Clinicians are inundated with ads for genetic testing, but is genetic testing currently helpful for informing clinical care? The latest issue of The Carlat Child Psychiatry Report includes an interview with Dr. Aaron Besterman, who’s an adult and child & adolescent psychiatrist at the Rady Children’s Hospital inpatient child and adolescent unit in San Diego. He also conducts psychiatric genetic research as a clinical investigator at the Rady Children’s Institute for Genomic Medicine. In our interview with Dr. Besterman, he broke down the current state of genetic research in psychiatry, explaining how these genetic tests work, and what can be reliably taken away from them. Mara and I will discuss the highlights from our interview with Dr. Besterman in this episode.
Published On: 6/7/2021
Duration: 22 minutes, 4 seconds
Related Article: "Pharmacogenetics: Not Quite Ready for Prime Time?" The Carlat Child Psychiatry Report, January/February/March 2021
Welcome to The Carlat Psychiatry Podcast.
This is a special episode from the child psychiatry team.
I’m Dr. Josh Feder, The Editor-in-Chief of The Carlat Child Psychiatry Report and co-author of The Child Medication Fact Book for Psychiatric Practice.
Mara: And I’m Mara Goverman, a Licensed Clinical Social Worker in Southern California with a private practice.
I’m also a regional director at Positive Development Institute.
Dr. Feder: Genetic testing is a very complicated landscape. And Dr. Besterman expressed that there’s one really important distinction that clinicians should be aware of. It’s the difference between the two types of genetic tests available.
(Dr. Besterman Response)
Dr. Feder: Studies have shown that, in 10%–20% of patients with neurodevelopmental disorders, CMA can detect a change associated with a specific genetic syndrome. It’s also recommended that boys get testing to look for Fragile X syndrome.
Mara: Dr. Besterman mentioned that diagnostic testing doesn’t significantly alter psychiatric care, and that’s important for patients and families to know. But it can be useful in a number of other ways.
Dr. Feder: For example, it can inform providers about the need to monitor for common comorbidities with some genetic conditions. It can also provide families with an answer for why their child has a certain condition, which can provide relief to those who’ve been on a diagnostic odyssey, going from specialist to specialist looking for an answer.
Mara: It can help families connect with other families who have a child with a similar genetic condition for social and emotional support. Genetic testing also helps with reproductive counseling, if a family wants to know whether their next child could have the same condition.
Dr. Feder: Lastly, diagnostic testing can plug families into clinical research opportunities where kids could be enrolled in research studies specifically for their genetic condition.
Mara: This is an important point because these large studies can certainly provide families with valuable information about their child. A lot of them are now doing sophisticated genetic testing and the chances of finding a genetic cause for their child’s disorder is increasing.
Dr. Feder: These studies also provide neurobehavioral evaluations that can be helpful for families, too.
Mara: So, we’ve been hearing a lot about polygenic risk and, specifically, there’s a lot of talk about polygenic risk scores. In our interview with Dr. Besterman, we touched on this topic and how it applies to the field of psychiatry.
(Dr. Besterman Response)
Mara: Wow, it seems like polygenic risk scores could have a lot of applications in psychiatry and medicine as a whole. By using these risk scores, can you identify someone at an elevated risk for a psychiatric disorder? Or even detect whether someone will have a disorder before they start having symptoms? And can we use this risk score to predict the future onset of a disease?
Dr. Feder: Unfortunately, with the current state of psychiatric genetic research, we really can’t use polygenic risk scores in our practice.
Mara: According to Dr. Besterman, the risk scores are not good enough yet to predict with any clinical certainty that someone will have one of these psychiatric disorders.
Dr. Feder: The future goal isn’t to necessarily use these risk scores in isolation. The goal is to combine them with other potential risk factors to try to improve our prediction of the onset of a disease. But this is still very much in the research realm and has not been proven to be clinically useful yet.
Mara: Right now these polygenic risk scores, associated with small, little genetic changes, are significantly worse at predicting disease likelihood in minority populations or non-European ancestry populations.
(Dr. Besterman Response)
Dr. Feder: And when it comes down to providing your patients with proper counseling after they’ve received their genetic test results, there are a few different options.
Mara: If you feel comfortable providing counseling on your own, then go for it! The guidelines for genetic testing and genetic education from The International Society of Psychiatric Genetics (ISPG) are a helpful and informative resource. We placed a link to the ISPG guidelines in our latest newsletter.
Dr. Feder: However, there are alternatives. If you’re not fully comfortable with providing counseling, two excellent resources to work alongside are Medical geneticists who are MDs and non-MD genetic counselors.
Mara: Genetic counselors are experts in genetic medicine and often work alongside medical geneticists. They can facilitate genetic testing, consenting for genetic testing, and counseling to accompany test results. And you can find one through the National Society of Genetic Counselors.
Dr. Feder: You can work alongside genetic specialists to make sure patients get what they need. If you order a test and it comes back positive, you could refer the patient to a medical geneticist for further counseling. Even if it comes back negative, you could refer to a geneticist if you feel the patient might benefit from more sophisticated testing.
Mara: Okay, so that’s diagnostic testing. Let's move onto the more controversial type of testing, pharmacogenetic testing.
Dr. Feder: This type of testing looks at a group of genes involved in drug metabolism or involved in how our body responds to drugs and our particular sensitivities to drugs.
(Dr. Besterman Response)
Mara: Okay, to sum it up the CYP2D6, HLA-B, and CYP2C19 genes are the only ones that are recommended in psychiatry. Even though we hear a lot about other ones, like the MTHFR gene and the COMT gene.
Dr. Feder: Yeah, there’s a lot of marketing for those particular genes, especially for the corresponding L-methylfolate supplementation. We asked Dr. Besterman about how these genes got thrown into the mix.
(Dr. Besterman Response)
Mara: That’s not to say that those genes have absolutely no role in the neurobiology of psychiatric illness, but there is insufficient evidence to say testing for changes in those genes will alter our care in any way.
Dr. Feder: There are a lot of direct-to-consumer commercial companies, like the well-known 23andMe, in the world of pharmacogenetics.
Mara: These companies send patients and their doctors a report that puts medications in green, yellow, and red boxes. But how they come to those conclusions is not well understood.
Dr. Feder: Dr. Besterman is apprehensive about utilizing medication recommendations from these companies, and his apprehension is, well, justified.
Mara: If you compare the recommendations between companies, they’re often very inconsistent.
Dr. Feder: There was a study a few years ago by Bousman and colleagues. They took patient samples and sent them to different direct-to-consumer laboratories and compared their specific medication recommendations.
Mara: There was a lot of inconsistency between the companies, not only in the specific genotypes, but also in the metabolic phenotypes — meaning whether they thought a given patient was a poor, intermediate, or rapid metabolizer. And the medications that they were putting into green, yellow, and red boxes were also very different.
Dr. Feder: It’s unclear how these companies arrive at and make their recommendations, which is a big problem caused by the lack of standardization in the field.
Mara: Fortunately, the FDA started sending cease-and-desist letters to some of these companies last year. The field is undergoing some evolution, and that’s probably a healthy thing…
Dr. Besterman cautioned us that the information obtained from pharmacogenetic testing can be very misleading, and can potentially even cause harm.
Dr. Feder: Definitely. I recently saw two patients whose families insisted on getting a pharmacogenetic test to see what medication their child should have. In both cases, I told them I didn’t think the test would tell us anything, and it would be expensive and might even suggest things that aren’t helpful. One family hasn’t done it yet, maybe because of the cost. I had already started the other patient, a teen, on fluoxetine because that’s what the clinical data supported. The kid had a great response to the fluoxetine, but the test report said it was in the “red” box and therefore recommended against using it.
Mara: This is exactly what Dr. Besterman warned us about. Specifically, these tests can drive patients to not use medications that could potentially be helpful, or to stop medications that are already helpful, because families don’t understand what it means for the medication to be in a red box.
Dr. Feder: A lot of patients come to us and say, “I had a relative, they had this pharmacogenetic testing. It showed them why their medication didn’t work. Now they’re on a different medicine, they’re doing great. I want the test, too.”
Personally, I like to stick with the common approach in psychiatry, which is that each individual patient is unique and we really need to sort of assess them individually. So, it’s important to try to really understand what their goal is, and then decide whether pharmacogenetic testing is helpful for that patient.
Mara: And this can be a difficult situation to navigate because it’s comforting to see data supporting which medications will help and which ones won’t. But patients and families should know that pharmacogenetics does not reveal whether someone will respond well to a medication, and since direct-to-consumer companies are not consistent in their recommendations, patient’s should know that these tests shouldn’t be the main component directing our treatment plans.
Dr. Feder: Overall, we are still in the beginning stages of incorporating genetic research into psychiatry.
Mara: As we learn more down the road, we might be able to use diagnostic and pharmacogenetic testing to inform psychiatric care because there are some benefits to them. But, at this very moment, we’re just not ready yet.
Dr. Feder: Our interview with Dr. Besterman was much needed because, frankly, psychiatric genetics is a big and unwieldy field when you think about it.
Mara: From the inconsistencies between direct-to-consumer companies, to the large studies that are only really generalizable and relevant to Caucasians of European descent.
Dr. Feder: And, on top of that, there’s a lot to be aware of when it comes down to which genes can tell you what, and which genes lack the evidence behind them to substantially inform you of anything.
Mara: Nevertheless, there are many beneficial things that we can currently take away from the use of genetic testing in psychiatry.
Dr. Feder: But hopefully, in the future, we can incorporate genetics in psychiatry to an even greater extent, and, ultimately, improve treatment for our patients.
Mara: As a bottom-line message, Dr. Besterman believes that clinicians should learn more about genetics.
(Dr. Besterman Response)
Dr. Feder: There are many resources out there to gain more insight into the world of psychiatric genetics. Dr. Besterman has co-written some reviews regarding what psychiatrists need to know about genetics that are freely available on PubMed, and we’ve posted a link to his reviews in our newsletter.
Mara: In addition to the ISPG, there’s also the National Neuroscience Curriculum Initiative or NNCI, which is an incredible education resource with many online modules that take you step by step through easily digestible scenarios, including genetics.
Dr. Feder: The newsletter interview is available for subscribers to read in The Carlat Child Psychiatry Report. Hopefully people check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits.
Mara: And everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry.
Dr. Feder: Yes, the newsletters and books we depend entirely on reader support. There are no ads and our authors don’t receive industry funding. That helps us bring you unbiased information you can trust.
Mara: Go to www.thecarlatreport.com to sign up. You can get a full subscription to any of our three newsletters for $30 off using the coupon code LISTENER.
There are a lot of doctors and nurse practitioners listening, and quite a few students and residents too. Everyone who responded was interested in getting some kind of CME credit for listening.
Dr. Feder: So we’re going to do it! We’re working on putting that program together now and as soon as it’s available you’ll be able to take a post-test for listening and get credits. Everyone who took the survey is going to get early notification when it’s ready because we have their email address.
If you’d like to get that early notification you can still take the survey at www.thecarlatreport.com/podcastsurvey.
Mara: As always, the links you need are in the episode description. Thanks for listening and have a great day!
- The International Society of Psychiatric Genetics
- National Society of Genetic Counselors
- Clinical Pharmacogenetics Implementation Consortium
- Bousman CA et al, Pharmacogenet Genomics 2017;27(11):387-393
- Reviews co-written by Dr. Besterman
- National Neuroscience Curriculum Initiative
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