Why Aren’t There Biomarkers For Mental Illness?

Hey, it's Flora Lichtman, and you're listening to Science Friday.

Today in the show, despite major advances in understanding the biology of mental health disorders, there's no blood test or brain scan that will confirm if you have depression, anxiety, PTSD. or other psychiatric illnesses. And yet the next version of our diagnostic Bible, the DSM, the Diagnostic and Statistical Manual of Mental Disorders, will include biomarkers. So how close are we to pinpointing the biological markers of mental illness and what does that mean for diagnosis?

It's complicated. Here to untangle some of the science for us is Dr. John Kristol, Professor of Psychiatry, Neuroscience and Psychology at the Yale School of Medicine, based in New Haven, Connecticut. John, thanks for being here. Well, my pleasure, Flora. Okay. John, how hard is this problem, the biomarker for mental illness problem? It's an enormously challenging problem. Uh you know, some people say that the brain is the most complicated structure in the universe.

And we're trying to uh decipher the codes that underlie the symptoms and challenges that people uh experience in their lives and and therefore it's an enormously challenging problem that we've been working on for a long time.

Well what why is defining biomarkers for mental illness so difficult compared to other illnesses? Well, one of the reasons is because we are usually not analyzing the exact tissue that we're uh interested in. In other words, if you have a tumor, they would do a biopsy and analyze your cells to find out exactly what the molecular signatures of your illness are.

And that helps to make sure that you get the treatment that you individually need. That's what we'd like to go for in psychiatry, um, to apply something that people call precision medicine. Um but we we have to do that without sampling your brain tissue because you probably don't want us to do I mean, if you could sample brain tissue, would you be able to pick out biomarkers? Like, is that even the way that we would be able to understand um a psychiatric disorder? Believe it or not.

We are analyzing the uh brain tissue and it's an enormously complicated task, but we're not uh biopsing people's brains. What we're doing are that there are some people who have been extremely generous in donating their brains to science, and we're analyzing their brain tissue. and uh identifying the signatures of individual cells and progressively the molecular signatures of individual cells in particular circuits in particular parts of the brain.

to help us unravel what is, I think, emerging as the first true molecular understanding of the biological basis of psychiatric disorder. And and what disorders are we talking about? I mean, even for something like depression or anxiety? Absolutely. In fact Here in Connecticut, uh at the VA Connecticut Health Center in uh West Haven, we've done the first

a molecular analysis of post-traumatic stress disorder and comparing it to a disorder like depression. Both illnesses have depression as a symptom, but it turns out that the underlying molecular signatures of of depression and PTSD are are somewhat although they overlap a fair amount, they're still in important ways differ. Really? That's I mean, I wondered if one of the challenges is that

mental health disorders vary so much. Even within one condition and, you know, across conditions you have these overlapping symptoms. Does that make the search for biomarkers more difficult? Yes, I think I think that is one of the enormous challenges that we face. You know, I I think that I the DSM five has something like two hundred and seventy or so different ways that you can make the criteria for major depression. And that that includes people who are sad all the time.

or people who are generally in good mood but react strongly to bad news, or or people who uh just lack energy and and don't feel necessarily sad or depressed. So there are a lot of different ways to meet a given diagnostic criteria and and probably many, many different biologically different subtypes of problems like depression or anxiety.

Are there mental disorders that we have really reliable biomarkers for that we can use for diagnosis? Well, uh if you think of psychiatry broadly as I do, then one of the disorders that psychiatrists are often involved in treating is uh Alzheimer's disease. And there there is a real success story where there is a a PET scan you can do that helps to identify a level of a chemical that's accumulated in the brain associated with Alzheimer's disease.

To help to make the diagnosis of Alzheimer's disease in a very specific way. And what's important about this? is that when you're developing uh memory problems and you have this emerging diagnosis of Alzheimer's disease, there's something that we can do for you now to slow the progress of your memory problems. So in the ideal world What we're trying to get to is that kind of precision in our diagnosis process so that we can get people.

uh the best help that we can. Because it helps with treatment. Because it helps with treatment, exactly. And it also helps to frame expectations. when we know that someone is evolving Alzheimer's disease, that that's important information. that uh people need to help prepare their estate and their families and things like that. So understanding what you're going through is very empowering and it it helps people to cope as well.

For other conditions, what biomarkers are you looking at? Is it like signals on fMRI or blood tests? And what seems promising? You know, I I tell the applicants to our residency program that this is the the most exciting moment in the history of the field of psychiatry, literally, because all of the areas that you just mentioned, blood test, uh genetic analysis. Um functional magnetic resonance imaging, structural brain scan.

PET scans to measure the level of various proteins in the brain, et cetera, et cetera. We're using every kind of information that we can collect. to try to uh better understand and and subtype the the various psychiatric diagnoses. Um and we're on the cusp of using data that people collect, like uh where the their daily pattern of activity, where they go, their level of social interaction.

uh much more detailed granular uh behavioral information to integrate with all this other information to help us to um better inform diagnosis and treatment. The genetics must be so difficult though, right? Because if I understand correctly, there's so many genetic variations that can play a role in mental illness. It's not like a gene.

Right. You're you're absolutely right. In in fact, there are many different ways that uh genetics can uh increase the risk for psychiatric disorder. Probably the one that we've made the most progress on so far is schizophrenia. So about three to per three to five percent of the people who have schizophrenia have a rare, rare, rare mutation in a gene that increases their vulnerability uh for schizophrenia fifty or a hundred hundredfold even.

But that's a very small percentage of the people with schizophrenia. Most people who develop schizophrenia. have a whole collection of common variants that individually have a trivial a contribution to their risk for developing schizophrenia. And there are about four hundred and fifty different common variants in this way that contribute to the risk for schizophrenia. Four hundred and fifty. About four hundred and fifty, right.

Right. And so vi different people who are developing schizophrenia may have uh a collection of these various risk uh variants, but they may not have the same ones. And and and so that contributes to heterogeneity as well.

Is the difficulty finding specific biomarkers for specific conditions, does that suggest that maybe the way that we categorize mental illness isn't quite right? Yes.

you know, if we think of psychiatric disorders the way you might think about um breast cancer, there was a time when we diagnosed breast cancer by finding a lump and trying to do something. Now we Get the tissue, genotype the tissue, find the mutations, and characterize other aspects of the tumor, and so we can really target in a very specific way.

Right. There's not one kind of breast cancer we have. Exactly. Exactly. And it makes a big difference in terms of the kind of treatment you get for breast cancer. In psychiatry, because we're diagnosing today based on behavior, it's analogous to diagnosing breast cancer based on the lung. And and so what we're trying to do is to get as much information to help us to get to the point um where we can make uh diagnoses with the same precision

for depression that we currently do for breast cancer. And and I think that's going to come. I mean, given what we've been talking about, do you think the science is at a stage where it's ready to be incorporated into the next DSM? Or is that sort of aspirational and helps push the field along? It it's mostly aspirational in the sense that few of the of the biological findings that we have are really ready to implement.

in the in the average uh doctor's office in their everyday work with patients. I think though that one of the things that I admire about the process that the American Psychiatric Association is engaged in. is they're trying to set the stage for the emergence of uh many of these biomarkers as they mature so that psychiatric pr practice is anticipating their arrival and is ready to in incorporate them in the diagnostic scheme.

Doctor John Crystal, Professor of Psychiatry, Neuroscience and Psychology at the Yale School of Medicine based in New Haven, Connecticut. My pleasure. Thanks for having me. Today's episode was produced by Shoshana Bucksbaum. And if stories like this help feed your brain, please leave us a review on Apple Podcasts or Spotify or wherever you listen. It helps other folks find the show. Thanks for listening. I'm Flora Lichtman.