What are common comorbidities with ASD and how difficult is it to differentiate these conditions from overlapping symptoms of ASD? What guidelines are there for managing agitation in autism spectrum disorder?

Robyn Thom, MD, is a child, adolescent, and adult psychiatrist at the Massachusetts General Hospital (MGH) Lurie Center for Autism and co-Director of the MGH Williams Syndrome Program. She is also an Assistant Professor of Psychiatry at Harvard Medical School. She specializes in diagnosing and treating comorbid psychiatric conditions in individuals with autism spectrum disorder and other developmental disabilities including Williams syndrome. Dr. Thom's research interests include psychopharmacology, anxiety disorders, Williams syndrome, medical comorbidity in adults with autism spectrum disorder, and brain aging.

Sabrina Siegel with the Neuroscience Education Institute.

On this show, I sit down with renowned mental health care experts from a range of diverse backgrounds to discuss breakthroughs and best practices for treating patients with mental health conditions.

In this episode of the NEI podcast, we are discussing autism spectrum disorder and comorbidities.

She treats both children and adults across the lifespan with autism spectrum disorder and comorbidities.

She is a psychiatrist at the Lurie Center for Autism at Mass General Hospital and assistant professor at Harvard Medical School.

My first question for you is how did you get interested in treating patients with autism spectrum disorder or ASD?

Well, back when I was a first-year medical student, long before I knew I would even become a psychiatrist, I was a volunteer swim instructor for kids with disabilities and several of them had ASD.

It was a really neat experience trying to find nonverbal ways to communicate with these kids and to try and understand where people are coming from when their brains are wired in such a different way.

They have such different experiences of the world.

So I think that was the first inkling that this might be for me.

I put that to side when I went through the rest of my medical training and then actually went into psychiatry not fully knowing I would do ASD, but things really solidified for me towards the end of my training, particularly with excellent mentorship, including from the director of the Lurie Center, Dr.

And as I got exposed to more and more patients, I really realized that there's this huge need and opportunity, both on the clinical and research sides, and that just makes it an endlessly exciting space to work in.

How is autism spectrum disorder actually diagnosed?

So ASD is a behaviorally defined diagnosis just like any other mental health condition like ADHD or anxiety or depression.

And What I mean by that is there's no specific lab test, brain scan, or even like a neuropsychiatric measure that can definitively say that yes, a person has autism or no, they definitely don't.

So, you know, it really comes down to like a clinical evaluation, trying to really understand if the person has the definitional criteria for ASD and if they do, really trying to make sure that they're due to ASD rather than some other cause like normal childhood development or another psychiatric disorder.

You know there's times when we can use tools to help gather the information things like standardized rating scales or questionnaires or structured interviews or observations.

Tools like the ADOS or the ADIR, these are like really the gold standard tools that we use for research, but you know practically speaking are often like really time-consuming, impractical, create barriers to care, and are often not necessary in clinical practice.

With that being said, what are the major symptoms of ASD and how is this different across the spectrum?

That's a great question and I'm so glad you asked it because ASD and the definition of it has changed a lot, like even recently.

I'll give you the most recent definition that came out in

and in that definition there are 2 core symptom buckets.

So the first bucket is the social communication and interaction difficulties.

And the second bucket is the restricted repetitive patterns of behavior.

Everybody with ASD has to have both, but the severity can vary widely.

So, I consider social communication challenges really the heart and soul of ASD.

And on 1 end of the spectrum, you can see people who are very interested in having friendships, really want them, feel lonely when they're not around people, but really struggle doing that.

So I have kids as young as like 9 or 10, and they come into my office and I say, what does it mean to have ASD?

And they say something like, it means that I'm being annoying even if I don't mean to be and sometimes that means people get mad at me or don't want to play with me.

Oh yeah, so that's actually really good insight and that we see that, you know, on the less severe end of the spectrum.

On the more severe side of the spectrum, we definitely also see folks who may have like no verbal language at all, really don't desire social relationships, may get very anxious or frustrated when they're around people, be kind of ambivalent even when like family members are around them, and really be much more interested in like what's going on in their heads than responding to other people or the environment.

That's, wow, yeah, that is so interesting.

What are some of the greatest challenges when it comes to treating ASD?

Well, you know, 1 thing that I think is really important to mention is that we're not necessarily looking to treat ASD per se.

A lot of people who are affected by ASD find this idea kind of offensive or undesirable, and that's really understandable.

You know, I think a better way of looking at it is like how do we support people with ASD to live their fullest lives so that they're happy, healthy and accomplishing their goals.

Of course in doing that there are several challenges.

You know, 1 thing that comes to mind is that although ASD actually affects, it's not rare, it affects about 2% of the population.

I would say like medically, it's still considered a specialized area, meaning that most people get ASD care in specialty clinics.

Of course, these clinics are usually limited to like urban areas where there's a big medical center and have these huge long wait lists.

So that's a huge challenge, just accessing care.

And there's definitely racial and socioeconomic disparities.

I would say that another challenge is research and treatment development.

I would say that in the last 10 to 20 years, we've really come a very long way on the behavioral and non-medication therapy side.

But really, I've got to be honest with you, progress on the drug development side has really lagged behind

the point that you know there are no drugs or medications that treat those 2 core symptom buckets that we talked about, the social impairment and the repetitive behaviors.

And actually the Food and drug administration, the FDA has only approved 2 medications for all of ASD.

That's for irritability, which means really bad tantrums, aggression, self-injury, that serious stuff.

So that's a huge challenge on the treatment side.

Are there certain challenges that, I mean related to that, are there certain challenges in conducting clinical trials for medications for in autism?

Yeah, I'm so glad you asked that question.

I think doing clinical research is challenging and tough no matter what field you're in.

But I do think that doing it in ASD brings some specific challenges.

First and foremost, you know, like we talked about earlier, ASD is really behaviorally defined, meaning does the person have, you know, a certain number from this list of symptoms?

We really don't know a whole lot about why some people are on that really severe end of the spectrum that we talked about versus like the kid who's like 9 years old and could say, yeah, sometimes I make social mistakes.

We don't know what's going on in the brain.

And although we call those 2 presentations the same thing, ASD in reality, they're probably not.

If we're enrolling people with, like, across the whole spectrum and these trials, they have a whole different variety of combination of ASD symptoms.

It kind of makes sense that a lot of trials come to inconclusive or negative results.

The other thing that's really tough is that in like mental health and general psychiatry, there are a lot of measurement tools that Lots of people have devoted a lot of time and attention and energy to developing to measure things like how bad is the anxiety?

Does it get better after a medication or a specific type of therapy?

We really lack those types of measures in autism.

And that's important because if you're using the standard general population measures for anxiety, things like how often do you worry, what are you afraid of, if you're trying to use those measures in someone who has really limited language, you're not going to get very far.

What kinds of treatments are there for ASD symptoms and how would you say it's treated?

Yeah, so the most evidence-based treatment for ASD is behavioral therapy, something called applied behavioral analysis.

You may have heard of it referred to as ABA.

There's a lot of strong scientific research showing that it can really help to support social skill development.

And an ABA framework or principles can also be really helpful for increasing positive behaviors and learning important skills, you know, everything ranging from life skills like how to make a bed, how to do your laundry, how to prepare a meal, to academic skills, and it can be really helpful for decreasing unwanted or less desirable behaviors.

So, you know, along these lines, I'm thinking things like self-injury or aggression and things like that.

Yeah, but you know, no 2 people with autism are alike, so ABA may not be for everyone and above and beyond ABA, it's also really important to look at the individual and what areas they may need some extra support and treatment in.

So, you know, many of my patients do things like speech therapy.

Speech therapy can really help people develop more verbal language.

But even for people who have no verbal language at all, Speech therapy can really help by developing communication devices and tools like picture flip books or now we have these really cool technologically advanced programs that people can use on iPads and things.

And then, you know, even for people who have less severe ASD who have like fluent speech, full sentences, all of that, speech therapy can really help with what we call the pragmatics of speech.

So, like what's kind of underneath that like level of words.

Yeah, like more of the social nuances of speech.

Is there anything else that, you know, it could help?

You know, 1 thing that we haven't talked about specifically yet is 1 of the symptoms inside that repetitive behaviors bucket.

It doesn't quite fit, but it's sensory abnormality.

So, that's actually a symptom of ASD and it can go in both directions.

So some people with ASD are hypersensitive, so they experience things like noises, lights, sounds, touch more intensely than someone without ASD.

And other people are actually hyposensory, meaning that they sense input in a less intense way.

So sometimes these kids or adults are really seeking sensory input by like putting certain foods in their mouths that have a strong sensory input like sour things for example.

I have a patient that like loves pickles or you know kids who are like crashing into walls because they need that like sensory input in their bodies.

Occupational therapists can be really helpful for creating something called a sensory diet so that the person's sensory input is more regulated.

And occupational therapists are also really helpful in breaking down teaching and practicing life skills.

That really kind of comes into play in like adolescence and early adulthood.

We've talked about this a little bit but I'll say it again, we really don't have medications for those core symptoms of autism And it's important to know where our limitations of medications end, right?

So that you're not trying to prescribe or try a medicine if it's really not gonna help.

I will say that medications can be really helpful for when there's a mental health condition on top of ASD.

So by that, a sleep disorder, attention deficit hyperactivity disorder or ADHD, anxiety, a mood disorder, this is where psychiatric medications can be very helpful, sometimes alongside psychotherapy as well.

What guidelines are there for managing agitation in ASD?

Yeah, that's a really, really important topic.

Unfortunately, agitation can be quite common in people with ASD.

I would say, you know, maybe up to half of people will struggle with this at some point.

There's actually a really helpful framework for thinking through agitation.

I kind of try and break it down into 4 steps.

So the first thing to do, first and foremost, it's really important to be 100% sure that the agitation is not due to an underlying medical issue.

Things as like common and simple as constipation, an ear infection, a dental cavity can cause like serious agitation.

And obviously, until you treat that medical issue, like fill the cavity, make sure the person's bowels are moving appropriately, the agitation will not stop.

And it would be like honestly, a terrible shame and injustice to the patient to not be treating their medical condition.

So that's first and foremost to really be doing like a head-to-toe systematic look to make sure that everything is functioning as it should be.

And sometimes you need we need the help of specialists like family doctors or GI doctors or ear, nose and throat specialists or dentists to really make sure we're doing a good look.

The second thing I do is I come back and I say, okay, the heart and soul of autism is this challenge with communication.

So, really trying to think like, is this agitation a communication of something?

And doing everything we can to support communication so the person can tell us whether it's with words or some other supported method of communication, is there something that's bothering them, can it be fixed, and work with them to manage the agitation.

Because a lot of the times once you solve that, the agitation gets way better.

The third thing that is critical to do, and I think 1, 2, and 3 actually can and should be done in parallel, is to do something called a functional behavioral assessment or an FBA for short.

Behavioral therapists are excellent at doing this and basically what they do is they gather history from the person's parents or caregivers or loved ones or teachers or whatever and they try and observe the behavior to understand what is its function.

So, by that I mean, is the behavior serving some purpose like accessing something that the person needs or wants, escaping from something that they don't need or want, or just getting attention.

Even negative attention can be a reason for someone engaging in the behavior.

Because often, you know, if someone's having a big fit and they're agitated, like suddenly like 345 adults come onto the scene very quickly.

And what you do is you use that data and information to really think about how the person's environment, so physical environment and also interactions with the people around them, can be changed to serve that function so the person does not have to communicate that with agitation or to like remove triggers or antecedents, things like that.

So an example of that is if you learn like, oh, okay, the person is we think that they're exhibiting agitation to seek attention.

What you might do if you learn that is say like, okay, we're going to give the person attention like a comment or a thumbs up or a smile or something like that every 3 minutes at regular intervals so that they don't have to.

So, you know, you can get quite far by doing 1, 2, and 3, looking for a medical issue, supporting communication, and doing your FBA and changing the environment.

But sometimes that doesn't take you far enough.

And in those cases, that's where a psychiatric medication can be really helpful.

When I'm thinking about which medication to pick, the first thing I do is I try and think, is there a diagnosable mental health condition that could be leading to agitation and the differential diagnosis or the options are really broad and this is where meeting with a psychiatrist can be really helpful so that 1 of us can help try and understand is the person agitated because they're depressed, are they experiencing a manic episode, Are they anxious and tantruming and aggressing towards other people when they're scared and don't want to do something that's making them really nervous?

Is this an impulse control issue due to something like ADHD?

Like really trying to come to the correct diagnosis is key before prescribing a medication.

Yeah, sometimes to be honest with you we can't quite figure it out or it really seemed like there is no diagnosable mental health condition above and beyond the ASD.

And in those cases, we consider that something called irritability associated with ASD.

As we touched on before, there are 2 FDA approved medications, Aripiprazole or Abilify is the brand name, Risperidone or Risperdal is the brand name of that 1 that are FDA approved for treating these symptoms and you know what, they're incredibly effective But it's a double-edged sword because they're effective but also they can have serious side effects so that's like really like a very like personalized decision that a family and provider have to make together really thinking like you know what are the risks of using this medicine, what are the risks of not using the medicine, how long should we try it for and like really reevaluating that balance periodically.

You know, the other thing I'll mention is that oftentimes we do something called off-label prescribing which is really common and that's where we use a non-FDA-approved medication to treat irritability.

And sometimes, you know, I do start there, especially if we think that a milder medication like 1 with fewer side effects might do the trick.

It might be well worth trying a med with less side effects than risperidone or aripiprazole before going to those options.

Okay, well thank you for taking us through all of that.

Let's turn to something that you've had a lot of experience with which is comorbidities that are associated with ASD.

What are some common comorbidities with ASD and how difficult is it to differentiate these conditions from overlapping symptoms of ASD?

You know, I think the first thing I'll say is that ASD is a risk factor for almost all psychiatric comorbidities.

And I say that for a couple of reasons, the first being that, you know, as mental health providers, if you are a mental health provider, you will be treating people with ASD, even if you're not in a specialty center because the rate of comorbidity is so high.

And then on the flip side, if you're seeing someone with ASD, you should look really long and hard because more likely than not everybody, not 100%, but more likely than not there will be a psychiatric comorbidity.

So I think that's something really important to keep in mind.

You know, I would say that I have my top 3 most common.

Those would be sleep disorders, ADHD, and anxiety.

And for each of these conditions, there is, I would say, a bi-directional relationship between the comorbidity and the core symptoms of ASD and what I mean by that is like untreated comorbidity can make the ASD look worse and in a person with severe ASD it is it can be more and more tricky to decide is there a comorbidity there.

We talked a little bit about anxiety for example earlier and in a person who has more severe ASD, meaning that, you know, they have very limited ability to communicate verbally, they have more intense restricted repetitive behaviors, like more sensory issues, they really need for things to be the same all the time and have difficulty with change in routine.

Drawing the line between what is core ASD and nervousness, worry or fear about a change in routine or something that's going to be sensorally unpleasant, that bit gets really tricky.

Yeah, maybe I should talk a little bit about ADHD just because that's really common in general and definitely common in ASD.

ASD and ADHD have actually a really kind of interesting relationship and history, meaning that there was so much overlap between these 2 conditions that until recently, until the latest version of the Diagnostic and Statistical Manual of Mental Disorders, the DSM-5, was published in 2013, before that you actually were not allowed to make the comorbid diagnosis of ADHD in someone with ASD because the thought was, you know, there's so much overlap, it's impossible to draw that line, don't worry about it, it's just kind of part and partial of the ASD.

The thinking really changed around the early 2010s before

So now we are allowed to make the comorbid diagnosis of ADHD in someone with ASD.

And the reason I'm really glad that we can do that is because that then opens the door to treatment.

Because if you know providers and patients and families are thinking like, oh like you know I can never pay attention, I'm always crashing into walls, I can't sit for the duration of a short meal, but that's part of ASD.

There's nothing to be done about that that's part and parcel of my ASD.

And there are actually effective medication treatments for these really impairing symptoms of not being able to focus, stay on task, get things done, plan, organize yourself, control your impulsivity.

They're really effective treatments for these.

So I think adding on that comorbid diagnosis if it's truly there is critical.

It can be challenging though because you know hyperactivity for example that's a core symptom of ADHD but where do you draw the line because you know when we think back to like repetitive symptoms of ASD things like you know what's known as like stims like flapping or rocking or spinning like is that just repetitive movements from ASD or is that hyperactivity?

Is the person like you know crashing into walls, jumping up and down to get the sensory input they need or is that hyperactivity?

It can be really tricky to draw those lines.

It's also really common and that's an area that I think we still have a lot of work to do in, but that we've also learned a lot in the last 5 to 10 years.

I think until then anxiety was really underappreciated in people with ASD, but as we learn more, and this is actually a real research interest of mine, I think we're realizing now that it's a lot more common than we thought it was, and that it can quickly turn to other things.

Like I think we're just learning that anxiety can quickly turn to something that looks like anger, agitation, impulsivity.

So it's really important to kind of pause and think, could the person be throwing this fit, screaming, self-injuring because they're anxious, nervous, fearful of the situation.

What is Williams syndrome and how does it differ from ASD?

Can you share some of your research on this disorder?

I'm so glad that you brought this up because this is the other hat that I wear.

I'm the co-director of the Mass General Williams Syndrome Program, which is a wonderful part of my job.

Williams Syndrome is a genetic syndrome and it is caused by deletion of about 25 genes on 1 of the 2 chromosomes, 7.

It affects about 1 in 7, 000 people and it can affect really every part of the body including the brain of course.

So people with Williams syndrome generally have mild to moderate intellectual disability.

Anxiety is super common in Williams syndrome.

But I think what people with Williams syndrome are best known for is something called a cocktail personality meaning that they are very friendly, love being around people, always want to be around people.

And they're honestly just really fun to be around.

But it's a very interesting kind of compare and contrast with ASD where people with Williams Syndrome on the 1 hand are like polar opposite because they're like so socially driven but interestingly once you like peel off that surf once you peel off that initial layer and look a little bit deeper, there are some areas where people with Williams syndrome have things in common with people with autism.

So what I mean by that is people with Williams syndrome, while they have high social drive, some of their social skills are not great.

So, for example, they can make overly intense eye contact and not perhaps realize that maybe socially inappropriate or making people uncomfortable.

It's actually really scary, I think, and this is something I talk about with all my patients with Williams syndrome.

They have kids that like kind of crawl into strangers laps, like would easily go off with a stranger.

You know, I have patients that I've met for the first time in clinic and they're trying to hug me and kiss me on the very first visit, which I can assure you doesn't typically happen.

It's friendly and fun to be around, but can really put patients in danger.

The other area that is common to Williams syndrome and autism is some of these repetitive behaviors.

We actually published a paper a couple years ago showing that about 80% of people with Williams syndrome have motor stereotypies or stims, like Ron, for example.

And then another area that's of overlap between autism and Williams syndrome is this idea of having like intense, restricted, fixated, or special interests.

I would say that in Williams syndrome they're often a little bit less all-encompassing and a little bit better contained.

Like, people with Williams Syndrome don't often like open the conversation talking about, you know, whatever it is that may be really interesting to them.

But once you ask them that, they really kind of go deep on these special interests.

You know, in terms of the overlap between ASD and Williams syndrome, I think the jury is still a little bit out on that, but this is kind of how I look at it.

I would say that Williams syndrome is not protective against autism, but I don't think it necessarily increases the risk of meeting the full diagnostic criteria beyond about the 2% that we see in the general population.

And then, Can you share a bit more with us about some of your research?

As a psychiatrist, I'm very interested in brain health and mental health conditions in people with Williams syndrome.

The number 1 most common and impactful mental health condition in Williams syndrome is anxiety.

So that's really an area that I've focused on and started my research in Williams syndrome.

So some of my anxiety related studies include trying to really understand how anxiety presents in Williams syndrome.

In some ways, it's the same way that affects all of us and in other ways it can be a little bit different just because of the cognitive profile.

And I also do clinical trials trying to find effective treatments like modified cognitive behavioral therapy and testing different medication approaches for treating anxiety and Williams syndrome.

It's really important because Williams syndrome can affect the whole body and many patients for example have cardiac conditions or GI conditions to be finding medications that are really safe for their physical health as well.

And then the other area that I've gotten more interested in recently is really trying to understand what happens to the brain as people age with Williams syndrome.

It's kind of funny, Williams syndrome is a, I would say it's like a relatively young syndrome where the diagnostic test actually was not developed until 1993.

So, you know, while I definitely follow some senior citizens in my practice, people in their, you know, 50s to 70s, actually rare.

And as a field, we don't know a whole lot about what happens to people really like beyond the age of 30 to

Because if the test was only developed 30 years ago, it doesn't mean that people didn't have Williams syndrome 50 or 100 years ago, it just means that they weren't diagnosed and definitely weren't included in research studies.

You know, honestly, the state of the field is such that we're not even really able to give an accurate like life expectancy in Williams syndrome.

So, there's just so much to be learned about like what happens in your 30s, 40s, 50s and beyond.

Of course as a psychiatrist my area of expertise is really understanding what happens to the brain and how that affects emotions and behavior.

So, I'm starting to study brain aging and Williams syndrome by using neuroimaging techniques looking for and then also psychological measures and tests looking to see if there are changes in things like memory.

We really don't know if age-related brain disorders like dementia or stroke or things like that.

We don't know if they're more common, less common, or the same in Williams syndrome and how to recognize if it's happening.

See all NEI Podcast transcripts on Googlepodcasts

E184 - Autism Spectrum Disorder and Comorbidities