Science Friday - How Do Antidepressants Work, Genetic Testing For Depression. Sept 16, 2022, Part 1

Episode Date: September 16, 2022

Why The Owner of Patagonia Gave Away The Whole Company Earlier this week, the founder and owner of Patagonia Yvon Chouinard—the company known for their famous puffer jackets and outdoor gear—gave away the whole company. Who’d he give it to? The Earth. “Hopefully this will influence a new form of capitalism that doesn’t end up with a few rich people and a bunch of poor people,” Chouinard told David Gelles for The New York Times. “We are going to give away the maximum amount of money to people who are actively working on saving this planet.” Purbita Saha, deputy editor at Popular Science, debriefs Ira on Chouinard’s decision, as well as other science stories of the week. They talk about if it’s safe to get the COVID booster and flu shot at the same time, how a new blood test could catch early stages of cancer, why the night sky is bluer, the reason why NASA is crashing a spacecraft into an asteroid, and the fight over trash between cockatoos and Australians.   Depression Isn’t Caused By Low Serotonin. So How Do Antidepressants Work? In 2001, a now classic Zoloft commercial hit the airwaves—featuring a sad little blob with a rain cloud following it around. The commercial explains that “while the cause is unknown, depression may be related to an imbalance of natural chemicals between nerve cells in the brain. Prescription Zoloft works to correct this imbalance.” That theory of depression as a chemical imbalance is based on a simple premise: Depressed people’s brains lack serotonin. If a patient takes a serotonin reuptake inhibitor (SSRI), like Prozac or Zoloft, it boosts their serotonin levels, and their depression lifts. The trouble is that when researchers started testing this theory they found it didn’t hold up. Serotonin is certainly involved in depression. But it’s way more complicated than it originally seemed.To be clear, there is a body of research showing that antidepressants do work—it’s just unclear exactly how they work. Read the rest at sciencefriday.com. Understanding Metabolism Genes Might Improve Depression Treatment Sometimes finding the right antidepressant medication is basically trial and error. Scientists are still trying to figure out why some antidepressants work for some people, but not others. Researchers at the Veterans Administration wanted to know if genetic testing might help doctors with prescribing the antidepressant best suited for their patients. Specifically, they examined genes that indicate whether or not someone is able to properly metabolize a medication. Ira is joined by Dr. David Oslin, professor of psychiatry at the Crescenz Department of Veterans Affairs Medical Center and University of Pennsylvania Perelman School of Medicine, to explain his latest research and its broader implications.   Transcripts for each segment will be available the week after the show airs on sciencefriday.com.   Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Ira Flato. Earlier this week, the founder and owner of Patagonia, Yvonne Schenard, you know, that company known for their famous puffer jackets and outdoor gear. Well, he gave away the whole company. Who did he give it to? Well, the Earth, so to speak. Here to tell us more about this surprising news and other science stories of the week is Perbita Saha, deputy editor of Popular Science, based in New York.

Welcome back to Science Friday. Hi, good beautiful afternoon, everyone. So the founder of Patagonia gives away his entire company, right, valued at $3 billion. Where did the money go? Yeah, this is a pretty special case. Unlike other business owners or philanthropists, Yvonne Schenard didn't just donate all his money. He actually took his family's shares in the company and divided it among two organizations. A smaller slice is going to the Patagonia Purpose Trust, which is going to advise decisions on how the

company's profits are spent, again, for the greater good of the earth. And then the lion's share is going to a new nonprofit called the Holdfast Collective. This nonprofit, like I said, is extremely new, but the purpose is supposed to be to protect land and natural resources. And so how is this different from how other billionaires donate their wealth? Billionaires and millionaires. They will do their annual donations, sometimes whether it be to a nonprofit or to a university or even to a trust. But they'll do a lump sum at a time. The way that Von Schenard is giving away his entire company rather than selling it to another business owner

and taking a bit of the profits and donating that toward a climate change initiative. This is just pretty unprecedented. There have been other business owners who've given away their companies to philanthropic organizations, but the way he's doing it specifically for environmental action, a lot of experts are saying that's just completely new. Amazing. That is some nice climate crisis leadership. Let's move on to health news. COVID boosters and flu shots are rolling out again. It's that season. Perbita, is it okay to get both shots at the same time? I was wondering that as I sat getting my booster.

Yes, yes, it is. This has been a burning question, both in my personal circles and in the medical community. A lot of infectious disease experts and even the CDC itself have said it's totally safe to get both at the same time. This is particularly relevant right now with the new Omicron-specific boosters that have just become available and us going into flu season. You don't have to get them both at the same time. The best time to actually get the flu shot or the nasal spray would probably be in October because peak flu season is between December and February. So if you get it next month, your immune system will really be primed to when the virus hits hard. We know this is the new bivalent COVID vaccine, but is there anything new about this flu vaccine? The flu vaccine gets updated every year. The World Health Organization

meets in February to decide what the dominant flu strains are going to be for the upcoming season. And when they decide that, and it's usually different geographically, they make recommendations for how the vaccine should be customized to best protect us. There's talk about the COVID booster being distributed similarly to the flu vaccine like once a year. What's new there? Can we expect that to happen? That seems to still be the prevalent thinking. Anthony Fauci and several other government health experts have said as long as COVID keeps evolving, this is probably going to be the trend. Gregory Pullen from the Mayo Clinic told CNN's Brenda Goodman, our great-great-grandchildren will be getting coronavirus vaccines. So it really is in the same

pattern of the flu vaccine as we see it right now. Interesting, interesting. There's also news on the cancer front, right, a blood test that could help catch cancer earlier. This really sounds promising. Tell us about it. Yeah, so there are a few of these tests in the works, but this is one of the largest scale studies on the results of these tests that we've seen so far. This test is called Gallery, and it's made by the biotech company Grail. It sounds pretty simple. It takes a blood sample, and it looks for biological imprints of cancer activity. And one of the biggest clues is little snippets of DNA that have been mutated or taken over by cancer. The company says that it can detect more than 50 different types of cancer.

Wow. This first study was able to detect 36 different kinds. And some of those are as dire as ovarian and pancreatic cancer, and some are also more blood-specific. And so, of course, we always want to know what are the next steps for this blood test, how soon should we expect to see it in our hospitals or pharmacies? Yeah, so this first round of results was pretty beefy. They tested it on more than 6,000 people.

Out of that pool, 1% of people had early signs of cancer. Out of that 1%, 38% did actually have some different forms of cancer. The other strong finding with this test was that out of the 99% who didn't have cancer, that accuracy level was very, very high. We're hoping to not see false positives out of this test. But this is still very much in the testing phase across multiple hospitals and institutions in the U.S. Yeah, yeah. And our next story takes us into orbit.

This is to the International Space Station where astronauts took photos of Earth at night, not just because they're pretty pictures, but they were doing it for science. Tell us about that, please. Yeah, so being on the International Space Station must be so fun. I mean, I know it's hard. I know there's a lot of work that goes into it. At least for the past few years, the astronauts and cosmonauts on there have been taking daily pictures of Earth. So these photos provide ample data for other scientists down here on Earth. And one pretty unique study that just came out, some scientists looked at the photos taken from the ISS between 20,000. 2012 and 2013, and then 2014 and 2020. And they were specifically looking at the shift in visible light over the European continent. They wanted to track how the trend from incandescent bulbs to LED lights, how that was having a larger effect over the environment and how visible that was, not just here on Earth, but from space. To our eyes, it looks like yellow light from the

incandescent bulbs and white light from the LED lights. But in scientific terms, it's called blue light. Yeah, yeah. And we all know that blue light is not so great for our sleep and our eyesight and stuff like that. Yeah, there are some major concerns that this can disrupt our sleep patterns. Blue light might trick our brains into thinking that it's still day outside. And that, in turn, would stop the production of melanin, which is what makes us sleepy. There isn't a lot of strong evidence on whether this is really a health concern.

Most of it's anecdotal. But it is something that's talked about a lot, especially with things like phone and laptop screens. Now, let's move into some more exciting space news. We have a very cool experiment to look forward to in space. The DART mission, and this is crashing a spacecraft into an asteroid. Wow. Sounds like something out of a movie, Prabita. I think it kind of is.

I mean, I know it's a little corny at this point, but if you've seen the movie, look up, this is exactly what we need to get ahead of problems like asteroids crashing into Earth. But yeah, this is what NASA says is the world's first space defense test system. And essentially, it's just a little, little spacecraft that was sent up into the solar system back in November. It's on track to hit a small asteroid called dimorphus just later this month. It's happening. It's happening soon. Wow. The idea is to knock it off its present orbit to see if we can influence any asteroid in the future that might be heading our way. Yes, exactly. So this is all going to help us understand what kind of physics would go into a collision like this, how much force we need to hit an asteroid

with what can actually be effective. So Dart is really going to be all comprehensive and trying to get a basic understanding of what happens when I like to say you punch an asteroid. Well, let's hope it doesn't turn into that movie because there's really not much chance of that happening, right? Not really. We have constant eyes on the skies

and are always tracking different meteors. Anytime there's even a bit of space debris, toward Earth. Again, there are multiple satellites and cameras checking on its trajectory like minute by minute. Right. All right. Final story, a really interesting one. I understand there's a battle raging in Australia between humans and fierce contenders, the sulfur-crested cockatos. What are they fighting about? Oh, my God. I love these birds. There are people living in the suburbs of Sydney who the cockatoos are just a pest to them because they'll put their trash out on the curb and the cockatoos have figured out a way or multiple ways to lift the lids up and get

into the trash both to pillage it for food but also they seem to just be nefarious and wanting to just leave trash all over the yard and the streets and such. So it's become a real nuisance And this has all happened just in the past few years. The cockatoos have picked up the skill and kept adapting it and even teaching it to others in their little flocks. Wow, that sounds like the raccoons in my yard. So this is interesting from the fact that this is a new thing and they teach it to one another. Yes, exactly. And the authors of the study have even called it an arms race between different species.

So the residents of these areas around Sydney have tried different ways to throw the cockatoos off the trash. So they've weighed the lids down with rocks and water bottles and even put little locks on them. And the cockatoos figure it out. And once they see one cockatoo get through, the others will learn and pick it up. Well, my money is on the cockatoo's. Same here. Same here. As long as the bears around me don't get as smart, I'm happy to watch from afar.

Yes, I agree. Thank you, Perbita, for taking time to be with us today. Thank you. Had a lot of fun. Prabita Saha is the deputy editor of Popular Science based in New York. Break time when we come back. How do antidepressant drugs work or don't work? We're really not sure.

We'll talk about it after the break. This is Science Friday. I'm Iroflato. A quick programming note. Our September Book Club is halfway through, but there's still more ways to participate. You can join us in person in New York City or via live stream next Wednesday, September 21st. We're hosting a lively conversation about Vigina Obscura by Rachel E. Gross. Find out more and buy your ticket on our website, ScienceFriiday.com slash book club.

That's sciencefriiday.com slash book club. And for the rest of this hour, we're going to be talking. about antidepressants. About 13% of adults in the U.S. take them every day. And we're going to dig into what we do and don't know about how they affect the brain and how scientists are working to improve pharmaceutical treatments for depression. Let me start off by asking you, if you remember this commercial from the early 2000s, there's that little sad blob with a rain cloud following it around. While the cause is unknown. Depression may be related to an imbalance of natural chemicals between nerve cells in the brain.

Prescription Zoloft works to correct this imbalance. Anti-depression medication was and is still a Madison Avenue staple. Just ask your doctor. That theory of depression as a chemical imbalance is based on a simple premise. Depressed people's brains lacked serotonin. Give them an SSRI or a serotonin re-uptake inhibitor like Prozac or Zoloft. and serotonin increases, depression lifts. Trouble is when researchers started testing this theory, they found it didn't hold up.

Serotonin is involved in depression, but it's way more complicated than it originally seemed. To be clear, there is a body of research showing that antidepressants do work. We just don't know exactly how. A few months ago, a study was released which summarized decades of research, debunking this over a simplistic chemical imbalance model, which left many research in the field yawning. Hey, we already knew this wasn't true. But this study revealed that the public understanding of depression and antidepressants hasn't kept up with the pace of scientific research.

Joining me now to break down what we do and don't know about how antidepressants work and the future of medication treatment for depression is my guest, Dr. David Hillerstein, Professor of Clinical Psychiatry at Columbia University in New York. Welcome to Science Friday. Ira, thank you for having me. Nice to have you. Okay, let's start off. Can you briefly explain how this chemical imbalance theory came to be?

You know, I think it was an understandable early way of trying to summarize the effect of antidepressants. And it came out first when the tricyclic antidepressants were introduced. in the 1950s and 60s, and they blocked the re-uptake of some chemicals, serotonin and norpinephrine, particularly. And so a very simple way of thinking of that is, well, if it blocks the re-uptake, it must make more of these chemicals available in the brain, and therefore it's kind of logical to think maybe you just didn't have enough. The gas tank was empty. You're filling it up a bit. End of story. So that theory was a way to explain how antidepressants worked after the fact, right, not an understanding of brain chemistry that led to antidepressants.

Right. And I think when the SSRI medications came out in the late 1980s, it was probably a pretty simple marketing message, and it resonated with people. Remember the book, listening to Prozac, wow, it increases your serotonin and gets your depression, your panic, your anxiety better, and so on. Wonderful. And it was a wonderful profit maker for the pharmaceutical company. I think that's an understatement. Anyone who's taken an antidepressant can tell you that they don't work immediately. What can this lag time help us better understand about how they work?

So, right, the antidepressants increase the serotonin available pretty immediately because they block the re-uptake. Yet the effect takes several weeks to appear. So that is the question, why is that? And that's led to a lot of complexity. There are so immediate effects of the medication, but the benefit takes a while to kick in. And so something happens in the brain that is a delayed process and clearly is much more complicated than just filling the tank with gas. So what are some of the alternative theories as to how antidepressants were?

So it's interesting because the article that came out a couple months ago was making a very strong point as though the serotonin deficiency model was still what everybody believes. But it's not. So I think that the reigning theory right now is a chronic stress model. And that chronic stress and vulnerability, because some people have more risk for depression or anxiety or PTSD, chronic stress causes, changes in the brain that are very difficult to undo except with some kind of treatment. So the brain becomes actually shrunken, the size of the brain decreases, the number of synapses, connections between brain cells decreases, and the presence or availability of brain growth factors decreases as well. So the brain is basically injured in the state of depression or anxiety disorders. And therefore, the treatments that we use to the degree that they're effective actually have an impact on the brain structure, connectivity, brain health factors, and brain connectivity. So serotonin and reuptake inhibitors and other antidepressants actually do have an impact on this,

It takes a while for that to happen. And another theory. What other theories are there? Well, so there's an interesting other theory, which is sort of a bias theory, cognitive bias theory. So remember people say, you know, when someone's depressed, they see that the glass is half empty. Right. And not only half empty, but the glass is cracked, right? So everything looks bad and there seems like there's no way to repair it.

So the antidepressants, interestingly, seem to change this cognitive bias in a positive direction. That seems to happen actually pretty quickly. So within the first few days, the someone starts an antidepressant, their negative cognitive bias, their pessimism, hopelessness seems to change even before their mood. improve. So that's an alternative theory is that the antidepressants change this bias, and that enables the brain to start to recover from depression. Is there any evidence that that talk therapy also might have the same kind of effect? So sure, the cognitive behavioral therapy is one of the evidence-based treatments for depression, and actually tackles the negative bias, the sort of pessimism and hopelessness pretty directly. And that has been shown to work clinically. It helps

people and also to have a positive impact on brain connections and activity. So that's kind of the other way to access these types of system. Now, I was surprised to find out that serotonin is not only found in the brain, but is found in other parts of the body, like the gut? Right. So I don't know if you took an embryology course at some point in high school or college, but if you think back way, way long ago, the fetus grows out of three different layers, ectoderm, endoderm, and mesoderm, and the brain and the gut and a bunch of other tissue skin

are formed from ectoderm. So there are receptors that are present in many, many tissues. besides the brain. So the serotonin receptors are present in the gut, they're present in the skin. Someone who's embarrassed will have a rash or a hive sometimes or they'll flush because they have receptors in the skin that are similar to the emotion responsiveness in the brain. Or your stomach. Somebody, you know, you're upset and you're nervous while you feel it in your stomach. You know, irritable bowel classically is something that comes along with anxiety. you know, SSRI antidepressant medicines have some benefit for irritable bowel.

So this might explain why SSRIs can work for other disorders. Such as pain would be another example, right. Yeah. A lot of folks may be listening to this and saying to themselves, wow, if the scientists don't even fully understand how antidepressants work, maybe I should think about not taking them anymore, just going cold turkey off my antidepressants. That's not a great idea, is it?

No, definitely not. And I would say one kind of metaphor to think about is, you know, if you have a strep throat and your doctor prescribes a penicillin or ampicillin, you need that to get better from your strep throat. It doesn't mean the strep throat comes from a penicillin deficiency. Hmm, that's interesting. I want to talk a bit about the latest in depression drug research. And a lot of what we're hearing these days is successful.

success with psychedelic, psilocybin, ketamines. For example, the FDA recently approved the use of a drug similar to ketamine for depression resistant to other treatments. This is a cutting edge area, isn't it? Absolutely. One of the frontiers with depression treatment is trying to find rapid treatments that will affect the brain networks, connections, transmitters in a matter of hours or days rather than weeks or months. And so ketamine, a single dose of ketamine, can have a major impact on brain, chemistry, and mood. And we're part of some psilocybin studies here at Columbia. And the first large study was just completed and is about to be reported.

And it looks like it's pretty successful at having a single dose of psilocybin, helping a significant number of people with treatment resistant depression, works within a couple of days. The effects last for most people for three weeks and then up to 12 weeks. And so it's really, we understand a lot more about depression, but the frontier is how do we get rapid onset of benefit? And then how do we keep it? Because ketamine, people get out of the depression,

but we haven't really figured out how to keep them non-depressed the best possible way. So it's not resetting something in the brain? Is it doing something to brain circuitry? Yeah, so psilocybin, for example, causes massive changes in brain activity. Parts of the brain talk to each other that don't normally talk to each other. You know, people would hear colors, see sounds, talk to God, you know, see the beginning and end of the university's kind of extreme experiences because their brain circuits are firing off in a pretty intense kind of Fourth of July way. and then the days and weeks following the treatment, it looks like the reorganization of brain network. So one of the things that seems to happen for a lot of people with depression is kind of a broken record,

for those of us remember record players. You know, you get a groove worn into a record which plays the same couple of notes over and over again. And the rapid acting treatments, it's thought can get people out of those kind of broken record cycles and help reconnect the brain in new ways. And there's evidence that these drugs increase plasticity or the ability of the adult brain to kind of reconnect and regrow connections. Did I hear you say, though, that it's not a lasting effect? Well, ketamine has a short-acting effect, and then when you get the person out of the depression with ketamine, you have to figure out how to keep them out of the depression. So it doesn't necessarily totally go away. It's just that you give them kind of a boost out of

the depression and then they you need to find the best ways to maintain that with psilocybin most of the studies the first studies were doing two dosings the current studies are just doing one dosing and the question's going to be is that enough for some people it seems to be other people might need two doses and then how do you maintain the the improvement after that so it's not a a slam dunk boom you're better forever, it's more of a jolt, you're out of the state, and then how do you make the most of it? Right. You could be put on maintenance doses. And actually, yes. And actually the other thing that's really interesting is how do you best combine that with psychotherapy? Because if the brain is now more fluid, its connections are

restructuring themselves or reconnecting, maybe that's a time for enhanced learning and for people to find ways to reconnect with their activities, interests, other people, and to kind of break the broken record cycles. This is Science Friday from WNYC Studios. If you're just joining us, we're talking with Dr. David Hellenstein, professor of clinical psychiatry at Columbia University, talking about what we know and don't know about how antidepressants work. When do you think that this newer type, these newer types of drugs might replace SSRIs. You know, millions of people around the world take these drugs every day. Well, the psychedelic drugs are just about to start phase three studies.

So it's going to be a couple of years before they're FDA approved, assuming that that happens. And they're very labor intensive. So it's going to be hard to scale up lots of treatments for lots of people. And so that's going to be an ongoing challenge to figure out how to get, if, if they're really as good as people think, which has to be actually proven, then it's going to be a real process to figure out how to get them out to people. Maybe psychedelic types of drugs, but that don't give a trip, that's one alternative that might be actually, sounds kind of contradictory or impossible, but the drugs that affect the same receptors that don't give a trip, that might be an alternative that might not be so labor intensive. Do you think that the pharmaceutical companies are going to push back against this? because they're making so much money on these SSRIs?

I think the boat of SSRIs has sailed. Actually, the big drug companies have disinvested from psychiatric research. I really wish they would get back into the business because we need better drugs and new drugs, not just the psychedelics and the ketamines, but we need a lot of treatments that are more effective. And really, the new wave of psychedelic and ketamine studies is being funded mostly by small startup companies.

Well, they could become big companies. Could they not? I mean? They could or they, you know, it's an interesting question. I'm not a business person, but sometimes they get acquired. That kind of thing tends to happen. But this is an optimistic future from what I'm hearing you say. You know, I think that, you know, we've gotten out of the sort of lockbox of the serotonin deficiency model.

We think serotonin is involved with depression in a complicated way, but it's not just, here's what we do. We fill the gas with serotonin, and that's the end of the story. We see a complicated system, but one that may have possible places to make an impact that could be rapid and onset and could have a significant impact. So I think it's really, we're actually a very exciting period right now. Great to hear that, Dr. Hellerstein. Thank you for taking to have to be with us today. Ira, thank you so much for having me. You're welcome.

Dr. David Hellenstein, professor of clinical psychiatry at Columbia University in New York. We have to take a quick break, and when we come back, we'll continue our conversation about antidepressants. Can genetic testing help doctors find the medication best suited for their individual patients? A critical issue for us in the psychiatry field is not necessarily knowing which medicine is going to work. with which patient. You know, we'll try what we think is a good standard medicine in somebody, but if that doesn't work, we'll need to move on to another. Stay with us. This is Science Friday. I'm Ira Flato. We're continuing our conversation about what we do and don't know about how

antidepressants work. Sometimes finding the right medication is basically trial and error, and that's because scientists are still trying to figure out why some antidepressants work for some people, but not for others. Researchers at the Veterans Administration wanted to know if genetic testing might help doctors with prescribing the antidepressant best suited for their patients. Specifically, they looked at genes that indicate whether or not someone is able to properly metabolize a medication. Joining me to explain this research and its broader implications is my guest, Dr. David Oslin, Professor of Psychiatry at the Cresens Department of Veterans Affairs Medical Center, University of Pennsylvania, Perlman's School of Medicine based in Philadelphia, PA. Welcome to Science Friday.

Thanks, Ira. It's great to be here today with you. Thank you. Let's start off by talking about why did you decide to test for these specific genes linked to metabolism? As you outlined in the beginning, a critical issue for us in the psychiatry field is not necessarily knowing which medicine is going to work with which patient. And that often leads to this trial and error kind of approach where, you know, we'll try what we think is a good standard medicine in somebody, but if that doesn't work, we'll need to move on to another. Sometimes we're lucky in that first one works quite well, but often not. So there's a lot of factors that go into that decisional process. And a factor that we have known about for a number of years is variability and metabolism

that is dictated by your genes. And so there are a number of companies now that offered genetic testing or pharmacogenetic testing that helps us better understand how you metabolize antidepressants or even other medicines. And the goal of our project was to see if that actually helped treat patients or lead to better outcomes for patients. And did it? Well, the short answer is yes, but it's a little bit more complicated than that. So a big piece of genetics is that the genetic test for a given medicine probably don't tell us an answer for every patient.

And the way to think about that in the study that we published was that in the control group, which did not have the pharmacogenetic testing, at the end of the day, about 20% of them ended up getting put on a medicine where genetic testing would have told us that we probably should have selected something different. The other 80% did not have a drug gene interaction. So the test was really mostly helpful for that 20% and we have to know that limitation sort of going into it. And so you then adjust for that limitation? So our design didn't let us adjust for that. So we're going to do some further analyses and explore that issue.

Even with the fact that the genetic test was only likely relevant for about 20%, we saw a positive difference. The way this study was designed was it's a typical randomized clinical trial where patients were randomly assigned to, in this case, getting back a gene test, test results that helped them and their provider work on which medicine they wanted to use in the treatment of the depression, or they didn't get a test result back, and they were treated as usual. And in the treatment with the genetic test group, over the course of six months, the patients did better. They did better in terms of the percentage of patients that ended up in remission,

as well as the patients that just responded to some extent. Yeah. I know that you were initially. skeptical that this approach might be useful until you did this research. Why is that? So, yes, I was skeptical going into this because my clinical experience is that these medications have a fairly broad therapeutic index, meaning I don't have to get the dose exactly right for them to be effective. And we've never really had literature that says that serum drug levels are really good at predicting outcomes. So the idea that metabolism might make a difference just didn't have a lot of scientific background in a lot of ways. So I've been pleasantly surprised

that it's made a difference in the patients that we enrolled in the study. Is it possible to figure out why that percentage of 20% of the patients found success and the others didn't? So that's a great question. It wasn't necessarily that that 20% found success. Lots of patients found success. The study wasn't designed to tease out who the 20% are. So what the 20% reflects is in the control condition, 20% of those patients ended up being started on a medicine that had a drug gene interaction. But those providers and patients didn't have that gene result to steer them in another direction. Overall, the difference in outcomes was about 5 to 10 percent different. So about 5 to 10 percent more patients remitted over the course of six months than in the usual care group. So what does this tell you? What do you learn from this and how do the patients benefit from what you've learned? What I think of this area of medicine is being in sort of its infancy.

these particular tests that are available now are really a first generation of genetic tests for us. We really like to have tests that really predict which medicine is going to work better for which person, and that's not what these tests do. So I think this is a really good step forward. I think in my practice I'll probably be using these tests more often, probably not in every patient, but certainly in more patients than what we were using before. And I feel like we're moving the field forward to a time where we don't have to have quite as much trial and error with these medications.

Will they help you choose which medicines to give your patients, even though we're talking about this 20%? In the world of antidepressants, we have a number of options, none of which really work any better than the other. So if I have one that I don't know how to dose well, I can pick another that's not genetically influenced and otherwise equal in terms of its chance of helping that person. And that should lead to better outcomes and did in the study. That's interesting. What about uses to help those who are taking multiple psychotropic medications? Right there are a lot of people who do this.

Might have helped determine how well patients are actually absorbing the drugs. and if they can reduce the amount of medications that are not working? We don't have the answer to that. It's an area that I'm particularly interested in. So in medicine these days, we often add more medicines when something's not working, particularly with chronic illnesses like depression. So if I start you on treatment X and you get some response to it, but not a full response to that treatment,

I'm more likely to add something else, on to the regimen to see if I can boost that response. So people end up on lots of medicines. So, and that's the unfortunate part of that practice. So the idea of genetics could be that some of those medicines just shouldn't have been good mixes or matches for that patient. And if I have a genetic test that suggests that a medicine is poorly metabolized or rapidly metabolized, maybe taking that one away.

and swapping it out or just taking it away could actually lead to a better outcome for that patient. You know, some people may be confusing this with genetic testing for, let's say, cancer screening, something like that, where you're actually determining whether the drug works. This is not what you're doing, right? That's correct. So the cancer field is much further ahead than we are in the mental health field with how to use genetics and practice. a good example might be the broca gene for breast cancer, where if you have a particular mutation in the cancer, it's actually going to dictate which treatment you get. Here we're really, again,

sort of in our infancy of applying genetics to the treatment of mental health, and really talking about how people metabolize the medication, which will have a fact. So as an example, if I am an ultra-rapid metabolizer of a particular antidepressant, I might end up at a standard dose with a much lower serum level of that medicine than will be effective. On the other end of the spectrum, I could be a slow metabolizer, and I will actually end up with a much higher dose than what's prescribed. And most of our medications, adverse events are dose response related, and so I'm more likely to have side effects or adverse events from that medicine from a slow metabolizer. You know, there are very few diseases where one gene controls, right, the disease, very few of them.

And I think people are probably expecting to find maybe the genetic underpinnings of depression, but that may not turn out to be the way it really works, right? Yeah, so most chronic illnesses are probably not one disorder. even simple disorders like hypertension, high blood pressure, really aren't one disease. There are really likely many different diseases that have different pathways that manifest themselves in an elevated blood pressure. Depression's the same way. Some patients have depression that's really driven by biology, and those patients might be

much more responsive to an antidepressant or a particular antidepressant. Some people's depression may be much more driven by their environment and their psychosocial circumstances. So we don't have great ways of teasing out those different types of depression right now, and that is the hope for the future. Can the genetic screening tell us what deficiencies patients may have in certain key neurotransmitters? That is sort of the holy grail of trying to tease out some of the different. the depression. So there are some of the commercial products that are on the market that do say that

they can do this. I would say the science is lukewarm on whether those tests are useful or not. And so I think we still have a little ways to go to do there. This is Science Friday from WNYC Studios. Well, let me expand this topic. Can these genes be used to help figure out how well someone can metabolize other types of medications, not just antidepressants. Yeah, so that's actually another very important point. The reality is that these metabolic genes really tell us how well the liver works in general. These are all genes that are that help the liver perform well, and they're pretty agnostic to the medication. So any medication that is metabolized by the liver can be affected by these genes. And that's a real varied number of

medications, cardiovascular medicines, medications for infections, medications for GI problems, et cetera. You know, some people are listening at home and they might be thinking, as I, the question I was thinking, you know, you can buy these home genetic testing services, right? Can those services tell us how well I'm metabolizing my antidepressants? Some of the commercial firms that advertised to patients directly or to people directly do include some of these metabolic genes in their panel and do report back to you. I really think that that's a conversation that you should be having with your health care provider, though, in terms of interpreting those genes and understanding which medicines those genes may be influencing. I would hate for somebody to

stop a medicine that's been working effectively just because they did a, a home test. Right. Right. So are you actually using any of these tests on your patients at the VA yet? Yes, we do. We actually have available a couple different options for providers to order the test. And we do get both patients that are interested, but also providers that use the test in helping them select the medications, not just in psychiatry, but again, across a broad array of disorders. Yeah, because you stopped to figure out who's best to test. Yeah, that's actually, so that was another learning lesson from the study, and we are trying to do some secondary analysis to see if we could actually better target who to test and who might benefit.

One of the better stories here might be testing people with their first episode of depression and not necessarily their third or fourth medicine. But we have more to work to do in that area. I mean, there's two approaches here. One is you just test everybody. These genetic tests are actually getting really inexpensive to do. And if you think about the cost of a test over somebody's lifetime, it's really not that expensive.

Or the other approach is to target the testing when you think it's most valuable. What about other illnesses? What's next on your research? How can you apply this to others? So I'm a psychiatrist, and I'm mostly interested. in mental health disorders. So we are trying to think about how to combine genetic testing with other useful techniques to target treatment. So in our group, we're looking at neurocognition as a way to think about who might benefit best from different forms of psychotherapy. We're

interested in PTSD and how to improve outcomes from PTSD. And there's a lot of applications here about how to do a better job of having what we call precision mental health care. Yeah, that really is a challenge, isn't it? I think it's a challenge, but it's really exciting. I mean, I think a lot of people think of mental health as this black box of only sitting down and lying on the couch and talking things out. But we really do have a lot of different evidence-based approaches to treating different illnesses. And the challenge these days for me is really figuring out which one's going to work best for which patient. Thank you, Dr. Osslin, for taking care.

time to be with us today. Thank you, Ira. Dr. David Oslin, Professor of Psychiatry at the Cresens Department of Veterans Affairs Medical Center. That's at the famous University of Pennsylvania P.lman School of Medicine, based in Philadelphia, PA. One more thing before we go. I want to note the passing of public radio pioneer and colleague Jim Russell. As one of the original reporters for all things considered, he crafted the art of radio storytelling of the kind that's common today. If you listen to Marketplace, that was his creation, too. He also helped develop Morning Edition and PRIs the world. Moving to PBS, Jim hired me as host

of Newton's Apple and worked with me in shepherding Science Friday through our early NPR years. Jim was never afraid to speak out and remind us of our public mission. He was a staunch defender of the integrity of the job we do. As a lifelong friend and colleague, Jim Russell, will be missed. Condolences to all whom he touched. And that's about all the time we have for this hour. Here's Ariel Zitch with some of the folks who helped make this show happen. Thanks, Ira. Charles Berkwist is our radio director. Sandy Roberts is our education program manager. Danielle Dana is our executive director, and I'm Director of Audience, Ariel Zich. Thanks for listening. Thank you, Ariel. BJ Leiterman composed our theme music, and of course, if you missed any part of the program or you'd like to hear it again, subscribe to our podcasts, or ask your smart speaker to play Science Friday. And if you prefer, you can always email us, yes, SciFri at ScienceFri.com. Have a great weekend. I'm Ira Flato.