Dr. Javier Escobar, associate dean of global health and professor of psychiatry and family medicine at Robert Wood Johnson Medical School, is leading a research consortium that recently secured a prestigious $5.5 million 2017 NIMH award to try to pinpoint the complex genetic causes of severe mental disorders like schizophrenia—a discovery that could change the way psychiatric diagnoses are made. We spoke with Dr. Escobar on the research, its potential impacts, and the importance of international collaboration.
Congratulations on this award! We talked briefly about this research, “Colombia-US Cross Disorder Collaboration in Psychiatric Genetics” when you were on our TV show, Rutgers Around the World, and now it has been funded by the National Institute of Mental Health (NIMH) for $5.5 million. I understand this research will take place in Colombia. Who is involved in the research, and why go abroad for this study?
JE: This funding that we received for five years, $5.5 million, was the largest amount that the National Institute of Mental Health (NIMH) awarded this cycle—it’s very hard to get funded by them. The major aim of this study is to look at the particular genes that seem to lead to certain disorders, such as bipolar disorder, schizophrenia, other psychoses, and major depression with psychoses.
Colombia that is my native country. That may be the main reason why over the last two decades, I think, I’ve had collaborations there that gradually increased and included other institutions.
Through the years, because the work we do is on the genetics of mental disorders, we initiated a collaboration with a local university in Medellín, Colombia, called the University of Antioquia. It is one of the leading research universities in Colombia—I graduated from there, actually.
So, together with the University of Antioquia, we assembled a consortium that includes UCLA and the University of California–San Francisco. I am the PI for Rutgers, and I am the glue that connects the U.S. investigators with the local investigators in Colombia.
Going abroad to do scientific studies is not new; the gene for Huntington’s Disease was found in Venezuela by American investigators who went there to look at, to a large extent, a family system in Venezuela. And many other disorders have been identified or studied outside the United States, or outside the European countries.
I’ve been building these international collaborations for decades, so this is not something that can be improvised. This has taken time, connections, collaborations—many things have had to happen to bring us to this space.
How will you conduct the research and what do you hope to find?
JE: We are going to study a special population in Colombia’s coffee-growing (northwest) region that is called the Paisa population. They have large, extended family systems that have been living in this region for generations.
Here, we can identify patients with severe mental disorders, and we can have access to their parents, grandparents, and children. Genetic studies in special populations are very important because you decrease variability, you get more homogenous samples, and you’re able to look more clearly at the effects of genes compared to the effects of the environment.
The major aim of this study is to look at the particular genes that seem to lead to certain disorders, such as bipolar disorder, schizophrenia, other psychoses, major depression with psychoses. We are going to study 8,000 people—8,000 patients with severe mental disorders that require them to be hospitalized. Then, we are going to look at 2,000 controls—people that have never been hospitalized for psychiatric reasons and have no history of mental disorders.
The genetic studies are very sophisticated and of course the reason we are able to do it is because, for the last decade, we have been collaborating in some other genetic studies just trying to define phenotypes—phenotype is the visible manifestation of a genetic influence.
So, in this case, we call it endo-phenotype because it includes a number of factors like thickness of the brain cortex, genes, circadian rhythms, sleep, and physical activity.
For the last decade, we have been studying all these components so we have a number of phenotypes that seem to be related to genes.
Five years is a long time. What are the phases of the research?
JE: The study began in June 2017 and it goes through June 2022.
We are studying the Paisa subjects and the control subjects for some time, conducting interviews, asking about symptoms, takings blood tests to look at genes, doing some brain imaging studies, and using FitBit gadgets to measure health and physical activity—sleep, or how much people move, counting calories they spend, and so on.
Why does it take five years? To collect this data from all of these people takes a long time. We hope to cover maybe 2,500 people a year for the next four years—the last year will be for the statistical analysis of this data. Currently, we are training people and developing the instruments.
We talked about the phases of the research. Now that you’re looking to identify the genes that cause or “turn on” schizophrenia and other major mental disorders, do you have a theory about what genes could possibly be the cause?
JE: Psychiatric diagnosis is very complicated. I know the news media thinks that psychiatric diagnosis is the most precise thing—it’s not. It’s very subjective.
With the exception of Alzheimer’s, where you can see the amyloid clumps in the brain, there is nothing like that in schizophrenia or depression or bipolar disorder that tells us that it is what it is, like we do with an infectious disease like HIV. So, what we are trying to do is make it more objective, to see if there are some markers that we can measure that are going to help us to support a diagnosis.
We already know that these disorders have a genetic component from studies of identical twins. If one twin has a severe mental disorder, we’ve seen that 50 percent of the time, the other twin also develops the disorder.
So, we may find some potential markers that are measurable that could tell us that a person is suffering from a subtype of bipolar disorder or a subtype of schizophrenia that’s more related to genes or that’s more related to environmental influences. So, we are going to dissect subtypes of disorders as possibly related to Gene “X” or Gene “Y” and so on and so forth.
There’s not a single gene for a single psychiatric disorder, so that’s what makes it complicated. In fact, there are more than 20 or 25 genes identified that may be important for schizophrenia, but how they work and how they operate, we don’t really know yet. By doing studies like this one, we may be able to control for many variables, because this a very homogeneous population that has been there for generations—we know the genetic influences.
Are there other studies being conducted on the Paisa population?
JE: I think something very important when you write the article is to tell people that this Paisa population is now the place where the most important research on Alzheimer’s is being conducted, possibly the whole world.
They are trying to see if an intervention on people who have the genes that develop this form of Alzheimer’s could stop the disease. And the investigator doing that is a neurologist who collaborates with us as well—Professor Francisco Lopera, a behavioral neurologist at the University of Antioquia. He is working with several U.S. institutions, and they’re doing this massive study on Alzheimer’s disease—there are about 5,000 people who are affected by a gene that causes Alzheimer’s before the age of 50.
So, if you have that gene, you develop Alzheimer’s. It’s a dominant gene—only a minority of cases of Alzheimer’s are related to specific genes, but this one we know, and we have classified. So, the idea is then if you identify cases of Alzheimer’s, they have the gene, and then they have children who have the gene.
Then, you start treatment on them that prevents the deposit of amyloid in the brain. So, what we are hoping that maybe you could stop the disease by giving them medication early enough. So, that is still ongoing, so we don’t have the results yet. There have been many articles on this kind of work, so we are hoping that our study on severe mental disorders in Colombia will appear on 60 Minutes and in the New York Times—but we’ll make the Rutgers Global newsletter first!