A new episode of our podcast, “Show Me the Science,” has been posted. These episodes feature stories about groundbreaking research, as well as lifesaving and just plain cool work involving faculty, staff and students at Washington University School of Medicine in St. Louis.
In this episode, we report on a major international study involving psychiatry researchers from the School of Medicine who are working to identify causes and effects of the early stages of schizophrenia in young people — an illness characterized by significant changes in thoughts, feelings and behavior that may include a loss of contact with reality. The goal is to improve early diagnosis and treatment to potentially prevent the most devastating effects of the disorder.
The study’s principal investigator is Daniel Mamah, MD, a professor of psychiatry. He has a clinic in St. Louis, where he works with young people to identify biomarkers in the blood and the brain that may help predict risk of debilitating psychiatric illness. He also studies potential drug targets for treating such conditions.
In addition, Mamah and his colleagues have expanded their efforts to East Africa. Working with collaborators in Kenya, the researchers are launching a site in Africa to study young people at risk for schizophrenia in hopes of learning more about what causes the illness, as well as how to potentially prevent it. Mamah previously has collaborated with researchers at the Africa Mental Health Research and Training Foundation, and now the scientists are working to identify and compare risk factors for schizophrenia in patients from North America and from Africa.
The podcast, “Show Me the Science,” is produced by WashU Medicine Marketing & Communications at Washington University School of Medicine in St. Louis.
The free clinic is one the Midwest's few specializing in conditions such as schizophrenia and bipolar disorder in youths
Jim Dryden (host): Hello and welcome to “Show Me the Science,” conversations about science and health with the people of Washington University School of Medicine in St. Louis, Missouri … the Show-Me State. In this episode, we look at the ongoing work to identify young people at risk for serious psychiatric illness such as schizophrenia before they get too sick and their illness becomes more difficult to treat. People with schizophrenia often have psychotic symptoms, which can cause them to be confused about what’s real and what’s not. Hearing voices that are not there, for example, is frequently a symptom. As early detection has become a watchword for those who work in cancer care, diabetes and throughout much of medicine, for a few years now, Washington University psychiatrist Daniel Mamah also has been trying to identify high-risk young people in a clinic that’s dedicated to those young people who are at risk.
Daniel Mamah, MD: Psychotic disorders tend to be progressive. That means that over time they tend to be worse, especially if they’re not treated, which is the whole point of this clinic. When it begins, at that young age, it tends to be a little bit more episodic. The frequency of these symptoms tends to be less, and so they could present in a scenario where they would, say, hear sounds that other people don’t hear, and for the next several days, they don’t complain about it. And then it happens again. Oftentimes it becomes more and more frequent over time.
Dryden: Mamah says young people at risk for serious illness like schizophrenia often can be identified by parents, teachers and other trusted adults who notice major changes in behavior. In fact, that’s how the clinic gets most of its referrals.
Mamah: Everybody is going to have a different sort of experience with this. But generally, there would be a change in the way that person behaves or thinks. A parent would say, “My son has been behaving differently for the last year. He used to be very outgoing. Now, all of a sudden, he’s kind of withdrawn. He’s beginning to become more suspicious of us, of people around him. He’s beginning to not do as well in school.” In someone else it may be, “He’s beginning to look like he’s responding to internal stimuli,” where he would be, say, talking to himself, for example. So the brief is, it would be some sort of a change from their existing way of behaving. Schools would be a very big referral source for us – high schools and colleges. But sometimes it would be just a family member saying, “I think my son or daughter fits the profile.” We would kind of ask them some questions. If needed, would bring them in and put them through more detailed assessment just to make sure that this clinic would be a good fit for them. And if they do fit, then we would get together with the staff and try to figure out what would be the best, individualized treatment approach for that individual patient.
Dryden: Treating and studying young people at high risk, Mamah and his colleagues are working to characterize the symptoms and traits that might help identify psychosis risk early. In addition to providing clinical care such as antipsychotic medications and psychotherapy, Mamah is a key investigator in a large international study of those at high risk. He says it’s important to identify the people who may be at risk because there are a lot of them. About 100,000 young people in the United States experience a first episode of psychosis every year. Mamah has been studying such patients in St. Louis with the goal of identifying patients at risk for serious problems down the road.
Mamah: There is this large NIH-funded study. It’s called the Accelerating Medicine Partnership for Schizophrenia, and there are 42 international sites, of which Washington University is one. And I direct that site.
Dryden: And once they get at-risk patients into the clinic, each patient receives individualized treatment, and Mamah says if they choose to, most patients also can participate in research designed to learn more about schizophrenia with the goal of improving outcomes down the road.
Mamah: We’re WashU, so we always try to see if we can learn something from any kind of clinical situation we have. They would have a psychiatrist, if they need one, get counseling. They would get casework if that’s necessary for them and other potential services.
Dryden: And now Mamah has begun directing a similar study site in Kenya. It’s the first study of its kind on the African continent. On a recent morning in St. Louis, which already was early evening in Kenya, Mamah was on a Zoom call, checking in with colleagues in Kenya.
Mamah: So are there any updates with this study in Kenya? Anything to report?
David Ndetei, MD: Yeah, Victoria’s got a lot to report.
Victoria Mutiso, MD: And there’s going to be quite a bit coming shortly in the next couple of weeks. But what I have to report now is that we have already dived into the rural areas to recruit the high schools.
Dryden: On the call with Mamah was Dr. David Ndetei, a professor at the University of Nairobi and the founding director of the Africa Mental Health Research and Training Foundation. Also on the call was Dr. Victoria Mutiso, who is a research and administrative director at the same foundation. They’ve begun recruiting young people in urban and rural areas of Kenya, looking for markers of risk and hoping to identify ways to prevent those young people from advancing to serious psychotic illnesses. Ndetei says recruitment has been going very well, as the people in Kenya have been lining up to volunteer for the project.
Ndetei: People are very interested in things to do with mental health. And then from this office, we do a lot of mental health awareness across the country and beyond Kenya. In fact, we have a family TV station that records me, and they broadcast on mental health awareness every Friday, and we have been doing that for the last two years.
Dryden: This is not the first collaboration between Dr. Mamah’s lab and Dr. Ndetei’s group in Kenya.
Mamah: I have been working with this group in Kenya for, I want to say, about 11 years, maybe a little more. And we have done a lot of work related to psychosis and psychosis risk. And so this is the continuation of some of the work that we’ve been doing there.
Dryden: Is it known, are rates of psychotic illness in schizophrenia in a place like Kenya similar to what they would be in a place like St. Louis? Or is that one reason to do the study, to find out?
Mamah: I wish I had a direct answer to that, but the problem is we don’t really know. And the reason for that is there haven’t been a lot of epidemiologic studies in Africa looking at rates of schizophrenia. Now, the limited studies that have been done in Africa show that the rates are comparable to the rates in other countries. But again, we need to do more studies to have a better answer to that. However, in other countries, in Europe and in the United States, rates of schizophrenia are higher among people who are Black or have African ancestry. Now, again, that could be for a variety of reasons. It could be related to unique environmental stressors or even biased assessments. But it really just gives us a reason to want to do more studies in Africa so that we can get a better understanding of differences across populations. So really, it was just a matter of need. There’s a big need to do research there. And we’re sort of seeing similar research in other parts of the world. And we felt there was an opportunity to do that. So I think that that’s really the main reason. There are also personal reasons why I wanted to do research in Africa. My dad is from Nigeria. But really, the main driver has been just this opportunity to do something that has been missing in the research field.
Dryden: And you and your colleagues traveled over to Africa recently, and you’ll be going back soon. Tell me about that. What was that like?
Mamah: I mean, it’s always a great experience going back. The weather is a lot better. So that’s one part of it. But really, it was very productive this last time that we went back. But we really made a lot of progress, really building an EEG biomarker laboratory in Kenya. So we really built this from scratch. We used a shipping container, a large shipping container, and we really transformed this into a several-room laboratory that will be used to collect EEG data. So some of the rooms were padded. The other parts of the lab would be used to collect other biomarker data like saliva and things like that. So it’s really already made a really big difference in Kenya, because we will be able to use the lab for studies beyond this one. We were also able to upgrade the 3T MRI scanner that we’ll be using. And so now we will be able to collect high-definition brain images. So we’ll be collecting structural imaging, functional connectivity, as well as diffusion imaging. So we will be able to get really high-quality information about brain connections and brain structure.
Dryden: In someone with schizophrenia, often various key parts of the brain may be smaller or bigger, and in addition to that, the brain isn’t communicating with itself the way it would in someone who’s healthy, correct?
Mamah: Generally, in schizophrenia, we do see that a lot of brain regions tend to be smaller in some way, and the communication between different brain regions tends to be more disorganized than in people who don’t have the illness. And so what we’re hoping to do with this study amongst many things is, can we identify patterns of brain structure and brain connectivity that may predict who will develop schizophrenia, maybe even before these symptoms become very prevalent?
Dryden: I did see some of the pictures that you sent, and I couldn’t tell — is this a rural area? Is it an urban area? Where are you setting up? And is there one site? Are there several?
Mamah: There are several sites. So the recruitment in Kenya is going to be a little bit different than the way we do it in St. Louis and the way it’s done in a lot of sites. So we will have multiple different communities where we will be recruiting from. It’s going to be cities. It’s going to be suburban-type locations as well as smaller villages. So we are really trying to be as diverse as possible within Kenya. However, there are certain parts of this study that would require the research participants to come to Nairobi, which is the capital. So the parts of the study that involve brain imaging or EEG acquisition, that would require transporting the participants to the big city. But most of the assessments will be done locally within their individual communities.
Dryden: This might just be me with my American blinders on, but my impression is that as great as the need is in the United States here, that it might be even greater in Africa.
Mamah: The need is a lot greater in that continent. And one of the reasons for that is that there seem to be other priorities that take precedence over mental health or investing in mental health care and mental health research. So the infectious diseases and some other medical conditions — that has been attended to a lot more than mental illness. So now that is changing, but it’s still a big difference from the way things are in the United States. There’s also a lot more stigma about mental health than there is here. But again, it’s slowly moving in the right direction. So the way we plan to do this, or the way we are doing this, is we’re screening 12,000 people from the community. So you can imagine from 12,000 people we need 150 high-risk people. So we have a lot more people to, kind of, pick from. And so the screening, we already have about 4,000 people screened. I think we will probably get to 12,000 in the next six months or so.
Dryden: That seems a lot faster than on this side of the water.
Mamah: Community screening is a lot easier in Kenya than it is in the United States. There tends to be a lot of interest in participating in the screening with almost no participant refusing to be screened. And so that has really made research a little bit easier for us.
Dryden: Is there a general rule of how you would encounter someone like this? Is it somebody who doesn’t want to admit that they’re having this problem? Or is it somebody who’s looking for help, or does it vary person to person?
Mamah: It does vary from person to person. I mean, generally, this is a recruitment challenge because a lot of people who have these attenuated symptoms do not have a psychiatrist, or they are not seeing a provider because the symptoms are not severe enough. They usually don’t end up in a hospital or any kind of urgent center. They’re having these low-grade kinds of symptoms. So a lot of times people don’t realize that they have a problem or that it’s something that needs to be looked into. A lot of times these symptoms are associated with functional decline. So a lot of times these tend to be teenagers, often. And so a lot of times there’s a change in their social behavior in school that the parents recognize. So usually, there are things like that that lead a family member, usually a parent, to identify that there’s something going on. But unfortunately, a lot of times they don’t seek care until symptoms have advanced.
Dryden: The goal eventually is to identify people sooner. Mamah says psychiatrists want to treat psychotic illnesses like schizophrenia as early as possible. That’s what he’s trying to do both at his clinic in St. Louis and on the other side of the world in Kenya.
Mamah: Like any illness out there, the earlier you intervene, the better the long-term outcomes are. Particularly for psychotic disorders, there have been a lot of studies that show that the earlier that you can intervene, the long-term outcomes, 10, 15 years going forward, are much better for the individual.
Dryden: “Show Me the Science” is a production of WashU Medicine Marketing and Communications. The goal of this project is to introduce you to the groundbreaking research, lifesaving, and just plain cool work being done by faculty, staff and students at the School of Medicine. If you’ve enjoyed what you’ve heard, please remember to subscribe and tell your friends. Thanks for tuning in. I’m Jim Dryden. Stay safe.