruce Ramphal, who was a student, who worked in our lab under the supervision of Chad Sylvester, our collaborator, looking at poverty in relationship to brain

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CYNTHIA ROGERS: -- as well as some more modest findings with the left amygdala and then the mPFC connectivity to this region, the dorsal anterior cingulate.

For those of you who are not familiar with these regions, the take-home message is that the neighborhood poverty during that prenatal/perinatal period was related to brain connectivity at birth.

We have looked further and found again that the default mode network, which is a network that is implicating a lot of psychiatric disorders was also related to neighborhood poverty.

And interestingly relevant to Bruce’s work, one particular white matter structure of the internal capsule had modest but significant relationship to neighborhood poverty and that is a structure that links structurally the striatum to the prefrontal regions. We found that to be interesting.

With our preemie study, we found some interesting relationships between neighborhood disadvantage and brain outcomes. I should say that we have also and just to summarize quickly found relationships between neighborhood disadvantage and some of those preterm behavioral phenotype symptoms that I spoke of with variances between 14 to 30 percent explained by neighborhood disadvantage.

We have done some analyses trying to see if the brain is mediating those relationships and Bruce did find in the work that he did that that was the case. We are going to continue to look at that within the preemie study.

Now, I am going to turn to a larger study that I mentioned, the eLABE study, Early Life Adversity and Biological Embedding study that is run by Joan Luby, Barb Warner, and Chris Smyser. Deanna Barch, a co-investigator, is on this study as well. This study has a large sample of almost 400 infants. The moms were recruited during the third trimester and the babies are scanned at birth. We collect a whole host of data, some of which is listed here on the slide. But today, I am just going to focus on some of the relationships between socioeconomic disadvantage and the neonatal brain. And most of this is going to be in full-term children since I focused previously on the preterm cohort.

One of the first things we did under the direction of Dr. Phil Miller, a statistician at WashU, was take all of the measures of adversity that we were collecting during the prenatal period and using a data-driven approach trying to see if there were some latent variables that we could derive and we were able to derive both a social disadvantage variable and a psychosocial stress variable. The T1 through T3 indicates the trimester that those things were –

If you think about that wheel of social determinants of health, I think that what you will find is that we assess with particular our social disadvantage variable many components of the social determinants of health. And then with our psychosocial stress variable, we really get more of that social and community context. But today, I am going to focus on the social disadvantage variable.

First, I am going to highlight the work of Dr. Regina Triplett. She is pediatric neurologist at WashU. She is a postdoc with us. She took the eLABE data and found kind of similar to what I showed you before with some of the smaller studies that disadvantaged relates to cortical gray matter. The further left you are there on the bottom of the X-axis, the more disadvantage you have. You can see, again, smaller cortical gray matter volumes. She also found that to be true with white matter as well as cortical surface area depicted here. And she also found it to be true for the amygdala and hippocampus. Really, this was more of a global impact, but that explained a lot of the variances you can see in the volumes in this study.

And then Dr. Rachel Lean, who is a developmental psychologist that worked with us and mentored her on her NIMH-funded career development award. She looked at how prenatal exposure to socioeconomic disadvantage impacted those white matter tracks of the brain that I spoke about earlier and she found that, again, the prenatal exposure to socioeconomic disadvantage impacted the development of all of those white matter tracks.

I also talked to you all about functional connectivity. We talked a little bit about some of our findings with the preterm study. But Ashley Nielsen, who is a postdoc in our lab, was interested in trying to understand how all the different functional brain networks might predict social disadvantage in this cohort. And while she found that really all of them together predict social disadvantage, these five here were the ones that were most predictive.

Now, Rachel was interested in how the functional brain networks were related to social disadvantaged. But she was really focused on those that are more involved with things like executive function. She looked at these particular brain networks and she found that the relationship between these networks was really the most predictive of social disadvantage except for the cingulo-opercular network, which is a network that is basically implicated in almost all psychiatric disorders.

But the other thing to note is they had a lot of overlap in terms of the networks that were involved. Again, this was just two different ways. One was data-driven way with machine learning that Ashley did and then a hypothesis-driven way that Rachel did to really show that that these networks were related to social disadvantage.

Rebecca Brady, who I mentioned earlier, an MD PhD candidate in our lab, was interested in what really can be a very significant exposure when it comes to social determinants and that is the exposure to crime. When you live in an area with high crime, it impacts not only your stress level, your movements, what your child is able to do. She was interested in understanding how that experience during pregnancy might be impacting the developing brain. She was able to get census track level data for our area in St. Louis and compared the crime rates to that of the national average when it comes to violent crime and property crime.

And then using fMRI once more, she was interested in understanding the functional connectivity outcomes in the infants and she found that both the amygdala and thalamus connectivity and thalamic anterior default mode connectivity were related to violent crime while unique to property crime was hippocampus to anterior default mode network. Now, it is important to understand that at least in our city, property crime and violent crime have some differences in terms of where they are distributed. That may impact some of these differences.

But interestingly, what Rebecca was also able to find was that the relationship between crime and particularly the thalamic default mode network connectivity was mediated in part by psychosocial stress that was experienced during pregnancy by the moms. I want to also highlight that she adjusted for social disadvantage. This is over and above the impact of social disadvantage since obviously the experience of violent crime can be highly connected to that.

We have talked about all these findings that we have about poverty being related to the developing brain. But the question is what evidence exists that might be some resilience to these poverty-related brain changes. I think a lot of folks are concerned about stigmatizing children by saying that if you are in poverty, your brain changes. But a very interesting study that used the adolescent and brain cognitive development cohort so 9- to 10-year-olds, about 6000 of the cohort, was interested in understanding how the two networks, the frontoparietal network and the default mode network were related to cognitive test scores. That is because there has been a lot of work suggesting that we engage the frontoparietal network, which is really concerned with things like executive function and cognitive control. And we decrease the default mode network, which has a lot more to do with emotion and internal regulation when we are doing cognitive tests. That is indeed what they found when they looked at the children that were above the poverty line that that relationship that is expected. However, in children that were below the poverty line and they defined or in poverty I should say they defined it as $25,000 for a family of four. They found the opposite relationship. There were kids who were scoring well on the cognitive tests. They were part of ABCD. But their relationship between these two networks was different.

They also found sort of that similar relationship when they looked at proximal factors like neighborhood safety, school type although I do want to make as a public-school graduate, I do want to shout out public schools here. There is a variety and variability in publish schools. It just sort of highlights that maybe there is resilience. There are ways in which your brain is developing optimally for the environment that you are in. There might still be ways that your brain develops that can make you still successful. I think we want to be a little bit circumspect about what some of the changes that we find mean until we can do more longitudinal studies relating the changes that we see related to poverty to outcomes, but not to just stop there, but to also consider as the study did, could there be some compensatory changes in the brain of those who grew up in poverty that still enabled them to have optimal outcomes.

I have talked a lot about some of the research that we do related to the impact that poverty has on brain development. But I think it is important also for us to think about what can we do now that we know. We have known for decades that children that grew up in poverty have a lot of challenges when it comes to development. And now we are increasingly showing through science and policymakers, that this is potentially through changes that we are seeing in the brain. What can we do?

Improving economic stability. That seems like the first thing that you do if you are addressing poverty is to help lift people out of poverty. There is an interesting study that is under review that I am presenting today with permission of authors that is looking at how anti-poverty programs for the kids in the ABCD study, how they might mitigate some of the disparities in brain and behavior.

These are the very states that re represented in the ABCD study. They differ by cost of living and they also differ by how generous the social welfare benefits are. That is one of the things that they were interested in looking at.

What they found was that particularly when you look at kids that were in the higher cost of living areas that if they were in states with more generous social welfare programs that relationship between basically poverty and the hippocampal volume was diminished, meaning that those kids who lived in states with more generous benefits were more resilient in terms of their brain development. That was true also for Medicaid expansion and then an even greater impact on the behavioral outcomes, things like internalizing symptoms, for instance.

This points to the impact that improving economic stability could potentially have. These are school-aged children. There is an ongoing study led by Katherine Magnuson and Kim Noble that is Baby’s First Years that many of you may have heard about that is randomizing or has randomized at this point a thousand low-income women and their newborns to either receive $333 a month or $20 a month for the first 52 months of the child’s life and will be conducting developmental assessments and EEG in terms of assessing brain function. And it will be able to give us some evidence to understand whether or not providing this money is helpful. I should say. They are starting to give the money to the participants once the baby is born.

We unexpectedly got a little bit of a real-world example that is going to impact all of us who do research. Hopefully, all of you that do are definitely taking this into account that for March until this month through the American Rescue Plan, a lot of families, 90 percent of children were receiving the Child Tax Credit. It was expected to lower the number of children that were experiencing poverty by more than 40 percent.

Contrary to what some may say when looked through the CBPP analysis of the US Census Bureau data found that most of those families and that should say 91 were using it on something related to basic needs or education. Obviously, a great benefit. However, that has now expired.

To my colleagues from WashU, Rebecca Schwarzlose and Dr. Joan Luby, who I have mentioned, just wrote an Op-Ed in the Los Angeles Times about why having this child credit end may be doing harm to the developing brain based on some of the research that I have talked about today and certainly in the larger research that is out there.

Thinking about some of the research that folks are conducting now and whether or not we will be able to look at the families that received the Child Tax Credit and how that might have changed brain development for those who received it compared to participants that were recruited before I think will be an important thing for all of us to consider for us to be able to look at some of the policy implications.

We talked about economic stability. And now for those of us in health care. This is the part of the social determinants of health that we can really impact. Health care access and quality. I am going to talk a little bit about some of the things that we are working on and thinking about related to that.

First, this is a figure from a review article that Joan Luby, myself, Deanna Barch, and Tallie Baram did that is intense and similar to also another article that is in press that Joan and myself and Katie McLaughlin did also. Thinking about how can we promote healthy childhood brain behavior development. And one of the ways is talking about how we can get early preventive interventions into routine care and thinking about how as health care providers that that is something that really we should be doing.

And so what I am going to focus on really is this kind of first arrow here, which is enhancing nurturance, sensitivity, and predictability. Joan and her group have published previously in an older pediatric cohort that the relationship between poverty and hippocampal volume was mediated by maternal sensitivity. If we can maybe improve care giving, we will be able to improve the development of the hippocampus.

One of the things as a child psychiatric I know is you cannot really have children develop to their optimal potential if you do not have parents who are functioning well. That led me to start, and I cannot believe it has been 10 years now, a clinical service called the Perinatal Behavioral Health Service, which is focused on providing mental health and substance use care for folks that are pregnant and postpartum period. We have this tripartite model of providing education and screening and then care coordination, including referrals to the community, and then mental health treatment. I show you a little bit more about where we do that.

But the other important part of what we do is we really are passionate about the fact that this should be done in an equitable way, an increasing access to care for those who typically do not receive it. It is something that is really at the core of what we do.

This year I asked Dr. Shannon Lenze to co-director the service with me. And we have a large group of social workers, therapists, and psychiatric clinicians that provide this care throughout the Washington University Medical Center in both our inpatient and outpatient settings. We have co-located within our OB-GYN clinics and we also have started a perinatal opiate abuse clinic in collaboration with our OB colleagues.

What do we do? How do we address social determinants within this program? First, what you see here is a map of our region and the one on the left shows the poverty level of the folks that live there and the one on right shows infanta mortality rates. You can see there is overlap between those not surprisingly. And the purple stars indicate where most of our patients come from. So 55 percent have an income of less than $20,000. Ninety-five percent are on Medicaid. Improving access to that group is very important. We have been fortunate to do that through the funding we have received both from the institution, from community grants as well as from philanthropy.

Also addressing racial equity, which in St. Louis really means increasing access to care particularly for black patients and we know that black perinatal patients are the least likely to have access to mental health care. And those with depression during the perinatal period have increased rates of social adversity. About half of our patients are black and PBHS. We also initiated with our obstetric and pediatric partners, the Women and Infants Equity committee, to really focus on improving outcomes for both the moms and babies in our medical center.

Now this is where some folks stop. But we feel like it is our responsibility to try to assist with basic needs as well. One of the things that was spearheaded by  one of our social workers was to add a food pantry to the OB clinic with our collaboration with John Constantino, our division director, and some others at the Brown School of Social Work here were developing a pilot housing and systems program where we can provide money for some of our patients to be able to utilize to stabilize their housing. And then we make referrals to community agencies from nurse home visitation crisis, nurseries, legal, health, educational resources, whatever the families may need.

And then when it comes to research, Dr. Lenze is our co-director and our close collaborator Ebony Carter recently funded – had a NIMH-funded study partnering with the community to develop novel treatment delivery in the EleVATE study and so embedding mental health into a group prenatal care, really utilizing the patients themselves and helping to design and implement the study. I think this is going to be really helpful with the federally qualified health systems as well as our own OB clinic to really look at how we can improve outcomes in a high-risk population.

I am going to end with some really exciting news in terms of how we are going to address social determinants here at WashU. We were very fortunate to receive a very generous gift from the Hermann family that is allowing us to establish the Hermann Center for Child and Family Development. Thinking about the social determinants of health in our background, we are developing the Hermann Center so that it will have various components, including a two-generation clinical infant program, early psychiatric care program so thinking like preschool years, really robust community partnerships, and then a strong outcomes monitoring and research unit.

Just to highlight the two-generational clinical infant program since we are focusing on infancy today. Providing parental mental health care through PBHS, which I have described already, as well as community resource navigation, parenting education, home visitation, and then child development accounts, which is something one of our colleagues that does Brown School Social Work has really spearheaded and so seeing how all those different components really impact a lot of the social determinants that our families face.

And then the outcomes monitoring and research unit I think will be really valuable looking at not only the baseline risk, but having a community comparison, access to state administrative data linkage is something that we planned and then longitudinal follow-up of these kids so we can really see how a lot of the things that we are doing are impacting outcomes.

I want to make sure we have some time for questions. Just to conclude, I think we have provided evidence that social determinants of heath impact infant brain development. There is some evidence that improving social determinants optimize brain development. But we need more research that is focused on the neonatal period to really understand how the brain is evolving over time and also what the outcomes of these kids will be and again to really look for resilience and compensatory brain changes as well.

Clinical programs can and in my estimation should address the social determinants to improve health. As I mentioned in the very beginning, 75 percent of population health is attributable to these social determinants. If we are interested in improving health either through research or through clinical care, how can we do that if we are not addressing something that is responsible for three-quarters of the outcome. I think it is really important that we embrace this as health systems, as practitioners. And there certainly have been some insurance companies that have shown success in doing that in terms of improving outcomes and decreasing costs. I really think that this is something that we need to more increasingly focus on.

And then last, our mental health advocacy should also include advocating for policies that impact social determinants. I was extraordinarily proud of what Rebecca and Joan Luby did with that Op-Ed. I think that is something that we all need to think about if again we want to improve outcomes. We cannot do that without impacting the things that we know or having such a dramatic effect on our families.

With that, I will end and take some questions.

Agenda Item: Q&A Session

JOSHUA GORDON: Thank you so much, Dr. Rogers. I am applauding on behalf of everyone, who I am sure is also applauding in one way, shape, or form for a really thorough and wonderful integration of what we think about when we think about brain development, what we think about when we think about impacts of social determinants and really trying to understand mechanism and develop interventions that are based upon those mechanisms. I really appreciate the great contributions you made and your articulation of them here. I do see in the Q&A a number of thank yous for the amazing presentations, et cetera, that are echoing my remarks.

But I apologize for not going through more of those and instead I think I will focus on some of the really wonderful and creative questions that came up. One, you have talked a lot about brain mechanisms. You have talked a lot about the social determinants and how they interact on those brain mechanisms. There is one question about other physiological factors. For example, the specific question is does the preemie study include measures of pubertal development or blood and saliva samples for hormonal analysis. I am also thinking about the numerous studies showing impacts of inflammation in pregnancy, other kinds of physiological markers. Can you tell us how they may or may not interact with the mechanisms that you have identified and studied?

CYNTHIA ROGERS: The preemie study does have more questionnaire measures of pubertal, but not hormone measures. But the eLABE study, and I should have made this more clear, has a whole host of biological measures, including multiple inflammatory markers from both the mom and the child. We are looking at the gut microbiome. We have measures of cortisol. A lot of those analyses are ongoing as we are thinking about what are the biological mechanisms linking the exposure to poverty to the brain outcomes. Definitely we think that there is a role or we were trying to see if there is a role for inflammation based on prior data and that is something that we are definitely looking at and literally analyses are ongoing.

We also have saliva for epigenetic assessments and other things. It is a very rich data set and we are really excited about all of the analyses that we are going to be able to do to answer some of these questions with eLABE.

The preemie study was not originally started for the assessment of poverty like eLABE was. It is one of those things where it evolved over time. We are adding measures to it that we think are really important. But that was not what the original goal of the study was.

JOSHUA GORDON: That answers another question that also came in. Is this sample and I assume they are talking about the premature birth sample – all preemie birth or only preemie birth of people in poverty. I think you just answered that.

CYNTHIA ROGERS: We took all-comers who agreed that were in our neonatal intensive care unit. It is just based on where our hospital is located. That is kind of the demographics. We also have a lot of rural poverty that in the study as well because of being a tertiary referral center. It was not focused on only preemies that are in poverty.

JOSHUA GORDON: There are a number of questions that all get at the degree to which you have the power to go beyond the broad measure of poverty and ask about specific other aspects that impact risk. I am just going to name some of the questions that came in. One is around the stress that might be associated with poverty and other forms of stress so maybe mothers with stressful work or family situations, but who are not in poverty situations.

Another one is about the timing of the exposure to poverty or the nature of the exposure to poverty. Does it have to do with where people live versus where they work or does it have more to do with their individual family situations than the neighborhood situations?

And then another question asks about the relationship between poverty and low-birth rate and other evidence of poor prenatal care. If you have normal birthweight, if you have good prenatal care, can that make up for the neighborhood poverty or does it not quite make up?

These are lots of questions. You can pick and choose which ones you might want to impact on. But the general theme is if we look beyond poverty or we look more in depth in a poverty, are there particular things that your data would suggest are specific risk factors or resilience factors in that context?

CYNTHIA ROGERS: This is a very robust discussion that we have as investigators in the group too. We have started off by looking poverty as this large construct that has lots of different factors. Most of the analyses that we have done, we did look at the individual factors that make it up to see if there were any kind of differences. We certainly know that particular factors load onto the disadvantage variable more strongly so the income-to-need variable. The family income loads very strongly and then the neighborhood adversity and parental education. That is kind of one way to answer that. We have been looking at individual. But the whole is greater than the sum of the parts. That is kind of one way to think about it.

I am trying to remember some of the other aspects of the question.

JOSHUA GORDON: Some of the aspects were are there things that might induce resilience to that poverty. You mentioned already individual family income and that can play a factor. What about working versus living in an impoverished environment? What about stresses if you are not in poverty, but you have significant work and life stresses?

CYNTHIA ROGERS: We looked at that psychosocial variable that included things like maternal depression and perceived stress and exposure to racism and discrimination and history of life events so ACEs and other traumas so that all loaded on our psychosocial variable.

And when we look at that in isolation, we will find a lot of the similar relationships. But as soon as we add social disadvantage, those relationships go away. That is one way to answer the question. Poverty seems to have more of an impact. Although you can also think about it in the pathway. That is something that we are also thinking about different ways of analyzing it.

But I will say one of the things that Dr. Lean did with the diffusion work was we took out those that were the most impoverished and then looked at the rest of the group. When we did that, we did find some relationships for psychosocial stress that were related to specifically diffusion in the cingulum. There very well may be some differential relationships when it comes to stress that we are able to tease out when poverty is not such a large factor in their life.

JOSHUA GORDON: Let me just ask and see if I got this right. I think what you are saying is that poverty is such an overwhelming risk factor that it is sort of swamps out the effects of other risk factors. But if you focus on the section of your sample that is less impoverished then you start seeing other factors that can make up a significant amount of risk. It is not like by removing poverty, we are going to get rid of everything. But by removing poverty, we are going to elevate everyone and then we start seeing the effects of these other risk factors --

CYNTHIA ROGERS: Right. Obviously, you can have stress from lots of different things. But the thing with poverty is it is not only stress. It is a whole host of other factors.

JOSHUA GORDON: We have just a couple of minutes left. With your permission, I might go over by a minute or two. If your answers go on, that is fine. I want to turn from risk to resiliency. There are a number of questions about resilience. You showed evidence of interventions that seemed to build resilience. What are the important resiliency factors that we need to think of here particularly let us stick with the impoverished communities that are really bearing the brunt of risk?

CYNTHIA ROGERS: One of the things that we certainly focus on a lot is the caregiver and the quality of the caregiving relationship and how that can mitigate some of the impacts of poverty. It is challenging though for the caregiver because if you are in an impoverished situation, you are under a lot of stress all the time. You might be working a lot in order to make ends meet. It can be challenging to optimally parent the way you would like. But we really do think that that is one way that resilience can be built. Education of the parent can also impact resilience factors. I think a lot more work needs to be done looking at the individual child to see if there are certain individual resilient factors of the child themselves too that can make them resilient.

But I think most of the bang for our buck is going to really be if we are not able to change anything external like say we cannot lift them out of poverty. We cannot improve their score whatever. It is really the quality of the caregiving relationship that can be I think the biggest buffer.

JOSHUA GORDON: That is really a wonderful thing to focus on and it is really helpful for us to think about. If we can alleviate poverty, we are going to have big impacts. If we can enhance the quality of caregiving relationships and I think that is consistent with a lot of other data really across the lifespan of our children, the better we can care for them, the better we can do for them.

I want to again thank you for the talk and just echo, first of all, echo the tens of comments put in the Q&A box saying what a wonderful presentation it was and thanking you for giving it.

I also want to recognize that there were a lot more questions that were given than we can answer. I tried to group them together so everyone got a little bit of a sense that their question was answered. I just want to recognize that it was a lot more demand than we could satisfy. We had well over 500 attendees at this webinar, which speaks to the tremendous interest in the topic.

Thank you so much, Dr. Rogers, for joining us. Thank you, everyone, from NIMH and from the extended community for joining us today. Thank you to our ASL interpreters who have been helping those who need them today. Again, you can tell your colleagues, friends, and family that this will be on the NIMH website for viewing within a couple of weeks. Bye-bye for now.