Biology of Trauma: Dr. Tracy Bale on Epigenetics, Mental Health, and the Maternal Imprint

Transcript auto-generated from the episode audio; formatting has been cleaned up, but wording is verbatim.

Hi, I'm Cynthia Marks, and I head up the Holistic Psychoanalysis Foundation, founded by my late husband, Doctor Bernard Bail. Welcome to and now Love. Today we are exploring a profound and often unsettling question how much of our emotional life truly belongs to us, and how much is shadow written into our biology? Before we were even born? In the world of psychoanalysis. Doctor Bale spoke of the mother's imprint, the idea that a mother's unresolved trauma and her deepest unconscious feelings are projected onto the fetus, creating a psychological blueprint that dictates a child's destiny for a long time.

This was seen as purely symbolic or psychological, but my guest today is proving that these imprints have a physical home. Doctor Tracy Bale, no relation to Doctor Bernard Bail is a world renowned neuroscientist whose work on the biology of stress and inter-generational epigenetic programing shows us exactly how the environment of the womb and the emotional state of the mother chemically reshapes the developing biological set points. Welcome. Thank you so much for being here today. No thank you. It's fantastic to be here and I'm excited to talk about the biology behind trauma.

Great. We really appreciate that. And we love that we're making this connection. So how do you describe what you study and why should we be paying attention to it. And why does it matter? Well, it's a big question. I study, in one word, stress. And you can map that on to trauma as well. And I and I, my career has really been spent trying to understand the developing brain from many different angles for, broadly across neuropsychiatric disease. So everything from neurodevelopmental disorders such as ADHD and autism to all the way to depression and anxiety, etc..

Understanding who is at risk, why some individuals in the same family experiencing the same life basically are at greater risk than others. What is the biology behind that has been most of my career, and early on, in trying to understand how the brain develops, it occurred to me that there's influences that begin far before we thought and that, initially led to studies early in my career on on effects in pregnancy that we'll talk about today, but also even preconception even before conception happens a lot about mom and dad's experiences. Their trauma can biologically be transmitted at conception.

And so why is it important? I think if you look at the statistics right now for the levels of mental health disorders, just in the US, much less around the world, you'll see that they're at record levels. And part of that is the lasting effects of the pandemic, which was very traumatizing for many and continues to be an issue, but also just the current day stressors that are happening in this country have really pushed people, especially our youngest. So teenagers, young adults are presenting with levels we've never seen before for anxiety and depression.

And thinking again, what is the biology that that we need to understand and can we develop better treatments and better prevention? So but you were working on this well before the pandemic. Well before the. Pandemic, but you've just seen this sort of explosion since then. That would be a good term. Cynthia is explosion. It really has escalated. I think the levels at the CDC reported in the last several years were still that the record levels that happened during the pandemic, when we were all very stressed, you know, somewhere of the 70 to 80% of adults in the U.S. had some level of anxiety or depression symptoms that we've only really come down to somewhere in the 60 percentile.

And if you look at young adults being currently diagnosed and treated for for mental health disorders, anxiety, depression, it's somewhere between 60 and 70% in many communities. And again, that has a lot to do with access. So we may be underestimating. Yeah. What would you say that percentage might have been ten years ago or 15 years ago? Yeah. I think if you look at the the records by the CDC, we were somewhere in the 30s, 33%. So it's really is more than doubled right now. And I think the other thing that is very clear in this country is we don't have access to the health care.

So that ends up with people not getting the treatment that they need. And I think it's also troublesome that in and oftentimes in psychiatry, the medications that we're using are not as effective as we would like them to be. And so we're running sort of short of being able to meet people's needs even when they do are able to seek help. Yes. And and for me, just the idea of medication alone, I think a lot of times it's very valuable, the medication. But it's if we're talking about trauma and generational trauma, it's kind of a Band-Aid to just, you know, it could get you through the day.

Yes, that's exactly right. People are not being able to live to the quality of life that that they should be. I think oftentimes medication, the idea is that it gets you to a point where now something like therapy could be more effective. And if you can't access that therapy, but you're just taking the medication, it's very limited in in how your day to day life and the quality of your life, for sure, and for young people making decisions about next steps or careers or family, etc., is it's very worrisome. It is. And then, given the circumstances we have today for young people to sort of look forward, it's tough.

It's very tough. We're seeing this I speak as a scientist in my career. This is the first generation of young trainees coming through who are uncertain that they want to commit to training and going forward in science. And I think, again, also with the combine issues that are happening right now with targeting a lot of of the biomedical enterprise, including the national Institutes of Health and funding, that we're going to lose a generation of science and research, and it's going to be devastating to the to the health of this country. Yeah, treacherous, treacherous.

And it's, happening so fast. It's happening so fast, and it's very stressful every day. It's very stressful. I would say personally, it's very stressful every day. So when you began to think about this connection between trauma and, you know, the physicality of that, let's say, what got you there? What what what led you to think about the biology? Yeah, that's a great question, Cynthia. You know, I'm I am a scientist because this is how my brain has always worked. Like, I can't imagine doing any other job because science really taps into the who is the question here?

What is what's what's the underlying causality of how an individual processes the world and how someone might choose to find a healthy coping strategy versus somebody else who chooses an unhealthy coping strategy that leads them down a very dark spiral. I've always been intrigued by the brain. I mean, who isn't intrigued by the brain? It is such a mystery of how our brains biologically function. And so from a very early point in my career thinking, I think a lot of, psychiatry biologically spends time thinking about the brain as, as a box. We have this brain, and you are right now here and is focused a lot on identifying whether it's drug targets or therapies based on you right here.

But to me, it seems so obvious that you didn't start right here. You started way back when, when fertilization happened. And how the environment there's a there's a, a theory from David Barker, who has passed away some years now, but as a scientist about the fit. So you have your genetics that you had inherit from mom and dad and you did nothing you can do about those genetics. And they are really the major source of biology for your disease risk. So I will say, if you look at your family and your family has a lot of hypertension, diabetes, obesity, those are probably your genetics sets that you are at risk for.

And being aware of that can be very helpful. You can tailor your exercise or your diet and make sure you get health care that you need in the way that makes you less risk for a heart attack or stroke, etc.. If your family has a lot of cancers, that's also in your genetics. What we know a lot less about is when your family has a lot of mental health disorders. We understand a lot less about those genes, but those are your genetics. It's important to understand them. But if it's hypertension or it's cancer, we have screening strategies, we have medications.

If it's mental health disorders, we don't have a lot. And that is something I hope we have a time to talk to talk about today because it is something so important. And there's also a bias. It is very much a bias. There is a huge stigma, that makes mental health treatment and, diagnoses, so difficult in this country. Our health insurance and the, and the payments that physicians who are psychiatrists receive versus if you are a, general practitioner or in some specialty cancer treatment, for instance, what they receive from insurance is so much different than and so it makes it very difficult for how we think about improving health care in this mental health space.

Yes. And I, I see that in that cancer is almost a tangible thing. There's the science I see here on this little under this microscope. I see all these things. But that isn't so clear to most of us when it comes to mental health. And and even with what we're sharing, what the importance of trauma and how it affects your life and how it affects you physically, you know, is sort of, awkward. I think a lot of us don't you can't easily make what we're talking about tangible until we talk to you. Well, so there's like 100 things we could talk about in that sentence that you just said, Cynthia.

But one of the. So so let's talk about biomarkers. Yes. So so first of all, just to follow up on the stigma piece of it that is very much in this country, a stigma about, well, you've experienced trauma, you've experienced, you know, some events, etc., in your life, but if you were strong enough, you would just get over it. And that is very much a bias that makes seeking treatment and understanding your risk very complicated. And that is, I think, part of the lack of reimbursement in the mental health space is that if you're just tough enough, you can overcome it.

And that applies to men and women. It is very much to men and women and and how we think about understanding ourselves and, and how to give ourselves peace and space to accept that it is a biological experience, that you can't just wish away, that if you were just stronger and overcome it. Now returning to the biomarker question, which is something I'm enormously passionate about right now, and it occurred to me in the last several years, I just recently moved to the University of Colorado. I was recruited there as part of the psychiatry department.

And it occurred to me at this more senior stage of my career than in academia, as researchers, we are trained from the very beginning. When you start graduate school, that your goals are papers and grants, papers and grants. You need papers to get grants and grants. To get papers, you need to train the next generation. But it's papers and grants. And at some point in the last several years, having, personally dealing with family members and mental health disorders and really struggling with why is this the limitations of options, effective options, I thought, you know, papers and grants are important training the next generation.

Very important. But I want to have impact. I want to know that I I'm very passionate about my job, but I work very long hours and I work very hard. And because I love it, but I want to I want to know that all of that effort, that I left something at the end of my career that was impactful, that changed how we approach mental health in this country. And one of the things that we lack in psychiatry is biomarkers. And what I mean by that is if you have diabetes, they can do a test and they can tell you all kinds of things. They can look at your A1, C levels, they can look at your glucose.

If you have cancer, all kinds of of markers they can look for and tests they can run almost all other diseases, heart disease. They can do a test oftentimes a blood test. And they can give you a diagnosis and figure out a treatment strategy. We're very good at that. In psychiatry we have exactly none. There is nothing that we can do to accurately diagnose somebody predictively treat somebody and certainly not prevent. So, there has been many attempts at approaching this from different angles, often related to stress and trauma, but nothing has proven to be consistent and nothing has been implemented.

And so I'm working in this space biologically now that are, taking from blood what are called extracellular vesicles. And these are just small little nanoparticles that are secreted from every tissue in your body, including your brain, that communicate. Their job is to travel in concentration, very high concentrations to communicate between cells and between tissues, to talk about your current environment. And are they all, equipped to hand out the same message? No. That is what is so fascinating about these things. So the field of extracellular vesicle biology has made incredible advances in the last decade or two, mostly in the field of cancer.

And you can imagine if a tumor or a type of cancer is secreting you can there's ways you could detect them in circulation. So you can say, well, Cynthia, we're going to take a blood sample and we can look for this, this marker of the cancer that you had, and we can see if it's returned. We can see the concentrations of how it might be communicating with your immune system, etc.. So applying that now to psychiatry and how our body is currently communicating, trying to keep it healthy, a huge part of these nanoparticles is about the immune system.

And if your immune system isn't healthy, none of you is healthy. And I think we've for too long forgotten that the body is very important for the brain, for sure. Oftentimes I will joke with my neuroscience colleagues that they need to step outside of the box of the brain and think about the rest of the body. So we are currently, in my lab spending a lot of effort really trying to push forward in this space of biomarkers that we could actually, if we, you know, receive enough funding because it's a very expensive thing to do. One of the assessments you have to do is looking at is collecting these.

So for instance, we have a trial where it's treatment resistant, depressed patients undergoing a clinical trial for any number of anti-depressants that are new on the market. So whether it's psychedelic treatment etc., we can get samples before you undergo treatment and after. And now we can predictively model response from non-response. And that way we can really begin to say these individuals start differently and they end differently from controls. Does this give us new ideas about what we might be looking at for, for treating things like depression or anxiety or, you know, etc. all around, oftentimes very traumatized individuals.

So do you then in order to kind of get to this, the biomarkers that you're talking about, do you need to spend time almost, say, developing a template or a palette? Here are all the biomarkers we're looking for. Exactly. Right. Cynthia, do you have a background about that? In order to really understand, it becomes a lot of, a I and by computational modeling that we do, we say, okay, we apply this very stressful situation to a very healthy cohort. So we've excluded everything. There are no medications and I live in Colorado, so it's very easy to identify a very athletic, healthy cohort.

And we say okay now what do these biomarkers look like when they're experiencing stress. What should change. And that's the the base of this I think of is like the foundation of this biomarker house. And next we start applying this same stress paradigm to individuals from different traumatized groups. So we have cohorts actually around the world that we're looking at. So we have individuals from who have experienced different types of trauma. We have a prospective cohort, colleague of mine has in Detroit where their moms were recruited in pregnancy.

And the kids have been followed now for 35 years, which is super powerful because most studies are retrospective. Did you experience this? Did you experience that? And we all know that our brains can play tricks on us with what we've experienced sometimes for as a coping strategy to right, I don't want to think about those things. So this is a prospective. So they were brought in these kids throughout their entire lives for 35 years, and they've documented all the things that they've been exposed to and experienced growing up in Detroit. And that way we can prospectively look now at, okay, individuals who experience certain types of trauma.

So we've done studies on sexual trauma. We've done studies on neglect and abuse and try to understand does the timing matter. And that means we actually have studies from our biomarkers that experiencing certain types of trauma, such as sexual trauma during adolescence, produces a very different mark on your DNA than if you experience that type of trauma in childhood. Both of them very negative experiences, obviously, but but very different timing for how you are growing, maturing and developing. So it's not just your brain, it's also your body.

And through those studies, we are actually able one to identify a really unique sensory cell type in your skin. It's called a merkel cell, which I had never heard of until we did these studies. That is responsive. It's a light touch cell. So these women who had experienced this type of trauma only in adolescence, when these cells were really finally maturing, showed this marker in their blood. And we were able to trace that back to that experience. And when you look at where these cells are, it kind of makes sense that something like a sexual traumatic experience, these cells are in your fingers and your fingertips.

They're in your lips and they're in your genitals and in some places on your back. And so it sort of starts to come together. So now we're actually going forward now with, with a grant that we have from the NIH that will allow us to start asking more specific questions in and eventually, Cynthia, could we integrate that into PTSD treatment? So could there be a sensory treatment that that is able to undo that wiring, that programing that you mentioned earlier, that happens in those cells to reduce your body's response to constantly the vigilance that people with PTSD have.

So for a woman in that situation where there's been sexual abuse when she was an adolescent, and there are biomarkers now that that show that or represent that, what does she have to be watching out for in terms of health? And how likely is she to be able to undo that? Yeah, those are great questions and certainly a lot more research to be done, to understand from our studies. So we have a group, though those studies were initially done in inner city Atlanta as part of what's called the Grady Trauma Project, we're now validating them in this cohort that I mentioned in Detroit.

And what seems to be the case, the study we did in Atlanta was just women. The study we're doing in Detroit now is men and women, as I said, that have been followed for 35 years. And we're looking at the childhood comparison to the adolescent comparison. So the timing specificity is really interesting that the childhood version of that trauma presents more as is faster aging. And so we look at all these markers that indicate the rate of your cellular aging and hypertension, diabetes and obesity risk, whereas that trauma experienced adolescent seems to be more in the mental health disorders.

So a lot of those women with PTSD risk. And so that timing, it probably has a lot to do with the biology of what your body is doing at the time. You have that experience and what cells in your body are currently being programed. And so I, I think there's a lot in terms of what would you do or be on the lookout for. I think that our understanding of if something happens during gestation, which is a lot of the science that we're talking about today, that's a lot of that work has been done neurodevelopmental, because your brain is so quickly developing that the timing of when you experience something or obviously in pregnancy, your mom experiences some traumatic event, or is in a world where there's trauma going on.

So everybody's experiencing it's not something unique, but something that's happening in an environment. It goes back to that marker hypothesis of what happens as you're developing your body evolutionarily is trying to compensate to best fit you for the world that expects you're going to be living in. And what does that mean? That's a very big phrase, but it really means that at the level of your cells, your cells want to have to be able to function. So that as a species you survive and reproduce, etc.. And so I think this is a lot of programing that happens.

But when it presents, if there's a if there's a mismatch, sorry. So if there's a mismatch between the in utero experience and then the world you're born into. And the best examples of that are dietary. So your mom is overweight or diabetic. And so those signals that the baby is receiving are that this is a very calorically dense environment. It tells your cells you're about to be born into this space. You should be utilizing the energy sources differently, as if the the need for calories, which is the biggest stressor. I will just tell you evolutionarily that there is because a species cannot survive if you do not have enough calories.

So the mismatch is is oftentimes you are programed during gestation in anticipation of that world. And I think Cynthia, this goes back to Bernard's work of what mom is experiencing or what she has even experienced before pregnancy can biologically be signaled to the developing fetus and anticipation of that expected world you will be living in. So this is well before it's preconception, preconception. Preconception. Mom and dad, we do a lot of work in the space, also of dad. So one of the reasons we do that is because it's way easier biologically to get a specimen from dad than it is obviously from mom to ask questions about the environment.

But we absolutely do see that adversity in both mom and dad preconception effects. Those germ cells that come together than at conception. And we're always talking about the mother because the mother is responsible for bringing this baby into the world carrying this baby. But it could be that there is a completely, healthy mom physically, emotionally, with a dad who is is not. And that then will be transferred to this. That's exactly right. And you can imagine, I mean, evolutionarily, in order for I always think about this and for, for you and I, Cynthia, to be sitting here today means that every person in our family before us survived.

Every person that led to our birth survived. So there is some level of resilience that is built into all of us that are here today. But that doesn't mean that the environment can't then influence that. Right? And so sometimes evolution pushes us in directions that may not be, for instance, for mental health, our best fit. And I think that's something to biologically unpack for sure. And to go back to the woman who's carrying a child and she has she's obese. And now this child is delivered into the world. Are the cells within that newborn saying, we're expecting you to go into this world and have the same sort of, back and forth that you had in the womb.

And then there you are. And you're not having that. That's exactly right. And it tells a lot to your cells about, the program, the the energy source of every cell in your body, including your neurons and your brain is your mitochondria. And so, believe it or not, there's a lot of signals throughout your development that are important to, to program those mitochondria of how they're going, how every cell in your body is going to use energy. Do we need to store the cells that store calories? Do they need to be storing more because there's a risk of famine, right.

So that for a lot of us in this world, depending on, you know, where you come from, there's a lot of evolutionary programing that has come from fear of famine, right, because that is required for survival. And so unfortunately, we are in a calorically rich environment that we most of us live in. But yet evolution hasn't caught up with that yet. So it's still is pushing us. Oh, you have extra calories available. We should store them in case we need them. And that is sort of the risk of all of this information over generations. So if we're looking at someone who is really existing in a world of famine and carrying a child and then delivering that child, is that child, then preprogramed to be okay with famine.

That child is preprogramed to store every calorie it can find. And we often see that children who are born underweight, especially in those environments, we'll have this, what's called a rapid catch up, because their body will try to hang on to every calorie that it can. And then the danger of that is then, of course, having that, changes in your glucose processing, changes in your adiposity puts you at much greater risk down the road. And so right now in the US, we're seeing this huge surge of childhood diabetes. So then to that is there, is there some way when we when we finally.

Well, what I'd like to do is get to the place where we can say, I've got these mental health issues and I want to address them. And to be completely clear that that's a okay, I've got diabetes, and I want to address that. I'm more likely to have someone come to me with empathy when I say that. So yes, yes. So I feel like what you're doing, putting some biology to this, may get us to a place eventually where it is acceptable is. Absolutely a goal. And, you know, going back to the biomarkers I was talking about is that is absolutely a goal, because if your child has diabetes or cancer, you feel okay in discussing with your friends or family members or colleagues at work, maybe about this thing you're concerned about for your child.

But if your child is first episode schizophrenia or, showing all kinds of symptoms of depression or anxiety, we're less likely to discuss that because there is this idea that, well, then are you a bad parent or there's less understanding about these, the underlying biology. So yes, Cynthia, that's a that is a really big goal of identifying biomarkers because then it gives it that validity of this is not something I'm using air quotes here in your head that this is actually something biologically happening that should be addressed. Yes. And to allow parents to come to this in support of their children without stigma.

Yes. And to allow parents to figure out how to educate themselves when it comes to this. I mean, those are. Yes, I mean, early the earlier the intervention for any mental health disorder, the better. And so yes, having accurate ways to diagnose rather than I think I've heard many times, even from my family members of if you're just tougher on them, if you, you know, cowboy up. Let's that that somehow would which is, which is, I find so amusing because would you say that to somebody with, with diabetes or cancer? If you were just tougher, it would go away, right?

Yes. So it is so important. Yeah. It is so important for us to understand the biology so that we can give that that, validation. Yes. There is something that we can identify and, and the other side of that, or maybe the same side is, well, if we understand the biology better, can we can we design better interventions? It's interesting because we spoke recently with a wonderful woman. Her name is Mason Amick, and she I can say this out loud because she was on our podcast talking about it. She has a son who was diagnosed with bipolar one. She, you know, tried to get help for this young man and he struggled so seriously, struggled trying to get that help was, you know, like trying to walk up an ice mountain.

And she finally had to take it all into her own hands and create her own system to figure out how to get proper health care. And I mean, kudos to her. She's brought this forward without shame, without any. She doesn't care about anybody's judgment. She knows that this is something that all of us deserve to deal with in our own families, in our communities. And it was also interesting that her she asked her her families, you know, is there anyone in our history with some mental health issues? And the answer is no, no. And then it just sort of spilled out one day that, you know, aunt Sally had these serious mental health issues which would have been so valuable to her to know, but that we feel like I don't even know if we feel like it.

It's just sort of this innate thing that you keep under wraps. Yes it is. It is very true because again, it's seen as a weakness. And so crazy Aunt Shirley or whoever it is. Right. It is some weakness, something, something broken, but it's never seen as for instance, like cancer, where it is a biologically driven presentation of a disease or disorder that is not something that you manifested or that you're so weak you can't overcome it, but rather something we need to figure out a treatment for. And again, the earlier we can do that, the better.

And I, I applaud anybody coming on the show and talking about the difficulties in this space to navigate. And I feel enormously privileged. I have incredible access. I am in a psychiatry department, and I will say that I have a child who struggles and, I have taken him, I don't know, around the world, based on my privilege, because I have so many colleagues in this space to really look at what he is dealing with and try to provide insight. And I will say, even then, the toughest, toughest decisions and the toughest ways of not really not really being accurately diagnosed, until very recently, where he was finally diagnosed, accurately with having level one autism, which is a whole separate conversation, which is very different than level three, but nonetheless, the accuracy of our diagnosis is something that I am also incredibly passionate about, because it's too easy to look at somebody's presentation in the mental health space and say, depression.

But his depression with depression may be accurate, but it may not be the underlying right. If you have been misdiagnosed for 16 years and you had autism and it was never accurately defined, you may have developed depression, but that isn't the underlying issue. And I think too often it's easy, because physicians aren't given the time and the space to really spend time with, with the patient, especially in the mental health space. So you're, you're presenting with depression. We're just going to treat that depression, which. Doesn't really treat the underlying, you.

Know. Exactly. Right. So it's going back to your reference earlier to band aid. Is that oftentimes where we're giving band aids and those band aids really don't allow people to deal with or understand their, their foundation of what is the issue. Yeah. And isn't it amazing that you, with all of your act. Me with all of my access and privilege. Yes. It's been and I have many colleagues because I've been very open about my child's struggles. With my colleagues, I often have colleagues come to me now when their children are struggling to, to talk about their stories as a, as a I think people just need to feel like they can be heard.

But even in this space, Cynthia, people are hesitant to openly talk about their health or their child's health. ET cetera. ET which is again going back to this stigma because I'm surely it must mean something about my parents. Sure. Yeah. Or it's a reflection on my own mental health. That's also a scary aspect. But but that could be true for cancer as well, right? Is it your own risk? But I think we we have just this culture and it's it's not true in all countries. It is a very American thing to treat mental health as this side. It's interesting when you think about anybody who applies for a new job and they get hired and they're talking through their HR benefits, it's like, here's your insurance.

And on the side, here's your your mental health benefits, which is somehow different than your otherwise. Right. And this and this. Yes. Yes. That's very disappointing. And that is another piece of giving, providing the biology to the field may make a huge difference. I hope, if we can really push these biomarkers through and validate them, that we could change how we think about mental health disorders. So if you don't mind me using your son as an example, were you able then, through the course of all of this investigation to discover biomarkers?

No, we're not there yet. We're not there yet. We're so in the biomarker space that we're working in where we're focusing a lot on people who are already doing clinical trials for things like alcohol use disorder, treatment resistant depression trials that are already ongoing, where we can utilize blood samples being taken over the course of this trial. So it's really well, the study itself is very well designed, very well controlled. And that way the statistics will will bear out before we start applying it to really asking these much more complex questions.

And so I think that kind of takes us back to the trauma experience, which in, in the diagnosis of, you know, is it PTSD based. Is it depression anxiety you first have to go back to? Are there experiences. And so from for instance, the cohort of individuals in Detroit who are in their mid 30s is is such a valuable to the field. It's hundreds and hundreds of women that were recruited, but the moms are now in their 50s and 60s. The children are in their mid 30s and those children are also having children. So we have now in front of us three generations of well characterized experiences and exposures that we can start to ask these questions and bringing in and reexamining over three generations again, how if we give you an acute stress experience and take a blood sample before and after, can we identify here's how that healthy cohort responded.

Here's how you're responding. And that can tell us a lot about, you know, your immune system or your brain should respond like this in order to adapt to a stress. Do you already start? Which is often the case if you've experienced trauma that you're in this hyper vigilant state and so is your immune system, and so you're always on the alert. If you've experienced trauma often presenting as PTSD, post-traumatic stress disorder. And so we can ask these questions and again begin to see like, okay, so it turns out you need to be able to engage these systems in your body in response to those kinds of stressors.

And you're not. Now, maybe that gives us not only evidence that biologically something has different, but also then can we therapeutically maybe through medication, but also maybe through different types of therapy, work on engaging those systems so that your body isn't walking around in this constant vigilance state, because we know that it leads to faster aging and faster aging at the level of your cells is not a good thing. It's not just that you're looking more aged, which is, I think sometimes what people think about when I say faster aging, but it actually means your cells are wearing down faster.

And so your, your the longevity and durability of your cells is diminished. That's probably a pretty simple thing to look at as a. Sign, are lots of markers that science uses to look at. There's a thing called telomeres, which is sort of looking at the length within, of cells that they can easily collect from you without, you know, you collect them from your, your blood and ask the other biological signals that are saying, like, you, you're what this looks like is you're ten years older than you actually are. And I think that you can imagine if you're living in a community where there might be high levels of trauma due to lack of resources, lack of support, racism, discrimination, you name it, that you can imagine how that vigilance could wear down your body.

That I think is easy to conceptualize how that could happen. And then we we now understand a lot about the biology of why that is. So you have elevated stress hormones, right? You're just walking around in this high stress state. And what's interesting, Cynthia, is that when when you do studies, oftentimes you will bring in individuals and you'll ask them questions or they'll fill out responses. Individuals who are walking around in that very high stress state all the time often don't perceive day to day stressors the way somebody who is in a community where there's very, very low stress day to day.

And so therefore everything is sort of seen as as much more dramatic than it than it is that. So? It's also how we respond or don't respond can be also not healthy. And that is their experience. They don't know anything else. So living in this high awareness state, they don't think that it should be anything other than. That their body doesn't know differently. Right. But that high vigilance state always being aware. And I will say there is an evolutionary advantage of why that may happen. And you can imagine if you're living out on, the savanna and you need to be aware of predators like lions having a high vigilance state probably kept you alive.

And so evolutionarily, those genes and those mechanisms have survived because they kept us alive during different points in our evolution. But if you're yeah, if you're a ten year old sitting in a classroom trying to pay attention to a teacher and your genes and biology and experiences make you hyper vigilant, it's very difficult to pay attention to something like a didactic lecture from a teacher. When you're constantly aware of everybody who in the room is sniffling or coughing, what's going on outside the windows? Every your sensory system, which I want to say, going back to those merkel cells I mentioned earlier, but that's part of your sensory system is also on high alert.

Right? So you're you're feeling experiencing everything that's happening. And so, you know, for kids with, for instance, autism or many other neurodevelopmental disorders, schizophrenia. They like to ADHD. ADHD. Yeah. You often have these kids have identifiably at an early age very heightened sensory systems. So they're very sensitive to light sound touch the bumps in the socks. I mean, any parent out there who has a child like that, you know what I'm talking about. The I don't like the feel of the sand. I like the feel of my shoes. I don't want to touch Play-Doh.

I don't want to eat a lot of children, with autism, have eating issues because of the textures of foods or the fear of gagging, etc. and so these things, it's interesting with their biologically established that your sensory system is not filtering your brain from a very young age, isn't filtering out the things that many most people filter out they're very unaware of, like, oh, someone just walked in the room. I didn't even notice, or there's a change in the temperature or whatever. But individuals that for reasons of genetics by the environment that they experienced or their parents experience, we're understanding now have heightened that that alertness and that sensory experience that they're not able to filter it out and imagine, Cynthia, how exhausting that would be every day, that everything that's happening around you all the time is something you have to attend to, as opposed to.

Most of us walk through life not recognizing that, you know, our shoes are on the wrong foot, or there's some, yeah, whatever that that the energy and the, the attention of your brain to to attend to that. Yes. Exhausting. So, so you spoke about these three generations, so if, if my great grandmother had this horrible experience in war bombs going off around her, the she has my mother, my mother has me the way I present in terms of heightened awareness or depression or some sort of trauma, a lot of it is stemming from that. Absolutely. And so there's a lot of questions that come up of why are we seeing this as profound increase in diagnosis of autism is one example.

And I think there's lots of explanations there. It could be different experiences, but also we're just really much better understanding autism than we were 20 years ago. I would imagine that we didn't even think about it. I mean, I will say my child is 26, and when he was growing up, we just started. We had just started really understanding what we what we now think of as classic autism, which is now known as autism Level three. Before we really began defining this as a spectrum, the common feature across levels of autism is this social anxiety and inappropriate social attention.

And but level three is dramatically different otherwise from level one. Level one's considered like a high functioning, but they're very, very different. Symptoms are very different presentations. So we have grown in my child's lifetime of 26 years to really understand very much the difference between these and the president. So yes, so part of it is that but it's also I want to make sure it's very clear as, as a scientist that I make sure that we understand that huge piece of anybody's risk for any disorder cancer, diabetes or mental health disorders, autism, etc., is your genetics.

You first have to have the risk. And in many diseases, cancers, diabetes, hypertension. If anyone's done the 23 and me or any of those, you get those alerts and those are based off your genetic risk. It's not telling you you will develop. Diabetes is telling you you have an increased risk because we understand the genes, the sequences of those genes determine a lot about the level or the function of the gene when it's expressed, meaning DNA becomes RNA, RNA becomes protein if the sequence of which there can be variable sequences between myself and yourself, Cynthia, that the sequence determines the protein's function.

And so there might be a sequence that's really great function for that protein. And there might be a sequence that's not quite so great. And that might not matter unless you're in this environment that pushes your risk. So we call that the gene BI environment. And those two things are critical. We know especially in mental health disorders. To my knowledge, I don't think we have any gene sequences that are like, you will present with schizophrenia or you will present, but they are all risk. They're called risk alleles. And that just basically means we're starting to identify through genome wide association studies or Gwas, which genes in huge cohorts.

I think the largest ones are around schizophrenia. Understand some of the genes that are involved, but there's still only risk. And in cases, depending on which literature you look at, somewhere between 17 to 30 something percent of your risk may come from any number of these genes. So what's the rest? The rest is your environment. And your environment can be your experiences. They can be your mom's experiences. Your all of it becomes part of that rest of that, that GBG, that environment coming together at conception and transmitting signals again that are about my experience as a mom or dad's experience that tell biologically that developing embryo that becomes then a fetus that becomes then a baby.

Right? So those signals don't have to be perpetuated. It's not like, I call it's not the A to A to a to a, it can be the A to B to C to D, meaning. Cynthia, you had an experience, maybe in childhood that shaped a lot of the biology of your eggs. And before that conception, that, had a particular signal that biology of how that embryo after fertilization began to develop. Did it develop faster? Did it develop slower? How did it implant in the womb? How did the placenta begin to develop? And you can imagine if you use the analogy of the butterfly's wings, a slight change anywhere along there could make a big difference down the road.

And if that interacts, then with the DNA risk. There you go. So there's your totality of risk for any number of diseases. Unfortunately, we don't know enough about all of the the genes to understand all of the environments, but that's really where the field is right now, trying to understand can we identify the environmental that how much trauma do you need? Does it matter when that trauma happened? Can it be reversed? There's always a question that I get by some beneficial experience as well of course, of course. So the evidence is really strong that women who experience trauma during that adolescent pre-adolescent period, probably combined with the right genetics that we don't understand yet, are the highest risk for affective disorders, anxiety, depression across the lifespan, unless those women grow up in a very supportive, high resourced household.

So. Right. So there's always that there's so many factors along the way that could dial back a programing or dial it up. And so that's really, you know, one of the interesting things also Cynthia, that we can talk about is differences between males and females and risk, which is a huge area of trying to understand, you know, why do women presented such high levels with depression or anxiety after after adolescence? And why are neurodevelopmental disorders so male biased? And there's a lot of really fascinating biology behind those differences and risks for men and women all the way back, Cynthia, to the the point of conception that there are so many factors related to your chromosomes, your ex ex, if you're biologically female and XY if you're biologically male, that were just really beginning to understand of protection versus risk.

And as early as conception. So are there some simple things that you could point to in that difference? Well, one of the things that I am recently incredibly fascinated by in this field of trauma and stress is that there's a biological mechanism called X inactivation, which basically means that if you are a biological female, so X acts, every cell in your body has two X chromosomes. If you're biologically male, every cell in your body has an X and a Y chromosome, an order for the levels of all of the genes on your X chromosome to be similar between a male cell and a female cell, there's a process called X inactivation.

So all cells in a female biological female's body will have a random inactivation of one of the XS, and there's a fascinating way that this happens. And so it doesn't have to always be the same as it could be different X's. Right. Because you if you're biologically female, you get one X from mom and one X from dad. So it's randomized. Which one is inactivated. This process is crucial so that you don't have too much stuff. Expressed proteins off of X chromosome in female cells. However, this process does not happen until later in the embryo's development.

And so from the point of conception until you have what's called a blastocyst, which is later in development of that embryo, female cells x x have a lot more of these genes, which could be seen as being protective if there's something happening in the environment. And that's fascinating because so much we know of what may predict risk for autism or schizophrenia has been identified from the first trimester, and that is when this process is happening in embryo development. And so there's a lot to be unpacked here. But I think it's fascinating to think about what is the difference between a female embryo and a male embryo.

If mom has had lots of trauma or is experiencing an infection or lots of stress due to any number of events happening in this world, and does that change the risk for and again, as a neuroscientist, neurodevelopmental disorders and why we see so much of this presenting especially early onset schizophrenia and autism being so male biased? Is there something early on biologically that's protecting a female embryo? And then is it that later on the female becomes more susceptible? It is. The data show us that anything happening prenatally that we can point to.

So a biological experience, something happening at the level of the placenta that we can detect, placenta previa, any number of functions where there's a risk or some experience exposure of mom. So there's tons of studies that have looked at generational trauma and that in utero experience tends to put males at greater risk. Once babies are born, then it seems to shift to a greater female risk of somehow females have lost some level of protection. There's a ton of work, including out of out of my lab. That suggests that it may be something about a female placenta versus a male placenta, because right there, they're the ones that are.

The placental tissue is really that interface between mom and baby. And so somehow an x x cell based placenta versus an x y cell based placenta, because the placenta is actually derived out of the embryo. So it has a sex scene. And there are mechanism by tons of biological mechanisms that have been identified that seem to be different between an x x and an x y. That would suggest, responses that mom, as a mom has had trauma in her life. She will now maybe be hyper vigilant and having constant elevated levels of cortisol or elevated reactions in the environment being that vigilant.

And so that changes. It can shape her uterus. It can shape how how, nutrients are transported. It can shape the development of, how an embryo implants in the uterus. There's so many steps along this way that her life experience can be shaping how those those biological signals are happening. And so if a mom has had lots of trauma, but she's sought out therapy and it has resolved and developed, healthy coping strategies and ways of dealing with stress in her environment, maybe that then reverses those those signals and allows a healthier embryo implantation.

And and placenta. But we know a lot from things like the Dutch hunger winter, Swedish famines, Holocaust survivor studies that there's a lot of mechanisms being pre-conception that are biologically carried forward, and things like embryo development and the placentas function. So the idea is before we conceive, we do our very best to make ourselves as healthy as we can. Healthy as we can, giving ourselves the grace to recognize that we can't fix everything that we are not. Responsible. I think there's so much mom blame that happens out there and so much mom guilt that I want to make sure that we're not carrying on that message.

But or and that that seeking out, healthy coping therapy, yoga, whatever we have the space and the resources. That's not true for everybody to to deal with, but understanding and giving ourselves I think that that grace and forgiveness, I think, goes a long way to lessening the guilt. And again, no stigma, no judgment. But you're right. So many of us, we're just doing the best we can to put a little bit of food on the table. So to think about these other things is a luxury. And also that, as you've described it, there are so many little avenues that, have to be considered as your I mean, just biologically that by the time you deliver this child who could expect the entire scenario to be perfect.

I have to say that understanding everything from conception through all of fetal development, especially when thinking about the brain, I'm amazed every single day that babies are born. There's so many places where things that the the precision in mammalian development of how this gene has to turn on at exactly the right time and produce exactly enough protein in order to signal this thing. And if that doesn't happen, I mean, it's really is a remarkable process. And it is. Yeah. And that that does happen is it. Does happen now. It does happen.

And I also want to emphasize again, we you can't outrun your DNA. You are given this, this roadmap from from your parents who inherited it from their parents. We can't undo that roadmap. Your DNA is your DNA. And I think, as you mentioned earlier, epigenetics, Cynthia, and epigenetics, just for the listeners who may not know what epigenetics are, is your DNA sequence is set. You can't change your DNA sequence. But what lays on top of that DNA are these epigenetic marks. So there could be methylation or other types of modifications. They're called biochemical modifications.

Those are your epigenetics. And why those are important is that they those marks can be changed by the environment. Unlike your DNA sequence. But they're important for how genes get expressed. They can turn on and off genes they normally do. There's a whole process that's required for how genes get turned on and off. But there are other genes where they can be modified by the environment. And so, for instance, how methylation is a is a biochemical mark on DNA that often represses it turns off the expression of genes. And you need that, that's that's part of a normal, healthy cellular process.

But the environment sometimes your diet, other things can modify those marks, sometimes temporarily, sometimes for a lifetime. And they wear out. When we talked about the biological aging, those are some of the things that can wear out over time. And then can can change how a cell functions. And you want your cells to be happy and healthy and able to adapt when your glucose levels are high because you just ate, or when your stress is high because something's happening at work or in your home. You want your cells to say, okay, I, I see this happening, I'm going to adapt and respond.

And then we're going to go back to a baseline. That's a healthy way that doesn't happen for all of us. And as we age, that process becomes harder and harder for cells to do. They get worn out. If you are aging faster, that's going to lead to a wearing out of your cells and less ability of your cells to respond. So will there be a day where we can look at this information as we travel through life and say, hey, you know, I see you know, for your age, your cells, or they're looking a little older than they should. Let's figure that out. Why? What about you is making that happen?

And then you have a chance to go back and sort of think about your mental health? Gosh, I hope so. I hope so, Cynthia. And I hope that that by the biomarkers that my lab is working on, that we are able at some point to be able to take a blood test from everybody at some point in their mental health evaluation and say, yeah, we're seeing these markers, indications here. Now, we have a therapeutic approach to help you so that you don't continue on this path. And so maybe some of that is, a process of, of therapy, maybe a process of of healthier living, etc..

But we all know if you go into the doctor's office and they see markers of increased risk for diabetes or high cholesterol, we have medications for those. Now, we have ways for physicians to recommend to you. Here's the path that you're on. This is not good. If you would like to prevent heart disease or stroke, etc.. And we see it in your family history, this is that that genetic piece. Again, here are some suggestions. We can put you on this. We can put you on Lipitor. We can. There's all kinds of things that we can do. Part of it is your responsibility to say, okay, I'm gonna look at my diet.

I'm going to dial back and the alcohol. I'm going to dial back on saturated fats. Since we have so much great evidence to give recommendations to people to help them, my hope is that we can create that same path in the mental health space as well. So it could be that, there it's it's showing up that maybe there's this proclivity toward schizophrenia, let's say. And if you knew that, you could take that back and treat that in a mental health way so that you could sort of be aware of it and follow a path that steers you clear of that. Again, you're it's a lot of well, it's not a lot to ask, isn't it?

I think it's, you know, the difference. Again, for something like schizophrenia versus, breast cancer, I'm going to use this as the comparison there is that we have so many imaging techniques. It's a physical thing that we're looking for in addition to markers. We don't have that for schizophrenia. But what if we did? What if we had these nanoparticles that could tell us that this is likely progressing, toward a first episode psychotic break in schizophrenia? There are a lot of current known therapeutic interventions that you could hopefully work with.

But probably as we move forward in this biomarker understanding, just like for breast cancer, right? So 50 years ago the survival rate for breast cancer was way worse. And so improve now. So Tom Insel used to be the years ago, decades ago actually was the director of the National Institute of Mental Health at NIH. And when he gives talks now, he often has this slide that I love to show to people. That is, if you look at diabetes, heart disease and cancer in the last 50 years, the improvements with therapies, interventions, etc. and life span is amazing.

If you look at where mental health is, it's a flat line that is very, abysmal. If we could apply that same attention that we do, if you. So, for instance, if you get online and look at the National Institutes of Health, one of the things you can see is the funding of how we as Americans, largely through Congress, who decides the NIH budget? If you look at across all the institutes, mental health, drugs of abuse, alcohol, and then you look at cancer and, and you continue on down the institutes, you can see where our priorities are. Yes. Those things we've deemed socially.

Acceptable, we've made enormous advances in cancer and don't get me wrong, cancer research is incredibly important. We all know loved ones or family members or friends who have struggled. We've made incredible strides. Mental health, if you look at that, our image budget has not budged much and is, I don't know, something like a third or a half of what some of the other institutes are. It tells you where our priorities are. And I also say, if you look at the CDC numbers across the United States of America for dollars and dollars spent on, individuals who are not able to work or function because of mental health disorders, I'm also going to put out there that every time a school shooting happens, what do we blame?

Mental health? If we look at all of the lives impacted by mental health disorders, why have our priorities not shifted of where we're applying those research dollars? How are we going to make those strides? I will tell you, as an individual who is enormously passionate about identifying these biomarkers, I have the luxury currently because of my recruitment to the university. But those funds are they won't last forever. So labs who are really trying to identify the biology that we can address, generational trauma, the funding that we are able to to find for those studies is so limited and more limited now than ever with the current state.

But are there more individuals that are interested in this? Oh, yes. Yes. So the possibility of it becoming better funded years from now, let's say, exists. Hope. The hope. The hope is there. Synthetic hope is there. I just returned actually from a conference called the American College of Neuro Psychopharmacology, which is, a college that has the top of the top of researchers and clinicians who are interested in biological psychiatry to come together and discuss new clinical trials, to discuss new treatments, etc., across the mental health disorders space and the common theme that I hear again and again which which inspires me is we need biomarkers, we need biomarkers, we need biomarkers.

Because how you give the example of depression, everybody knows somebody who has or has experienced depression. Depression is such a wide diagnosis that you can imagine without even having a science background, that you put together a clinical trial for a new drug or a new therapy, and you recruit based on depression diagnosis that that the presentation, because it's such a wide area that is really hard to target and identify what this population would do better with this drug than this population. If you had a biomarker that could say, okay, here's what we're recruiting, because we know that our drug targets the immune system in this way, or targets the brain in this way.

We don't want everybody with depression. We want depression in this area to validate this drug. And we don't have that. And so what ends up happening is that we just show very little unfortunate, evidence for the longevity of many of these drugs because it's just so variable. Human beings are very messy. Yes. So everybody's getting the same drug. Yes, yes. And that's why anybody who's who has sought out treatment for things like depression is often try this. Let's add this. Let's take you off this one and add this one. And it's just trial and error.

It could go on for years. It could go on for years. And people during that time are not living the quality of life that that they deserve. But I also say people tend to beat themselves up when you try drug after drug after drug, and it's not helping you begin to tell yourself the story of how broken you are. And so if we had biomarkers that could predictively say, actually you have this set of markers, this is the drug that will best benefit you. We could get there a lot faster. And then that drug could potentially put an individual in a place where they could say, now I'm ready to look at.

Now I'm ready. Exactly the idea, as a neuroscientist, how we describe that experience, the is that the drugs can it's called plasticity of your brain. And they can open up that plasticity to allow good things like therapy to come in. Yeah. So you are more in a, in a zone where you can have a conversation more receptive. That's exactly right. Yeah. Are there findings from your research that surprised even you in how deeply interconnected mother and child are? Yes, there are findings, and this is one of the things that, you know, being an academic researcher, it's a pretty stressful career, especially if you're driven, you know, getting we live and die by our grants.

But the thing that keeps me doing this, besides training the next generation, which is so important, but it's also the discovery. I always tell my trainees when they're very stressed out, that it is one of the only careers I can think of where at some point, when you're doing your experiment and you're analyzing your results to be in the middle of the night, whatever it is, that for that moment, you are the only person in the world that knows that result. And that's pretty. Cool. Oh that's awesome. Cool makes all that grant writing. It makes all that grant writing worth worthwhile, for sure.

And the other part of that makes the grant writing worthwhile is the idea that you could, in that discovery process of writing the proposal. Not only is it to convince the your colleagues at study section to fund you, and I will say, right now we are at NIH at a 4% 440 4% funding. How do you even muster the excitement to write a proposal? And all weekend and on your vacations and writing, writing, writing, writing because you're passionate about making change. So the things that surprise me, honestly, are and that I really enjoy, I enjoy nothing more than a trainee coming into my office, you know, sometimes with a dripping piece of of literally a dripping film or a dripping blot or something to show me a result, that those are the best.

I can't tell you how many times I've. I personally still stay up late at night with a new set of data, because you just never know. What's that next thing that's going to make a difference. So for someone to come to you with something unique that you. Love it, love every minute of it and the things that surprise me, I think the thing that continues to surprise me is how different men and women are biologically, how we respond. We can get to the same end point through very different, right? So you can get to the same destination through very different paths and roads.

And I think evolutionarily, there's probably a really good reason for that. I think, you know, coming back to our main discussion point here is about mom and pregnancy. You know, mom is doing the heavy lifting here, right? She's gestating this child. And if it's a male fetus versus a female fetus, we know there's all kinds of evidence for differences of an interaction biologically with mom. But even like whoever thought that a placenta could have a sex right, and that it could respond very differently to mom, is developing diabetes, her mom has an infection, etc. and how that placenta doesn't have a think is there's no brain in the placenta.

So it's it's just biologically responding to mom's environment, trying to get everything it can for the developing fetus that that could have a sex specificity that for sure. I think that's brand new news to almost all of us. Interesting. Yeah. So I see a whole other podcast episode about this, about the difference between men and women and this placenta and, and even just studying some of what you've talked about, how how amazing this placenta is. It is the placenta is amazing. And but it also brings up another aspect that I want to make sure we, we address, which is women's health.

We had some really big pushes in the previous administration towards funding women's health research. And unfortunately, a lot of that's been walked back. I don't know if people are aware that if you look back through most clinical trial data for development of drugs, if you look at even basic research of how we use, for instance, different animal models, the predominant animal, and across most research, cancer or or neuroscience research is, is the mouse. That has a lot to do with that. We can manipulate the the genes to ask specific questions.

Almost all of those studies, are done in males, male cells, male mice, male humans, and that comes from this myth that has been debunked over and over again that females, because they have, an estrogen cycle and estrus cycle in rodents and a menstrual cycle in women that makes us messy and variable. I'm speaking in statistical terms. Difficult to study, difficult. To study, difficult to study. And, and some in the human, some related to clinical trials, etc. a lot of that is also the vulnerability because you could be pregnant. So I'm not going to say it's all, that.

But what that has led to is this huge amount of data that we draw conclusions from about heart health, brain health, bone health. Etc. skewed. Skewed based on the man and not on the woman. And so women's health research, Cynthia is hopefully we'll come back to this again. And there's so many entities around the world in the U.S, the society for Women's Health Research, I'm part of the the Luteum and Women's Research Center at Colorado, pushing for everything from clinical trials to medical care, evidence based understanding of the difference between how women and men, not how just how we process the world, but how our cells respond.

I've been often told by my, cardiovascular colleagues that if you open up the chest of a woman versus a man and blindly put your hand in, you feel a profound difference that women's hearts are squishier and softer. Than my. Gosh. And so there's just so many fundamental differences between men and women that we cannot uniformly apply the, the, the old data, how women process and metabolize drugs is often different than men. There's really classic examples out there of everything from anti-depressants to other types of medication that women metabolize them differently than men do.

And it's different in a woman pre menopause versus post menopause. And those could be very dangerous differences that we need to understand. And we don't. And we don't. And that I mean we must do this because it's the women who are bringing all of us into the world men and women. That's exactly. Right. And if we don't know enough about a woman's process, we can't be doing our best job. Hundred percent, 100%. I think there are some organizations that, around this rise in autism. We go back to that again that, suggest generations ago before we because, again, studies have been done in men and not in women, that they would give crazy medications to women in pregnancy to fight nausea.

This is crazy studies. If you look back in the 40s and 50s, what medications they were giving to pregnant women. And I think there's, somebody actually once sent me, sort of this advertising of, like, why you should take these drugs so that get over your nausea, get up and make your husband breakfast kind of of of guilt. Right. And here, let me light your cigaret. Yes. And so what those medications in pregnancy may have been doing. And, so if you think intergenerational, let's just talk about the biology. Mom ingests some medication during her her pregnancy.

The fetus is developing so you can have a direct impact on on that baby. Sure. Or not. So maybe that baby's born ten fingers. Ten toes. We don't really see a difference. However, the germ cells for that baby are also developing. That will give rise to the next generation. So there are some studies out there that are interested in understanding whether it's medications or things like trauma that could better understand the biology of when those signals can be stored. So maybe you don't see it in the, in the we call the the F1. The next generation, but in the F2 the grandchildren instead you're seeing these effects.

So we have we are incredibly lucky to have this amazing collaboration right now with the Dutch Hunger Winter, or known as the Dutch Famine years. And this was at the end, towards the end of World War two, when the, around Amsterdam and some other areas of the Netherlands, there was a blockade by the Nazis to cut off food supply. And so for, I think, the better part of a year, year and a half, these individuals were really limited in calories. I always use the equivalent of like, mocha Frappuccino from Starbucks for your whole caloric intake of your day, including pregnant women.

And so the the Dutch decided to to follow these individuals so they have cohorts that they have followed, they individuals that the exposed individuals are the individuals who were gestating. So they were the babies exposed during that famine period. So of course, it's very stressful. And traumatic and calorically challenging of their longevity and health. And they've been, like I said, studied for I think these individuals I mean, what is 42 to now, are mostly dead or dying and their health, many of them the significant effects where they died young.

And so, Audrey Hepburn is a is an example. She was exposed. She was actually not exposed in utero. I think she was a toddler and she was exposed. All kinds of health, including mental health disorders, are are predominant in these individuals. They've tracked things like schizophrenia, risk, depression, meta metabolic disorders, diabetes, etc. there's just a wealth of information. So throughout their adult lives of these individuals they've collected, they've done all kinds of studies cognitive, neurodegenerative developments, etc. but they also had blood samples.

And so to this question that we're interested in of identifying biomarkers, we have blood samples from these individuals that we're now, analyzing to see if we can overlay these data with individuals who presented with depression, anxiety, schizophrenia, etc.. Can we identify the biology of prediction? Yeah, I mean, what what we're really trying to do is to help people understand that our emotional well-being is of the utmost importance if we're going to heal ourselves and heal the world. So understanding and I think going back, Cynthia, to the thing that you said in the very beginning, which is the stigma of and the limitations on the biomedical research end of things all the way to how we conceptualize our own mental health.

And of course, there's self-responsibility, just like there is with any disease risk. But there is biology, there's the biology of of what we inherit from our parents genetically, but also preconception experiences. Very much is involved in our risk and presentation and therefore should be also understood biologically. Hopefully we can design better therapies and preventions. Yes. And that you are connecting these two worlds is again so exciting and fabulous. And I look forward to the day where all of these elements that we think about, you know, that.

How does the feeling of loneliness or or fear or. Action oh, Cynthia, post pandemic so hard to get people to socially interact again and it's going to have. Consequences. And what we're going through in our world today, in our communities, all of that is affecting us. Very is very stressful. And I, I too, I'm very passionate, very passionate at this point in my career that we do a better job of identifying all that we can for for biomarkers. So let's cross our fingers that we can get there. Well, I hope we can speak to you many, many times again in the future.

Thank you for helping us. Ground Doctor Bales psychoanalytic theories in the concrete reality of the lab. It is powerful to see that what he has described as the mother's imprint is actually a measurable biological narrative, one that affects everything from our immune systems to how we process stress. Your work reminds us that we are born with these set points. Understanding the biology is a major step toward reclaiming our own lives. Thank you again. It's just precious to talk with you. Thank you so much for inviting me, and I look forward to hearing follow up in the years to come of where we are with integrating these concepts.

And yes, me too. Same. Thank you.