Can biology fix how ADHD is diagnosed?

The manual that shapes how mental health conditions are diagnosed is changing. The next edition of the Diagnostic and Statistical Manual of Mental Disorders, or DSM, is set to include biology for the first time.

Right now, diagnosing conditions like ADHD and depression relies on symptoms, self-reports, and a clinician’s judgment, not lab tests. Geriatric psychiatrist Anand Kumar, who until recently served on a strategic committee for the DSM, pushed to change that. The new edition will introduce “biological factors.” These are measurable processes in the body that are linked to a condition but aren’t yet a diagnostic test.

Rae Jacobson asks Anand what this shift could mean for people with ADHD, depression, and more. They talk about more targeted treatment, why there may never be a single test for ADHD, and the risks — including what happens to the people a new test doesn’t capture.

• Read: Anand’s article in The Conversation

• Watch: Do we need a new way to talk about ADHD?

Dr. Anand Kumar: It's the absence of biomarkers that puts psychiatry in a kind of la-la land, okay, where people think this is all made up.

Rae Jacobson: How do you diagnose a disorder you can't see? It's a question psychiatrists have been wrestling with since the dawn of their field.

Right now, for example, a good clinician diagnoses something like depression by ruling out physical causes, asking specific questions, and seeing how the answers match up with a set of criteria laid out in a book called the "Diagnostic and Statistical Manual of Mental Disorders," a.k.a. the "DSM."

The book, which is sometimes called the Bible of psychiatry, gives clinicians a guide for diagnosing and treating basically all psychiatric and neurodevelopmental disorders. It's a pretty good system, but it's not perfect. And with each revision of the "DSM," the team of clinicians who help write and revise it keep looking for ways to improve how we diagnose and treat the disorders it covers.

And in extremely big news, if you follow this kind of stuff, there's a new version of the "DSM" on the way, and a really big question is being asked: What if there were a way to include biology in the Bible of psychiatry? What would that look like, and could it help us make our way to more objective assessments, like blood tests or brain scans, that could give clear answers about diagnosis and treatment?

These things already exist for many, many physical diseases, and they have a name: biomarkers. Tests that are widely used in other fields of medicine to diagnose patients or measure how they're responding to treatment.

Now, I want to be clear, just so we're not all running out to get fMRIs or what have you, as you'll hear, we do not yet have reliable biomarkers for most mental health or neurodevelopmental conditions. But there's a vocal group of scientists who think we do now have enough data to start adding biology to the "DSM," and my guest today is one of them.

Anand: I think it's important to bring biology into the "DSM", as important as it is when we speak of biology in the context of cancer or lung disease or diabetes.

Rae: Dr. Anand Kumar is the head of the Department of Psychiatry at the University of Illinois Chicago. He's a geriatric psychiatrist whose research focuses on things like late-life depression and Alzheimer's. Until recently, he was also part of the strategic committee that's helping to write the new "DSM." And he is, as you will hear, a consummate academic and very, very charming.

Anand: The papers are all strewn all behind me. Should I arrange them or it's okay?

Rae: Honestly, this is a show that people listen who have ADHD, I think they will find it comforting.

Anand: Okay.

Rae: Anand and his colleagues believe biomarkers and other types of biology called biological factors should be added to the new "DSM." They and the many other teams of scientists and clinicians who are working on the new revision debated and consulted and discussed, and Anand's camp won.

It is hard to overstate how big of a deal this is. These discussions can sound kind of remote and academic, but they have a very real impact on millions of people. This manual plays a huge part in defining how patients get diagnosed, how doctors view mental health conditions, and who does and doesn't get services.

So today on "Hyperfocus," Dr. Anand Kumar on this big shift. What are the risks, and what do we stand to gain?

(03:25) Dr. Anand Kumar explains how psychiatry currently defines conditions and why biomarkers are needed.

Anand: The "DSM" comes out about every decade roughly, 10 to 15 years, and because of an absence of clear biological categories or biomarkers as we call them, "DSM" tends to be very descriptive.

Rae: You advocate for bringing them into the "DSM" though.

Anand: Oh, very much so, and there are many people on the committee, when I was part of the committee, who were very much for it. And here are some of the problems.

Rae: Okay.

Anand: The only area of psychiatry, behavioral neuroscience, whatever you want to call it, that has a clear biomarker is Alzheimer's disease. There are two abnormal proteins in the brain. These were first described by Dr. Alzheimer, who was a psychiatrist, over 100 years ago, about 120 years ago.

Rae: I didn't know he was a psychiatrist.

Anand: Yes, a lot of people don't. And the other thing a lot of people are not fully aware is Sigmund Freud was a neurologist.

Rae: You're teaching me many different things today.

Anand: Alzheimer described a case. The patient was someone who was admitted to what was called an asylum for the insane in Frankfurt. After the patient passed — her name was Auguste Deter — her brain was sent to Dr. Alzheimer to be examined.

He described three things: atrophy, the brain had shrunk, and he described two proteins in the brain that were not known at that time: amyloid and tau, two new proteins.

Rae: I'm interested because Alzheimer's, I admit part of the reason that I haven't thought about it — I think a lot of people don't always realize that it's considered a psychiatric disorder — is because it feels, like you say, very different from a lot of the things that I associate in the "DSM".

Anand: Yes.

Rae: Which, we don't have biomarkers for these. You couldn't give me a blood test and tell if I have depression, ADHD, or anxiety, correct?

Anand: Exactly. Unlike the rest of psychiatry, Alzheimer's has — we have biomarkers. About a year and a half ago, the FDA approved the first blood test for Alzheimer's.

Rae: Wow.

Anand: Now you can study amyloid and tau by getting a simple blood sample. The rest of psychiatry, as you pointed out, depression, schizophrenia, eating disorders, anxiety disorders, there is no clinically valid biomarker today. There are interesting findings from research, but which today cannot be applied easily in a clinical setting.

Rae: One of the reasons I was so curious to talk to you today, and one of the things that comes up for us in our work, is people will frequently say, "Well, you know, there's no biomarker for ADHD, so do we really think it's real?"

And I'm wondering if the fact that there are biomarkers for Alzheimer's put it in kind of like a different mental space for people who are approaching this, and sort of what the implications of that would be for these other conditions that don't necessarily have that easy-to-touch validity.

Anand: Right. You hit the nail on the head. You see, absence of biomarkers, which reflects an absence of a clear pathophysiological or biological explanation for these disorders, that puts psychiatry — I want to pick my words here — in a kind of la-la land, okay, where people think this is all made up.

A bunch of psychiatrists get into a room, decide what's a disease, what's not a disease, and that is not correct. I would respond by saying absence of clear-cut biomarkers doesn't mean these conditions don't have significant impact in the lives of patients.

You spoke of ADHD, that's one. Bipolar disorder, schizophrenia, anxiety disorder, panic disorder, PTSD, phobias, eating disorders, and on and on and on. Absence of biological clarity doesn't mean these are not valid conditions.

(07:23) Biological factors can offer meaningful context for psychiatric diagnosis even without simple biomarkers.

Rae: Now, you might be wondering, if there are almost no biomarkers at all, what are we even talking about here? Well, Anand says that even without perfect blood tests, biology is still important. It can offer context that might be helpful for clinicians.

This isn't a revolutionary idea. He says that other branches of medicine are much more open to recognizing that there can be multiple types of risk factors for a disease, some biological and some environmental. And while biological risk factors can be very useful, they're not the be-all and end-all. Instead, they're part of a bigger picture.

Anand: So let me give you a couple of examples. So, lung cancer: You can get lung cancer without ever being a smoker, but many cases of lung cancer are associated with smoking and a genetic risk.

Cardiovascular disease: There are risk factors — no single gene, but multiple genetic risk factors for cardiovascular disease. But cardiovascular disease, heart attack being the most notable, also has environmental factors: diet, lack of exercise, high BMI meaning obesity.

But in the field of clinical cardiology, the concept that genetics contributes substantial risk, but so do environmental factors, are widely understood and accepted. And I think it's important to bring biology into the "DSM", as important as it is when we speak of biology in the context of cancer or lung disease or diabetes, heart disease.

Rae: Why hasn't biology been included in the "DSM" before?

Anand: For one simple reason: There are no clear-cut, easily identifiable biomarkers. Even those who are enthusiastic about talking about biology are cautious about prematurely saying, "Oh, we have a blood test for whatever," and then that not working out.

Rae: So they've looked, but they've been hard to find.

Anand: Yes. And they've made one or two mistakes 20, 30 years ago. In retrospect, the findings were real, but it was oversold as a blood test, and consequently, in my view, people are gun-shy.

Rae: When Anand says people are "gun-shy," he means people who work in the psychiatric field, his colleagues. And if you've ever asked any doctor anything, this won't surprise you. Doctors want to be sure if they say, "This works," whatever it is actually works.

Because if it doesn't, the consequences can be really serious. A person could get the wrong diagnosis, the wrong treatment, or get hurt. And when things do fail, it erodes public trust. So, while it's not hard to see why people in his field might be hesitant, Anand thinks we may have swung too far in the other direction.

Anand: I would go to the extent of — and this is provocative language — to say that there's some degree of neuroscience phobia within the clinical community and the psychiatric community. The gap — and I'm sticking my neck out here — but the gap between research and practice is greater in psychiatry than it is in many other branches of medicine.

And the explanation that one is often offered, which is the correct one, is that these are very complex diseases. Not that cancer isn't, not that diabetes isn't, this is arguably even more complicated. That's because of the complexity of the brain. That's because of the complexity of — many of these "DSM" categories are syndromes, meaning they are not just one disease, but multiple diseases that share some manifestations clinically.

Which is why, if you use today's "DSM" categories, let's say ADHD for example, or major depression, you're unlikely to find one single biomarker. Because what is today ADHD and major depression includes more than one disorder; it encompasses multiple entities.

(11:23) Complex conditions like ADHD and depression may have multiple biological factors rather than a single marker.

Rae: This made sense to me. You'd never expect to find a biomarker for a headache, because a headache could be from dehydration or a lack of sleep or — hello, late-night Google habits — a brain tumor. Headaches could be caused by so many different things, there's just no way we'd expect a single biomarker to be able to say, "This is a headache."

And Anand is saying it's kind of the same thing with ADHD. The more factors there are contributing to the cause, the harder it will be to find a single biomarker that tests for it. But again, as Anand tells it, that doesn't mean biology can't be useful.

Anand: If there are 10 causes — I'm just being facetious — there are 10 causes of ADHD, let's say seven of them are biological and three of them are psychological, you'll never find a biomarker that explains all this. But if you find a biomarker that is implicated in a significant subgroup, let's say 20%, 25%, 30% of a category of patients have a consistent biomarker, I think it enlightens.

Rae: I really appreciate that, because I think so rarely do we get to speak about things in all their complexity. And ADHD, as someone who has it, is a very complex thing.

Anand: Yes.

Rae: So, of course it makes sense that we wouldn't necessarily find one specific test or marker that would encapsulate the entire experience, which can be extremely varied, as you say, among the subtypes. It's nice to know that that complexity is not a barrier to ever finding anything that could help us make progress and have more targeted treatments.

Anand: The purpose of science is to deal with complexity.

Rae: Yeah.

Anand: It's not to walk away and find the easiest questions. A good scientist always tries to take the big challenges and see what I can do with it.

Rae: As you explain that, something that keeps kind of coming to me is how complex this really is. I think, you know, when you are experiencing one of these many things, there is a desire to boil it down to something that feels objective: "This is real, my suffering is real."

And I want to take maybe a little detour into the gap that lack of certainty can create and the things that maybe crawl in to fill it. Because I know there are a lot of things out there touting biomarkers: a brain scan, a blood test that can tell you if you have depression, can tell you if you have ADHD. And a lot of people find that very appealing because it does offer this certainty that may be lacking, and I can see why they would want it. Are those legitimate in any way?

Anand: Most of them are not. My advice to folks is, anyone who charges a lot of money and says, "I can show you brain scans," you know, there's the razzle-dazzle, the sizzle that sells the steak. Please be very skeptical. Ask for the evidence base. Look it up. Because I think in the absence of hard-core, definitive findings, charlatans prevail.

This is what the "DSM" group is also very concerned about. They are concerned about endorsing something that someone will say, "Look, I've been telling you this for years." But they want to be very careful. There's appropriate caution, there's abundance of caution, and the "DSM" needs to walk a thin line.

Rae: So, with this slow progress and with the new "DSM" coming our way, not immediately, but quite soon, what would we actually be adding?

Anand: Let's go to depression, let's go to schizophrenia. There are no laboratory tests for these disorders. So what the "DSM" group did when I was part of it, recognizing that outside the dementia realm there are no clear-cut biomarkers, we introduced the concept of biological factors.

These are processes, such as immunological mechanisms, that are associated with a disease, most notably depression, but have not crystallized into a lab-testable biomarker.

(15:31) The discussion shifts to how biological factors could practically improve treatment for mental health conditions.

Rae: Okay, this might sound like annoying semantics, but it's actually an important difference. Basically, Anand is saying that we may not have a blood test or a brain scan, a biomarker, that can perfectly identify most mental health conditions. But there are other measures that he's calling biological factors that could, in theory anyway, still be useful for diagnosis and treatment.

For example, about 30% of patients diagnosed with major depression have higher levels of certain immune molecules in their blood. A common one is called CRP. Now, that doesn't mean a doctor can draw your blood to find out if you're depressed. But there's some early evidence that it could help predict which antidepressants might work for you.

Anand isn't saying we'd add CRP to the "DSM" right away, but this is the kind of biology he thinks is promising.

Anand: It's early, so the "DSM" is reluctant to make a definitive statement. But in a subgroup of patients, they might have clinical implications that may be meaningful at a practical level. That's one example.

Rae: That makes sense to me. The idea that there is a trackable thing that you can add to this, something that you could improve, or test, or see if it's interacting differently with something else, feels almost calmingly objective for the treatment of mental health, as opposed to just saying sometimes, I think, "Do you feel better?"

Anand: Yes.

Rae: "Is this working? Do you think it's working?" You could say, "We know it's working, and here's how we know."

Anand: Right. You know, I think there are others who would say we are not there yet, and they would be correct to a large degree, but not entirely. You don't get there — waiting for the perfect day, for the epiphany, for the one definitive paper that changes everything may or may not happen. Science can be a game of inches. You incorporate them as and when they come.

And the next "DSM" is attempting to do that. They talk about a living document that as findings come about, when they're reliable findings, we'll incorporate them. Incorporate them in a way that's scientifically solid and meaningful without prematurely selling something as a blood test for condition X.

Rae: When you explain it that way, it sounds like it has the potential to completely change what has in the past occasionally felt like — and maybe because this is what was available — kind of a scattershot approach. We'll try this pill, or we'll try this therapy, or we'll see if this works.

It would be, and I have to say as someone who's experienced this, wonderful to walk in to my doctor's office and be prescribed something that is highly likely to work for me or given therapy that is highly likely to work for me because there's some objective basis.

Anand: Sure.

Rae: I mean, it really does sound wonderful. I have to then ask, when things start to sound so wonderful, what the risks might be. Are there strong arguments, like you said, in the other direction? Some people are not fully on board against adding biology to the "DSM", and what are those?

Anand: The only risk, in my view, is if you add something or recommend something that has no valid scientific basis for fear of offending someone or fear of offending a constituency. That would be a mistake. But if the science is there, you should go ahead and make a recommendation.

(18:54) Rae and Anand explore the ethical and insurance risks of relying on biological markers.

Rae: Can I pitch maybe a question...

Anand: Sure, of course.

Rae: ...about this? Say there was a biomarker like this that seemed very, very promising, and we all know that the "DSM" is used as a way to get insurance, to get coverage, to get treatment, right?

Anand: Correct.

Rae: Say I was an outlier in one of those groups. I have depression, but the type I have does not match the biomarker for the subgroup, and people are using it. And I take that test, and then it turns out that my symptoms don't seem to fit in, or I don't meet the criteria on the biomarker.

Could it end up that someone's test doesn't work, and then that person is not able to get covered or get accommodations in school, and it's really just simply something where science is still unfolding and we haven't found a way to test for the type that they have or the thing that's going on with them?

Anand: Sure. It's not easy to get, let's say, a blood test or a brain scan approved by the FDA. It is a long, lengthy process. Some say too lengthy, some say not lengthy enough, but they are very careful about looking at the evidence before they approve something. And without FDA approval as a biomarker, you're unlikely to get reimbursed by insurance companies.

So the Alzheimer's test was approved, and now many insurance companies reimburse for that. There's a danger there too. It can get over-interpreted, overused, given to patients who have no cognitive challenges. There's always the risk. Having a biomarker doesn't solve all problems, needless to say.

Rae: Are you saying I'm not the first person to think of this?

Anand: Well, you may be the second.

Rae: I'll take it.

Anand: The whole thing when it comes to brain science is incredibly complicated, and you bring up important questions about what's the ethics of all this. Similarly, tomorrow — it's unlikely, let's say there's a test for CRP. We're not there yet, and I don't want the viewers to think I am pushing CRP as a test, but it's a promising area.

And someone comes to me and says, "I'm depressed," I diagnose clinical depression, and I say, "Listen, there's a particular blood test I could do. It may help me think about treatments that are more precise and tailored to you." And the patient might say no. Informed consent is the key. They might say, "I don't want that test." Or they might say, "Why not give it a shot? Even if it's not 100% accurate, if it gives some degree of precision, some degree of scientific objectivity that can add to clinical judgment."

Right now there's nothing. Right now there's just clinical impressions. Doctor X says, "I have experience with this treatment, and I will try that." I think it's a step forward. Biological markers to predict treatment response in psychiatry is about 50 years old, that field. It's been filled with early promises and later disappointments.

My encouragement and support of "DSM" introducing biology is the science is in a better place today than it was 10, 20, 30, 40 years ago. And let's start introducing biology into the "DSM" conversation.

Rae: Anand, thank you so much. This has been genuinely and deeply fascinating.

Anand: Well, thank you very much. You're obviously very knowledgeable. Your questions are very direct, very probing.

Rae: Many thanks to Anand Kumar for speaking with me. If you want to hear more about adding biology to the "DSM," check out his piece in "The Conversation." We'll link to it in the show notes.

If you liked this conversation, you might like last week's episode with Awais Aftab about whether ADHD is a spectrum. Thanks for listening. See you in two weeks.

"Hyperfocus" is hosted by me, Rae Jacobson. Our producer is Cody Nelson, and Anna Rothschild is our senior podcast producer. Julie Subrin helps with booking.

Our music comes from Blue Dot Sessions. Our research correspondent is Dr. K.J. Wynne. Our associate director of content development is Calvin Knie. Briana Berry is our production director, and Neil Drumming is our editorial director.

If you have any questions for us or ideas for future episodes, write me an email or send a voice memo to hyperfocus@understood.org.

This show is brought to you by Understood.org. Our executive directors are Laura Key, Scott Cocchiere, and Jordan Davidson. Understood is a nonprofit organization dedicated to empowering people with learning and thinking differences like ADHD and dyslexia. If you want to help us continue this work, donate at understood.org/give.

If you have any questions for us or ideas for future episodes, write me an email or send a voice memo to hyperfocus@understood.org.