Tamar Gur, MD, PhD: Hello, my name is Tamar Gur, and I'm an assistant professor here at Ohio State University in the Wexner Medical Center, and an assistant professor in psychiatry and neuroscience. And I'm really looking forward to speaking to you today a little bit about my work and my interests, and really answer the question of how a psychiatrist and a neuroscientist ends up studying gametes. [Text on sceen: How does a Psychiatrist (and Neuroscientist) end up studying gametes? Tamar Gur, MD, PhD Assistant Professor Psychiatry, Neuroscience, 11/15/13] So, first, a little bit of background: Psychiatric illnesses are developmental, and more and more, we're thinking of not just the ones that occur in early childhood as being developmental, but really all of the illnesses that we see throughout adulthood have been shown to have developmental origins. Indeed, exposure to adversity during development has been shown time and again to be a risk factor for diseases such as schizophrenia, depression, and anxiety.And what I really became interested in during the course of my training was whether or not events that happen in utero, so while a mother is pregnant with her child, can affect the development of these illnesses, and really, whether, even before conception, even before pregnancy, whether stress and exposure to medications or toxins can contribute to long-term changes that we see in mental illness. [Text on screen: Background -psychiatric illnesses are developmental -Exposure to adversity during development is a risk factor for schizophrenia, depression, anxiety -Do events that happen in utero, or even before, contribute to long term behavioral changes?] So there's actually a lot of examples already seen from the clinical literature. So, antenatal stress and anxiety have been shown to contribute to increased anxiety and altered stress response in children, and this can be from things as varying as just daily hassles. So, going to work and things like that, as well as proximity to things like the World Trade Center during 911. In addition to stress, things such as inflammation and infection have been shown to contribute to mental illness. So, influenza infection during the first trimester of pregnancy has been demonstrated time and again to be associated with the development of schizophrenia during adulthood. [Text on screen: Examples -Antenatal stress and anxiety contribute to increased anxiety and altered stress response in children -Daily Hassles to proximity to the World Trade Center attack -Influenza (H1N1) infection during the first trimester of pregnancy has been associated with schizophrenia.] So I see a lot of patients and pregnant women are very concerned about not only their own health, but the health of their infant. And it became really obvious to me that there's a clinically relevant question to be answered when a patient comes to me with depression or anxiety or other mental illness: whether or not treating that disease with medication is something that will benefit their health, and what the outcome will be on their child is just as equally concerning to the mother, often. [Text on screen: Clinically Relevant Question] [Image on screen: White and black photograph of a pregnant stomach, with the person's hands resting below it. Several red-and-white capsules or ills are placed on the surface of the stomach.] So it became apparent that this was a very clinically relevant question that really could be approached both clinically but with basic research. So why is this important? Why is there even a question? Well, it turns out that depression itself is bad. It's been associated with preeclampsia, which is a very negative outcome during pregnancy, intrauterine growth restriction, premature delivery, which on its own is associated with a host of problems, developmental and neurobehavioral problems, neonatal complications, and compromised fetal placental function, which can also affect the developing infant. Now, the scientific literature does not support an association between maternal selective serotonin reuptake inhibitors as a class and major congenital malformations. [Text on screen: Why is this important? -Depression itself is bad: associated with pre-eclampsia, IUGR, premature delivery, neonatal complications, and compromised fetoplacental function -Literature does not support an association between maternal SSRIs as a class and major congenital malformations In bolded text for emphasis: However- is developmental exposure to SSRI causing behavioral changes?] But really, the question remains to be answered whether exposure to these medications during pregnancy does affect behavioral changes in the developing central nervous system. So, how do you figure out how a mouse is feeling? Well, I wish it was as easy as laying them on a couch and asking them questions, but what we do in my lab is preclinical studies in an attempt to figure out how a mouse is feeling. [Text on screen: How do you figure out how a mouse is feeling?] [Image on screen: Two clay mice are depicted in a therapy session—one as a therapist, the other lying on a couch.] So what you see here is an elevated zero maze, which is a measure of anxiety. [Text on screen: Preclinical Studies] [Image on screen: A top-down view of an elevated zero maze.] So you see, this guy is out here on the open arm, he's not feeling particularly anxious. He's feeling kind of brave and is able to go out in the open arm. A more anxious mice will spend more time here in the closed arm. Here's another paradigm we use, this is a forced swim test, which has been shown to model human depression. [Image on screen: A mouse is shown suspended in water inside a transparent cylinder.] And finally, down here, we have a social interaction paradigm where I can actually measure a mouse's inclination to be social and spend time poking its little nose through the hole with another mouse. [Image on screen: A series of images showing mice in various social interaction settings.] And these are preclinical ways, or a way to look in rodents at models of human behavior, so, anxiety, depression, and autism spectrum disorders. So what I'm interested in answering is this question of whether or not prenatal exposure to stress really does affect. You can see a little lightning bolt here in the parent generation, whether or not this is a way of carrying disease onward to the next generation. So, the transgenerational contribution of parental experience to illness in the offspring, and one very possible way that this is being potentiated is through epigenetic regulation. [Image on screen A series of graphic images that symbolize the ability of antidepressants to shield the body's reproductive system from stress-induced changes that could otherwise be passed onto the next generation. The word depressino is placed on an umbrella with a cloud labeled stress above it.] So not only do we get genes from our parents, but the way our genes are regulated can also be passed on through our parents. And now, studies are showing that stress actually in the father, which is what this image is illustrating, can be passed on to behavioral changes in this child through epigenetic changes. And the question I'm interested in answering is whether or not antidepressants here are really providing an umbrella from this, or whether they're having their own contribution as well. So, a series of experiments that I have underway are what you see illustrated here are an oocyte from a human and sperm. [Text on screen: Experimental Timeline] [Graph on screen: A timeline of an experiment designed to show how stress and antidepressant treatment before conception affect the offspring. Listed are the preconception phase, gametes, rest period, and behavioral testing] [Image on screen: 1. A magnified image of an oocyte 2. A sperm cell under a microscope 3. An elevated zero maze] And what I'm interested in doing is looking at the effect of stress and or antidepressant treatment on these gametes and epigenetic changes in these gametes. And then going ahead and looking at the effects of stress and antidepressant treatments on these same gametes, as well as the brains and the behavior in these offspring. So, I have to say, gamete retrieval is just a wonderful lab technique. And basically, what I have here is just a little petri dish with the ovaries that I've dissected out, and then you basically retrieve the gametes with this very thin pipette-man, and it's a time-consuming, but a very rewarding lab procedure. [Text on screen: Gamete retrieval] [Image on screen: 1. A small glass dish under a microscope. The dish contains a purple liquid 2. A person's hand holding a thin glass pipette, preparing to transfer or examine the biological samples under the microscope. In the background are the lab tools and dishes. 3. A highly magnified black-and-white photo shows a single oocyte under a microscope.] So, in summary, my research interests do include the effect of maternal psychotropics and stress on gametes, brain, and behavior, and the offspring, using the experimental paradigm I just showed you. I'm also interested in moving into translational research in conjunction with my colleagues in OBGYN and with Jeffrey Newport here, who's the director of Women's Behavioral Health. I'm going to be examining cord blood and placentas from both infants and mothers with mental illness and psychotropic exposure. So, that will hopefully, looking at epigenetic changes and other molecular changes, hopefully, that will provide us with a clue for the etiology of the transmission of disease from generation to generation. And also, I'm gonna be examining the effects of medication use in pregnancy on pregnancy outcomes themselves and see whether or not that mediates any changes in both pregnancy and neonatal outcomes. [Text on screen: Research Interests -Effect of maternal psychotropics and stress on gametes, brain, and behavior in the offspring -Examining cord blood and placentas from infants and mothers with mental illness and psychotropic exposure -Examining the effects of medication use in pregnancy on pregnancy outcomes and infants.] Thank you so much today for your time and attention.