Is ADHD genetic? We asked a Harvard scientist

We’re back with another episode from our Hyperfocus field trip to San Diego. While we were at the APSARD (American Professional Society of ADHD and Related Disorders) conference, one of the talks that really piqued our interest was on genetics and neurodevelopmental disorders, including ADHD. 

Genetic science is tough to understand. And, as you’ll hear in this interview, we had a lot to learn and a lot of questions. Is ADHD genetic? And if it is, what does that mean for people who have it? What does it mean for treatment? 

Luckily, Dr. Anne Arnett, a scientist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical school, was kind enough to brave a chilly, windy outdoor recording. In this conversation, she help us understand more about what we know (and what we don’t) about ADHD and genetics. 

We love hearing from our listeners. Email us at hyperfocus@understood.org.

• Video: Dyscalculia, dyslexia, and genetics 

• Can genetic testing help me find the right ADHD medication?

• Is ADHD hereditary? 

• ADHD runs in the family (Michelle’s story)

• The Arnett Lab at Boston Children’s Hospital

(2:01) Is ADHD genetic?

(8:28) Genetic vs. environmental factors and ADHD co-morbidities

(11:50) What does the latest research mean for people with ADHD?

(13:55) Is there genetic testing for ADHD?

(18:56) Why bother with early detection? 

(21:44) Anne’s goals for her research

Rae: Every so often, you hear something that's simultaneously incredibly interesting and absolutely over your head. It's exciting and a little annoying. I hate it when you can tell something is fascinating, but because it's a dense subject or just a really new topic or something that has a lot of jargon, you can't really understand it. It makes you want to pin down the person who does get it, and make them keep explaining it to you until things finally make sense.

Usually this is not possible, but dear listeners, we have a podcast, and making people explain things that are cool but confusing until they start to make sense is from what I can tell, basically the entire point of podcasts. So, as I sat in a big, packed hotel conference room listening to Dr. Anne Arnett talk about her work on genetics and ADHD, I felt a surge of joy.

Anne is a scientist at Boston Children's Hospital and an assistant professor of pediatrics at Harvard Medical School, she and her colleagues had come to APSARD, which stands for bear with me. American Professional Society of ADHD and Related Sisorders to present their work on genetics and neurodevelopmental disorders. It's very much a work in progress, but the goal is to eventually figure out what, if any, role genes play in disorders like ADHD and autism spectrum disorder. Then, they want to use that knowledge to help scientists build better treatments and understand more about the disorders themselves.

The talk was fascinating, and I understood about half of it. OK, maybe more like a third. But when she was done, I got to do what I always dream of doing and have Anne sit down next to me and explain it until it made sense.

Before we jump in, I should say that we had to record outside again, and it was very, very windy. So, please bear with us through sniffles and wind sounds and any birds you might hear. This week on "Hyperfocus," Dr. Anne Arnett.

So, I guess my first question is, is ADHD genetic?

Anne: Yeah, that's an interesting question. So, ADHD is definitely inherited through family. So, we call it heritable, meaning that it gets passed down through families and that within families or even within the population, most of the individual differences and ADHD traits and symptoms is due to genetic factors. But there's a difference between something that's heritable and something that's genetic. When we say the word genetic, we're talking about known genetic causes, like a single gene or a set of genes that are causing ADHD.

And right now we can't explain all the differences in ADHD with those known genetic differences. So, we look at like common variability in the genome or in the DNA. Those are small little changes that everybody in the population has. It's what makes us who we are. And then we also look at rare variants. Those are changes in the DNA that really affect the way the DNA creates a protein.

Rae: So, just, I'm trying to make sure I'm understanding you correctly. A common variability is something that everybody has a little bit, like everyone's genetic profile is going to be a little bit varied. And in rare variants are things that stand out?

Anne: Yeah. So, for each gene, there are a few different versions of the gene that are really common in the population. So, that's what we would call a common variant. And then there are versions of the gene that can happen either spontaneously at birth or can be passed down through families that are really rare. Like they might be like 400 in the entire world. 400 people in a world have this kind of change to a particular gene, for example.

So, for a long time, we really thought it was only those common variants that were sort of adding up an increasing vulnerability for ADHD. But now some of the work that we're doing in Boston Children's with my colleague Ryan Doan, is revealing that there are quite a few of those more rare changes to the DNA that are also contributing to ADHD in some families.

Rae: So, do you say it's passed down through families, does that mean, like, for example, my husband has a widow's peak, and my daughter has a widow's peak. Like that's a genetic pass down that I could understand.

Anne: Yeah.

Rae: But it sounds like it's more than that because it's the heritability piece which is the inherited piece comes in?

Anne: Well it's similar. It's similar to physical features. Some physical features though are explained by just a few of those common variants. You know, we kind of know that there are only maybe a handful of those common variants that contribute to the widow's peak. But in ADHD, it's lots, I mean, like hundreds of genes are involved in and brain development that leads to someone's ability to regulate their attention and their activity level and their emotions and all those things. And so, it's just a lot more complicated.

Rae: So, can I ask what might be a really basic question, but does that mean that you can like if you could look at a map of my genes I have ADHD. Would you say like, "Oh, this one and this one and this one that adds up to having ADHD"?

Anne: Only if there was one of those rare variant changes, and if it was a rare variant change that we've seen in other people who have ADHD or autism, or if it was a rare variant change that we also see in your family members who have ADHD.

Rae: So, my mom has ADHD. And I know when you talk about it runs in families. Is it just that it's genes passed down, or are there other factors that make that happen?

Anne: So, yeah, that's a great question. Genes get passed down. The environment gets passed down. So, genes are, the role of gene, of the gene is to essentially create a protein and the creation or expression of that protein in your body can be either increased or decreased depending on something that's going on in your environment.

Rae: Help me understand that a little bit more.

Anne: So, for example, there are genes in our body that are like cancer suppression genes or tumor suppression genes. And when you smoke cigarettes, for example, there's something in those chemicals that could deactivate or sort of silenced that tumor suppression gene so that the tumor can be…

Rae: That's how smoking causes cancer?

Anne: In a very simple way, yes.

Rae: I never knew that.

Anne: Yeah. That's one example of how cancer can proliferate. Yeah.

Rae: So, if I'm understanding it, you introduce things from your environment and you have whatever your genetic profile is at birth and then your environment and the things around you, whether it's growing up in a household with cigarette smoke or can it even be something like having a parent who's very disorganized?

Anne: Yeah. Well, typically we think of like a chaotic environment as something that could exacerbate ADHD symptoms in a person who's already vulnerable for ADHD, probably genetically vulnerable, but probably not causing ADHD. The environmental things that can cause ADHD are going to be like really extreme environmental adversity, like neglect, like kids in Romania, for example, who were institutionalized 20 years ago and had really poor care in the first two years of their lives. And, you know, very little social interaction.

Those kids have really high rates of ADHD. And we think it's because they had this really extreme environmental deprivation early in their lives that's not quite home chaos, right?

Rae: Yeah.

Anne: Like that's at a different level. Other environmental things that could cause ADHD or, you know, if your mom was drinking when she was pregnant with you, you know, prenatal alcohol exposure can cause ADHD. So, most of the environmental contributions that we think about, like red dyes and chaotic homes, have actually really small contributions. But there are a few more extreme environments that can explain a lot of it.

Rae: So, the fact that my mother could never find her shoes is probably not why I have ADHD.

Anne: Right, but if she wasn't able to as a result, like model good organizational behaviors for you, it probably didn't help.

Rae: Right. So, the genetic role in ADHD is it sounds a little bit like a lot of people have the potential to develop ADHD, but not everybody does. And environment influences that or no?

Anne: The genetic contributions are really strong. It's like 75% of the variability is due to genetic factors on their own.

Rae: OK.

Anne: And so, then the individual environment causes are only 25% of that. So, I wouldn't say that there are a whole lot of people with vulnerable ADHD genes who don't go on to develop ADHD.

Rae: OK.

Anne: But the severity of their symptoms and the degree to which it's causing functional impairment, that's probably moderated by the environment a lot.

Rae: So, you're going to have it. But the environment that you grow up in is either protective or exacerbating.

Anne: Right.

Rae: Got it. So, understanding on the basics, which I feel like I kind of now have a grasp on, you also talked a lot about co-morbidity with ADHD, other genetic things that come to light, like bipolar disorder or major depressive disorder or schizophrenia, that there's a lot of overlap. Could you help me understand that a little bit more?

Anne: Yeah. So, let's start with this common variance. When we look at the common variants that we think contribute to ADHD or are related to ADHD, a lot of them overlap with the common variants that contribute to things like anxiety, depression, and schizophrenia. So, just essentially, the genetic basis for the two disorders is very similar.

Rae: So, I wonder about that a lot because we hear, you know, I write about this, I have it, I try to learn as much as I can. And you often hear that people with ADHD are at much higher risk is the words that they always use. Much higher risk for major depressive disorder, for anxiety especially, for a lot of other disorders, is comorbidities.

And I think a lot of what I understood about it, kind of up until now was that, you know, people would be like, "Well, yeah, of course you're anxious if you can't get things done on time, if you're always late, if you're having these, like, true executive functioning issues that come along with ADHD, it's going to cause a lot of anxiety and it may cause depression as well." But it sounds like, in a lot of ways, the co-morbidity is much, much deeper than that.

Anne: It could be. So, we're actually looking at this right now in some of our data. I think there are two pathways to the co-morbidity. So, let's take anxiety for example. Like you said, one pathway is that ADHD causes difficulty staying organized and being successful at your job and maintaining friendships. That's going to make you kind of anxious or sad or low, you know, got stressed out, right? So, that's sort of what we would call a good mediation path. It's through the functional challenges. Another pathway could be that the cause of ADHD is also causing the anxiety.

Rae: Yeah, that's the question I think I have.

Anne: So, it seems like both of those pathways are true. And they may be...

Rae: Confused yet? OK. Let's sum things up a little bit. ADHD is heritable, meaning it can be passed down through families. But that does not mean it's guaranteed that if one or both parents have ADHD, their child will also have it. The environment plays a role, as does the way the person's genes are expressed.

Another interesting thing Anne told me was that the genetic basis of ADHD has a lot in common with mood disorders like depression and anxiety, which could help explain why those disorders so often go along with ADHD.

That's all to say, it's complicated. And it got me wondering, what does this all mean? Especially for those of us who have ADHD. Anne herself acknowledged that it's pretty hard to explain.

Anne: Let's say we could look at someone's genome and say, OK, you have a change in your DNA that's been associated with ADHD before. And actually a lot of those people who have this sort of change and ADHD also have anxiety. If we know that early in life, before you start experiencing a lot of difficulties with ADHD and the anxiety, the hope is that we can give you some of the tools and the resources you need so that you're not experiencing that as like a deal breaker, you know that.

Rae: Yeah.

Anne: But it's not really getting in your way that it's not to super severe for you. So, that's one thing. And the flip side could be we might have to, like different treatment approaches for somebody whose anxiety is secondary to their ADHD problems, right? And then we could just really focus on decreasing the impairment caused by ADHD.

Rae: Would it help you know what to treat first or how strongly?

Anne: Yes. So, we often see kids who have, they present with ADHD and anxiety, and the parents are like, you know, "What should we do first?" And it's not an easy question. So, if we knew that the ADHD problems were causing the anxiety, that would be an easy answer, right? Let's treat the ADHD. If we knew that it was both, we might say, "Well, let's try, you know, maybe a medication for ADHD and see if it also decreases the anxiety. But let's try to target both at the same time."

Rae: So, this could become kind of a roadmap for treatment for how to do it, what order, what's best, what to target. There's like long-term implications.

This is a question with two pieces, both of which, well one of which sounds kind of like sci fi to me a little bit, I have to say. It is like if you had the ability to do some type of genetic testing, like when I was pregnant, I got a genetic testing panel, which I think most people do to see if my daughter was going to have any potential conditions that we could deal with later. Down syndrome?

Anne: Yes. Of course.

Rae: Is there some universe in which something like that is done for ADHD, especially if there's a early you know? I know that I had it, there's a good chance she's going to have it. We test, and it makes early intervention much more realistic for more kids. Like, is that something that is like a desirable thing, or does that also feel maybe like it has the implication of being like, well, we think this is going to be your life, so we're sort of getting ahead of ourselves.

Anne: Yeah, that's a great question. I get this question a lot. I think it's going to be really individualized to the patient. You know, if that sort of testing is available, just like in pregnancy, people should have the option to do the test and to know ahead of time what a result would mean for them and whether there is anything we can do about it. You know what it would mean they could expect.

And, you know, I think in the best case scenario, it's like you said, if a parent knew when their child was really young that they had this genetic sort of vulnerability for ADHD, we could potentially give the parent some skills that would make parenting that child easier and make the child's life easier, sort of get ahead of...

Rae: Yeah.

Anne: Some of the challenges that kid could face in school and with friends, etc..

Rae: So, you build the scaffolding earlier in life as opposed to waiting to see what happens.

Anne: Exactly, exactly.

Rae: I guess the flip side of that, which I could imagine someone arguing, is that then you're writing a kid's story before they're even started.

Anne: Not really. I mean, so the types of interventions I'm talking about are behavioral interventions, and it's like super parenting. Like, honestly…

Rae: Superparenting. I love this idea. Tell me more.

Anne: Great skills that every parent could use.

Rae: Yeah.

Anne: I think any of it is harmful. None of it is like, "Oh, do this with a kid with ADHD, but not with your typically developing kid." I would never, you know, all these skills are really useful. So, I don't think there would be any harm in trying to get ahead of it and then acknowledging that, you know, you have an infant right now. We're not diagnosing them or ADHD. We're saying these are some things that you could potentially...

Rae: You could potentially do.

Anne: Protect gainst, right? Or just try to bolster. You know, I think, I mean, I work with kids mostly, right? So, and in kids with ADHD, I like to think of this like the most extreme version of kids, you know. Like they're the most impulsive, or the most loud, or the most gregarious, and they're also the most loving and affectionate and, like, determined sometimes and really into stuff. And they, they're just like they are childhood embodied.

Rae: Yeah.

Anne: And so, there's so much wonderful, there's so many wonderful things that can come out of that, including all the things that we talked about: creativity, you know, thinking outside the box, just having a lot of energy and enthusiasm for life and work, etc.. And so, it's not that we want to decrease that, I just want to get the other part out of their way so that we can bolster those strong.

Rae: We can help clear away the executive functioning things and build it. Everyone always talks about building skills and strategies and the scaffolding and all these things you can do for people with ADHD.

Anne: Or even like, you know, tell the teacher that this is what's going on when the child enters preschool so they don't get kicked out of preschool because they're being expected to perform like every other child in the classroom.

Rae: Yeah, maybe it's a way to get ahead of some things.

Anne: Yeah.

Rae: As opposed to waiting for them to become a problem.

Anne: Right.

Rae: But I also hear in that, that you're saying, and this is something that we hear a lot for ADHD stuff, that it's a universal design piece, where it's like, it's not like you're going to edit out a kid's personality by doing these things. You're not recommending putting them on stimulants when they're two. What you're saying is you can make life easier. And even if they don't necessarily develop ADHD, these are going to be skills that benefit them no matter what.

Anne: Exactly. That's the hope.

Rae: So, yeah. That makes a lot of sense to me. And it seems like almost something we should be doing regardless of whatever comes out of this type of research.

Anne: And then, you know, the other part of this is that some of the rare variants that we study that we have associated with ADHD in families, different kinds of changes to those same genes have been associated with autism and intellectual disability, and some medical side effects like seizures or changes to the brain development, or maybe cardiac problems. Like there are some other features that can come along with a gene change that would be really helpful to know from a medical standpoint.

So, I'm a, I personally, I think because I'm in science, like I like to know more.

Rae: Yeah.

Anne: And some parents also just want to know what's the reason for this, and that's enough for them. But I also really respect the parents who are like, this is my kid, regardless of what it says on that piece of paper or so, it's just not an interest.

Rae: It's the kind of thing that feels so new. It feels so modern, and it feels like you could find a lot of controversy within it. And you could also find a lot of ways that people would be really happy to receive it. Like it's an interesting new perspective, especially when you think of neurodiversity as something that's like a burgeoning identity for a lot of people.

Anne: But that's been going on with prenatal testing forever.

Rae: Something I think about a lot, and something that a lot of people with ADHD often ask each other, is, "If you could get rid of your ADHD, would you do it?" For me, the answer changes by the hour. Was it a good week, a bad week? Am I feeling creative? Am I feeling disorganized? It really depends. And all this talk about genes made me wonder if we can identify the genetic markers for ADHD. Is there a universe sometime far in the future where we could simply choose not to have it? Or, and this felt a little bit more realistic. Could a person's genetic profile one day help with early detection and, through that, early interventions for ADHD? I ran all this by Anne to see how she's thinking about it.

Anne: I can't speak for people with ADHD about whether they would want to get rid of it or not. That would never be my choice. It's not my goal currently. You know, my goal would be earlier identification to provide families with the scaffolding, like you said, to just support these kids. I think the idea that the genetic data could tell us about co-morbidity is also really important, because some of the most impairing features of ADHD aren't the inattention and the hyperactivity, but the things that come along with it, like the anxiety, like substance abuse, you know, that's a huge problem.

Juvenile delinquency, kids ending up in in juvie because they've made impulsive choices and gotten in trouble with the law. Like some of those things are pretty big, right? And it would be nice to know specifically what we need to have a heads up about and how we need to support each person individually with ADHD.

I think the other thing is, as I said, a lot of these genes that we're discovering have already been associated with autism and intellectual disability. So what we're doing is broadening what we call the phenotype, the behavioral sort of manifestations of the gene, so that if there's something like severe intellectual disability or profound intellectual disability, where maybe you would think about using CRISPR to change the genome.

It's important to know that there that different changes to that same gene could result in profound intellectual disability or mild ADHD or anxiety. You know, it's important to know that it's ,that there's nuances to this.

Rae: Maybe I'm misunderstanding, but it sounds like you're saying genes aren't, it's like somebody wrote your future in your genes. So many things can happen. A genetic profile isn't necessarily a personality or a person at all. It's simply things you can know and learn from, hopefully. But not every single thing that's in your genome is going to be expressed. Is that right?

Anne: Right. That's definitely true.

Rae: In you're like, dream of dreams, I can have anything I want, the store is free, what do you hope this will achieve? Your research, the things that you guys are doing now ten, 15 years down the line, 30 years, what do you see happening?

Anne: I do think there's a lot of value in people understanding themselves. You know, as I said, there isn't much we can do with this information on an individual basis right now. But when we do let families know that we've found a variant, there's a sense of relief often that they just kind of understand themselves and their family or their child.

And then, you know, the other thing that comes along with that is that they're suddenly part of another community, a new community of families who have a change to this particular gene, for example, these family groups for different genes. So, yeah, I think helping people understand themselves to the degree that they find helpful is sort of the ultimate goal.

Rae: I love that. I love that as a science goal, too, because it's, you know, it's something in the ADHD community, we talk a lot about the value of belonging, of understanding who we are via what we know about our brains. And you can celebrate it, or you can try to work with it, or you can do all sorts of things with it. But knowing who you are and that you're part of a group of other people who understand is everything.

Anne: Yeah, absolutely. I mean, we talked today a little bit about the evolution of the ADHD profile and how some of these traits were really adaptive.

Rae: Yes.

Anne: Many, many, many years ago. And now we've created this society where these traits don't always fit in well. So, when you find a community and you feel like you've found a place for your traits where they are valued or respected, and I think that's so important. And everybody has that to some degree, right?

Rae: Well, you hope, I guess. I love that. Thank you so much.

Anne: Yeah, sure.

Rae: This was awesome.

Anne: Yeah.

Rae: Hyperfocus is made by me, Rae Jacobson, and Cody Nelson. Our music comes from Blue Dot Sessions, and Justin D. Wright mixes the show. Samiah Adams is our supervising producer. 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 Seth Melnick. 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.