Why do mental health professionals diagnose mental illness by medical observation and not by something more definitive like a blood test or a brain scan? It’s often pointed out that illnesses like cancer or diabetes have blood or urine tests, scans, and so forth. So why not mental health issues?
Join us as our host asks these questions and discusses the state of genomic research with the executive director of the National Institute of Mental Health, Dr. Joshua A. Gordon. Dr. Gordon shares current research, explains the limits of scientific testing, and answers why there isn’t a more definitive test for disorders like bipolar, depression, schizophrenia, and so on.
“Simplifying can be useful because it helps us understand fundamental concepts. Genes cause mental illness. That’s true, right? But it’s also not wholly accurate. It doesn’t tell the whole story. The whole story is genes contribute to mental illness, but so does trauma. So does infection in pregnancy. So does stress because you lost a job. All those different things contribute to mental illness. We have to be able to let some of that complexity. Because if all that we do is focus on genes, we’re going to be missing a big part of the story.” ~Dr. Joshua A. Gordon
Joshua A. Gordon, MD, PhD, is the Director of the National Institute of Mental Health (NIMH), the lead federal agency for research on mental disorders. He oversees an extensive research portfolio of basic and clinical research that seeks to transform the understanding and treatment of mental illnesses, paving the way for prevention, recovery, and cure.
Dr. Gordon pursued a combined MD-PhD degree at the University of California, San Francisco (UCSF). Upon completion of the dual degree program at UCSF, Dr. Gordon went to Columbia University for his psychiatry residency. He joined the Columbia faculty in 2004 as an assistant professor in the Department of Psychiatry.
Dr. Gordon’s research focuses on the analysis of neural activity in mice carrying mutations of relevance to psychiatric disease. His lab studied genetic models of these diseases from an integrative neuroscience perspective, focused on understanding how a given disease mutation leads to a behavioral phenotype across multiple levels of analysis. To this end, he employs a range of systems neuroscience techniques, including in vivo imaging, anesthetized and awake behavioral recordings, and optogenetics, which is the use of light to control neural activity. His research has direct relevance to schizophrenia, anxiety disorders, and depression.
In addition to his research, Dr. Gordon was an associate director of the Columbia University/New York State Psychiatric Institute Adult Psychiatry Residency Program, where he directed the neuroscience curriculum and administered research training programs for residents. Dr. Gordon also maintained a general psychiatric practice, caring for patients who suffer from the illnesses he studied in his lab at Columbia.
Dr. Gordon’s work has been recognized by several prestigious awards, including the Brain and Behavior Research Foundation – NARSAD Young Investigator Award, the Rising Star Award from the International Mental Health Research Organization, the A.E. Bennett Research Award from the Society of Biological Psychiatry, and the Daniel H. Efron Research Award from the American College of Neuropsychopharmacology.
Our host, Gabe Howard, is an award-winning writer and speaker who lives with bipolar disorder. He is the author of the popular book, “Mental Illness is an Asshole and other Observations,” available from Amazon; signed copies are also available directly from the author.
Gabe makes his home in the suburbs of Columbus, Ohio. He lives with his supportive wife, Kendall, and a Miniature Schnauzer dog that he never wanted, but now can’t imagine life without.
To book Gabe for your next event or learn more about him, please visit gabehoward.com.
Producer’s Note: Please be mindful that this transcript has been computer generated and therefore may contain inaccuracies and grammar errors. Thank you.
Announcer: You’re listening to Inside Mental Health: A Psych Central Podcast where experts share experiences and the latest thinking on mental health and psychology. Here’s your host, Gabe Howard.
Gabe Howard: Thanks for listening to the podcast, everyone. I’m your host, Gabe Howard. Calling in today, we have Joshua A. Gordon, MD, PhD. Dr. Gordon is the director of the National Institute of Mental Health, or NIMH, the leading federal agency for research on mental disorders. Dr. Gordon, welcome to the podcast.
Dr. Joshua A. Gordon: Thanks, Gabe. And you can call me Josh.
Gabe Howard: Oh, thank you so much, Josh. I really, really appreciate that. Now, today, the majority of our discussion is going to be about the NIMH’s research and focus on genomics. But before we get to that, I wanted to first ask that as of right now, if I understand correctly, there is no sort of medical test that will detect or confirm disorders like bipolar, major depression, schizophrenia. Currently, these things are diagnosed and treated based solely on a doctor’s observations. But I have to ask, why is that? Why isn’t there a blood test, or a urine test or some sort of scan for these disorders, for mental illness disorders? There are for cancer and diabetes.
Dr. Joshua A. Gordon: It’s a really good question, Gabe. The biggest reason is that unlike some of these other diseases, we don’t have a precise understanding of the fundamental biology that goes awry in mental illnesses. In diabetes, we know it’s about insulin. We know it’s about the pancreas. We can test blood sugar. In mental illness, while we have some really wonderful strong hints and we’re learning more and more, we don’t have that fundamental understanding at the same level. There’s a second reason, too, which is that these illnesses are heterogeneous, meaning that they are a little bit different in each of us. And so, we don’t know whether each of us has a different biological reason. Um, coupled with all the other things, the environmental factors and social factors or whether there is fundamentally something in common that we just haven’t figured out yet.
Gabe Howard: In recent years. Josh, the organization that you’re the executive director for, the National Institute of Mental Health, has increasingly focused on genomics. Now, to put it simply, for our listeners, genomics is the study of an organism’s genome, its genetic material, and how that information is applied. Does the fact that your organization is researching this show that you believe, or at least the National Institute of Mental Health believes that mental illness is genetically determined? I ask because I know there’s a lot of conversation about is mental illness nature or nurture? Is it environmental or are you born with it? Is it something that’s inside us, or is it something that happens to us? Does this research into genomics show that these questions have been answered, at least for the National Institute of Mental Health? That mental illness is definitely biological?
Dr. Joshua A. Gordon: The answer is yes and no, Gabe. Mental illness is absolutely biological, right? It exists because that’s the way our brains work, right? The brain creates behavior. The brain is a biological thing. Mental illness arises when the brain is functioning differently, and it causes challenges in our thoughts, in our emotions, and in our actions. So yes, it’s biological number one. Number two, it’s also all the other things that you think about with mental illness, stress and trauma and how you grew up and what you eat and whether you have a good immune system. All these other things also contribute to mental illness. So yes, it’s biological, but the brain doesn’t exist. In addition, isolated from the rest of the world, it exists in a complex environment. Then the second piece of your question, Gabe, was, is it is it determined by genetics there? I would say the answer is no. Genetics are incredibly important factors that influence your risk for mental illness, because it’s the genes that cause the brain to develop the way it is, and the genes that determine how the brain reacts to everything outside of the body, to your social situation, to trauma, to what happens in life. So, genetics contribute to the risk for mental illness. They contribute differently for different mental illnesses, but they absolutely contribute important portions of that risk. But they don’t act alone. Genes act in the context of these other factors. The reason why we prioritize genetic genomic studies is because they’re a clue that we can easily study that is very, very powerful. And that allows us then to ask, how do those genes affect how the brain reacts to everything else?
Gabe Howard: You know, along those same lines, I remember when I was diagnosed with bipolar disorder and I was put on drugs. You know, psychiatric medications. And I say randomly, I, I recognize that it’s not randomly a psychiatrist, you know, evaluated me, looked at me and made the best decisions with the information that they had at their disposal. But of course, what they didn’t know is how I would react to those medications. Would I have a sexual side effect? Would I gain weight? Would they even work? They just they just had to observe. This is this is how it was done. Now, years later, after I was stable with my bipolar medication regimen. So, I was doing really, really well. I was part of a clinical trial where they gave me a genetic test, and then they looked at that test to see what medications it recommended versus what medications I was on. Now, unfortunately, I do not know how those things lined up. But now this is in common practice. I talk to people who are diagnosed with schizophrenia, bipolar disorder, put on psychiatric medications, and one of the first things that they do is get a genetic test, and then they get those results back. And then the psychiatrist looks at psychiatrist, looks at them and says, I’m going to put you on this antipsychotic, or I’m going to put you on this antidepressant based on that genetic test. How does that work? Do you feel that that’s relevant science? There’s we don’t hear a lot about it on the layperson level. We just hear about people in our support groups who are like, well, yes, I was genetically tested and that’s how I got my meds.
Dr. Joshua A. Gordon: There isn’t really good evidence to support the use of these genetic tests in clinical practice today. The tests do make some modest predictions about your likelihood to get a side effect, or your likelihood to respond to the medicine. But those predictions are really kind of weak, and no one has shown that using these tests can get people better, faster, or avoid side effects. So, I do not think that there is sufficient data to use genetic tests to choose a treatment. That said, there are a lot of promising avenues for learning more about our patients that can help the patient and the doctor together to make a better decision about what treatment might work for them. For example, research funded by the National Institute of Mental Health has shown that taking an EEG or recording brainwaves from patients with depression can make a prediction about whether those patients are likely to respond to a serotonin reuptake inhibitor. Compared to other forms of treatment for depression, like cognitive behavioral therapy. If we can really nail that down and demonstrate unequivocally that that simple test of the EEG can help predict whether you’re going to respond better to one treatment than another, then we can put that into practice and use it to guide decision making. And we are almost there with some of these other tests besides genomics at this time. And what we hope is that in the end, we can combine different pieces of information about our patients, their genetic makeup, their brainwaves, maybe a blood test, maybe some behavioral tests, and make quantitative predictions about how likely you are to get a particular side effect or to respond to a particular medication so that the doctor and the patient can use that information to decide which thing to try first. Those studies are ongoing right now, and we think that within 5 or 10 years, some of these things will be useful in the real world.
Gabe Howard: You mentioned cancer, and I’m constantly comparing mental health to physical health. And one of the things that they have over in physical health is something called precision medicine. Do you think we’ll ever see precision medicine over on the mental health side?
Dr. Joshua A. Gordon: We already have one example of precision medicine. So, I would say the answer is definitively yes. So, what do I mean by that? Well, as you know, there are many different treatments for depression, right, Gabe? You can have psychotherapy. You can have, uh, you can have all kinds of different drugs that work through different ways. And you can have brain stimulation treatments, right? Well, a few years ago, the FDA approved the first ever treatment for postpartum depression, brexanolone. It is a drug that, when given intravenously to women who are suffering from severe postpartum depression in the hospital, they get better within three days. This is precision medicine. Why? Because we don’t take women with depression and treat them with this drug. We only treat them with this drug in the postpartum period, because that’s a different kind of depression that we have now recognized and identified. And, uh, women with postpartum depression will respond to this drug better than women with other kinds of depression. So, this is the first example of precision psychiatry. It’s an easy one, right? You can easily identify who is having depression after they give birth as compared to other things. And we still need to do a better job. Not every woman with postpartum depression will respond to brexanolone, and maybe they need something else instead, but it’s a good first step. I think we’re going to see more and more examples of precision psychiatry as we move forward.
Gabe Howard: Obviously, I spent the beginning part of this podcast pointing out that there’s no definitive test for serious and persistent mental illness like bipolar disorder, schizophrenia, and the like. But we’ve learned a lot of things because of this research. Can you share some of that research with us? Where are we going? What have we learned? What progress have we made?
Dr. Joshua A. Gordon: Well, let me get let me switch from bipolar for a moment to another serious mental illness, schizophrenia, where I think it’s easy to see how that progress has moved the needle. So, in schizophrenia, like bipolar disorder, your likelihood to get the illness is partly due to genes and partly due to environmental factors like bipolar disorder. We have some idea of the environmental factors. We’ve made tremendous progress on the genetic factors. In schizophrenia, for example, there are well over 250 places in the genome, each one of which is likely representing one or more genes well over 250 places in the genome where we know that something is going wrong in that place, that raises your risk for schizophrenia. There’s a dozen or so places in the genome where not only do we know that something is gone wrong there, but we know exactly what went wrong there. And we can study those factors in biological pathways, in experiments that will really make a lot of progress. But even without moving to that next step, we can look at those places in the genome and we can ask. What? What do we learn from just identifying these factors? We learn, for example, that the fundamental timing of when risk for schizophrenia plays out in an individual is much, much earlier in life than we would have thought.
Dr. Joshua A. Gordon: We’re talking about during fetal development when the when the baby is developing in its mother’s womb, that’s when these genetic factors are playing out. Raising your risk for schizophrenia, even though schizophrenia is an illness, doesn’t really emerge until late adolescence, early adulthood. So that’s a fact that we have learned, which then leads us to look earlier in biological pathways than we were looking before. Another thing we’ve learned is that these places in the genome point to a particular biological process, the communication between the cells of the brain, between neurons as being disrupted in schizophrenia. And so that allows us now to study those pathways that are involved in that communication and get further along the biological understanding. And it has also caused us to start looking at drugs which affect that communication as possible new tools in the treatment of schizophrenia. And although none of them have yet been approved or anything like that by the FDA, we don’t yet know if they’ll really work. We’ve begun to examine a whole new classes of drugs that might really change the game for schizophrenia treatment in, in, in, in the near to midterm future. So, with genetic understanding comes the ability to ask new questions and potentially new treatments arising from that.
Gabe Howard: I really feel like part of my job as a mental health advocate is to constantly point out the side that’s being missed. And as you are probably aware, pharmaceutical companies have a lot of money to advertise. So, we tend to see the medical model over and over and over again. Whereas environmental things, therapy, things like how we’re relating to trauma, how we’re responding to the world, even how our age or socioeconomic status or race impacts us doesn’t quite have the same amount of advertising money to push behind it. So, people tend to forget it. How can we get people to move more towards the middle to understand that we need to be paying attention to both environmental factors and biological factors. And even though we’re researching a lot of biological factors right now, which is extraordinarily important, but I do feel like we need to spend at least a moment on the idea that we need to have research into the environmental side and how it’s impacting the biological side.
Dr. Joshua A. Gordon: That’s a great point and you’re 100% correct. So, you asked, how do we get people to understand that complexity and integrate other kinds of information into their thinking and also into the research.
Gabe Howard: That is a much. That is a much quicker way. Yes, yes. You speak. You speak shorter than I do.
Dr. Joshua A. Gordon: [Laughter]
Gabe Howard: I like that.
Dr. Joshua A. Gordon: Well, I’m trying to tell you the truth. I’m trying to make sure that I get the question in my own head first, so I’m going to restate it like that.
Gabe Howard: You nailed it. You nailed it. Thank you, Josh.
Gabe Howard: And we’re back with the executive director of the National Institute of Mental Health, Dr. Joshua A. Gordon.
Dr. Joshua A. Gordon: So first and foremost, these kinds of conversations, Gabe, they really help. Right. Let’s get it out there in the open. Yeah genetics is important. So are these other things. Yeah these other things are important. So is genetics just talking like that with our patients, with advocates, with our friends and relatives. That’s really, really important. Yeah I have bipolar disorder and probably a part of that runs in my family. But also, there were experiences that I had in life that may also explain some of it. Right. So that’s those kinds of conversations can be really helpful. On the research side, you also hit the nail on the head. We need to support research not only into genetics but into other causes as well. Let me give you one example. Since we’re talking about trauma, the National Institute of Mental Health has supported now a study called the AURORA study, which seeks to understand how people who are exposed to horrible traumas develop post-traumatic stress disorder or don’t develop post-traumatic stress disorder. So, we take individuals who are seen in emergency rooms after horrific incidents, whether it be rapes or automobile accidents or other traumatic experiences, and they’re in the emergency room. We recruit them into the study, they get their genetics done, they get some brain imaging, they get some blood tests, and they get lots and lots of questions about their living situation, about how they grew up and where they grew up and what adversity they faced. And then we follow them over the next two years to see what changes happen in their brain, what changes happen in their blood, what changes happen in their living situation, and then try to figure out what combination of genetics and environmental factors and response to stress predicts, whether they’re going to develop a mental illness after this trauma or whether they’re going to be resilient to it. And we hope through this study that we’re going to learn a lot about these biological and other factors that contribute to illness so that we can develop better ways of improving resilience.
Gabe Howard: Improving resiliency and improving outcomes is the number one goal of every person living with mental illness. Josh, from your perspective, is the. As the executive director of the National Institute of Mental Health, how far away are we from getting there?
Dr. Joshua A. Gordon: Like you point out, we’ve made some gains in some areas. As you know, there are drugs that work very, very quickly now for depression. Um, they can be a little challenging to get. We need to work better on making sure that people have access to drugs like ketamine and brexanolone, uh, for treatment resistant depression or for postpartum depression that can get people read better within a few days, which is a step in the right direction. But they don’t work for everybody, and they’re expensive and they’re not available everywhere. So different parts of research need to be done on those treatments. Schizophrenia is a really tough one, to tell you the truth, because as I said earlier, what we know about schizophrenia is that it develops in the womb and early, early in life and doesn’t manifest until 20 years later. And so, what we’re trying to do 20 years later is unravel all the different things that likely happened over the development of that infant and that child and that adolescent. And that’s I think I don’t have any prediction about when we’re going to be able to do that easily or quickly. At the same time, we have made progress using the tools that we already have. Um, we now have a nationwide network funded by the Substance Abuse and Mental Health Services Administration that that funds first episode psychosis clinics in every state in the United States. And those first episode psychosis clinics are reducing the amount of time that people spend in psychosis during their first episode. It is improving the ability of these individuals to go back to work, to go back to school, to go back to their families. And so, we have that moving forward. It’s not a magic bullet, but it’s at least a step in the right direction.
Gabe Howard: Thank you. Thank you so much, Josh, for explaining that. And I want to sort of piggyback on that a little bit. Anybody who’s listened to me talk for a long time or listen to this show for a while, has heard me pound the drum of why are all our advancements serendipitous? Why are they all serendipitous? They’re we’re looking for a cure for one thing, or looking to treat something else. And then during the studies, we find out that it helps somewhere in the mental health field, we isolate that and move on. But of course, your organization, the National Institute of Mental Health, it’s frontline research for mental illness, for mental health issues and for mental disorders. And you’ve made this a real priority like probably you personally, Josh, but the National Institute of Mental Health has made genomic research a real priority. First I want to ask why have you prioritized this?
Dr. Joshua A. Gordon: So, we’ve prioritized genomic research because, number one, its genes play a role in every single mental illness, even ones you think of as totally environmental, like post-traumatic stress disorder. Right? That’s a disorder that happens because of a trauma that you go through. Even PTSD has a component of it that is genetic, right? So, if we study genes and how they affect the brain and how they affect mental illness, we can learn a lot about all mental illnesses. That’s number one. Number two, genes are easy to study. They are although it might seem expensive, they’re relatively cheap to make progress on. We can get genetic information on literally hundreds of thousands of people in ways that are much easier to do, much less expensive to do than getting other kinds of information about so many people. Number three, genes give us direct inroads into the makeup of the brain. When we identify a gene at risk, we can then go right into the cells of the brain and ask, where is that gene expressed? We can study how that gene influences all the different biological machinery of the brain. It’s really, really powerful in terms of moving from that factor to a biological understanding. So, we’ve made tremendous progress because of those three advantages. Number one, genes play a role in all mental illnesses. Number two, they are relatively easy and relatively cheap to study. And number three, they provide clues into fundamental biological aspects that we can follow up on in a straightforward way.
Gabe Howard: Josh, just out of curiosity, I remember when I was younger and, you know, I’m gonna I’m gonna I’m gonna let the audience know that apparently I’m old, but when I was younger, there were no DNA tests to establish paternity. There was a blood test for paternity, but it could only exclude the father. It couldn’t include the father. And I’m. I’m curious. Are we at least moving in that direction with mental illness? I understand that there’s maybe not going to be a definitive test for schizophrenia, bipolar disorder, anxiety, major depression, OCD, etc. but is there at least something that can exclude it? Like to figure out if you have the markers for it or don’t have the markers for it, so they can’t tell that you definitely have it, but could they tell that you definitely don’t have it? I’m just curious about that form of science, or at least looking at this from that approach.
Dr. Joshua A. Gordon: That’s a great point, Gabe. It sort of puts our usual thinking, turns it on its head, and asks, well, if we can’t say you do have an illness, can we rule it out? Unfortunately, I don’t think we’re there yet either. Where we are is when we think about, particularly with genetic tests, but really, any of the ways that we have to look at illness, the best we can do right now is change the likelihood. The probability. Now, in reality, that’s not different than most of medicine. Let me give you an example. There’s been a lot of talk over the years about how much cholesterol is bad for you, right? And if you have too much cholesterol, they give you a diagnosis. They call it hypercholesterolemia. Right. And they give you a treatment, a drug to lower your cholesterol. But why do we care about cholesterol? We care because it raises your risk. For a heart attack or a stroke. Now, the reason there’s arguments about what exact number is an important to diagnose hypercholesterolemia is because that number doesn’t tell you whether you’re going to have a stroke or not. It tells you what whether you are more likely or less likely to have a stroke. And that’s where we are with these tests right now. I could if I wanted to or if you wanted to, you could get your genome sequenced and we could pull out all the data from your genome that’s relevant for bipolar, Gabe. And it would give you a rough likelihood if you will. But it’s not going to definitively say you have it or you don’t. And we’re not there yet. In truth, I don’t know that genes can really get us there, but maybe a combination of genetic and other information about an individual will get us to something that’s closer to what we’re looking for in terms of definitive diagnoses.
Gabe Howard: It’s sort of making me think of cigarettes and lung cancer. We always hear that smoking causes lung cancer. I mean, you know, when I was a kid, if I went near a cigarette, my mom would say, you’re gonna get lung cancer. But. But I do think that we understand that it’s not 100%. Not every single person who smokes is going to get lung cancer. And we do understand that many people who never smoke can, in fact, get lung cancer. Is that sort of a good layperson’s analogy for maybe how mental health is both environmental and genetic?
Dr. Joshua A. Gordon: Yes, I think it’s a really good example. Smoking cigarettes raises your risk for lung cancer. It raises your risk a lot for lung cancer. But just because it raises risk doesn’t mean that you are definitely going to get lung cancer. But it does mean that you’re more likely to get it. And if you don’t smoke, you could still get lung cancer. It’s just that it happens much less often if you don’t smoke. There’s another thing, Gabe, that I like about that analogy. Smoking doesn’t only raise your risk for lung cancer, it also raises your risk for other health problems like stroke, emphysema, and other forms of cancer. Also. Smoking isn’t the only thing that raises your risk for lung cancer. Radiation raises your risk for lung cancer, and genetics raises your risk for lung cancer. So, in that way, using this example of lung cancer, which I think most people are able to understand, you can sort of understand what the role of genes and other factors might be in mental illness. It’s very, very similar in that way.
Gabe Howard: Josh, thank you so much for being here.
Dr. Joshua A. Gordon: Thank you for having me, Gabe.
Gabe Howard: You are very, very welcome, Josh. And of course, to all of our listeners, thank you so much for being here. You can learn more about the National Institute of Mental Health by visiting their website
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