The Waisman Center’s signature research project looks deeply at the connections between autism and ADHD

Signature Research Project Looks Deeply at the Connections Between Autism and ADHD

By Emily Leclerc, Waisman Science Writer

Note: Both the Travers Lab and Li Lab use identity-first language in response to the growing preference for that language in the autism community. Josh however still prefers to be referred to as a person with autism so person-first language will be used when referencing Josh.

Josh loves coming to the Waisman Center. He has told his mom Julia several times that he particularly enjoys the two-day visits because he gets to spend more time at the center. His brain is special so it is cool that the scientists want to study it, he tells Julia. Alongside participating in research studies, Josh also has big plans to put together a reading nook underneath the front stairs at the Waisman Center so research participants can have a quiet place to read in between appointments.

Josh, who is seven, was diagnosed with autism and ADHD at the Waisman Center and continues to be seen in the Autism and Developmental Disabilities Clinic. Currently, he is participating in the signature research project of the Waisman Intellectual and Developmental Disabilities Research Center (IDDRC) grant.  The study is called the University of Wisconsin Longitudinal Imaging and Neurogenetics in Kids (UW LINK) Study. It is led by James Li, PhD, a Waisman investigator and associate professor of psychology, and Brittany Travers, PhD, a Waisman investigator and associate professor of kinesiology. The IDDRC “center” grant requires a multi-disciplinary program of intellectual and developmental disabilities (IDD) research and supports core facilities which are utilized by other IDD research projects.  A second requirement of the center grant is a signature research project in IDD.

James Li, PhD
James Li, PhD

The UW LINK Study is seeking to learn more about co-occurring autism and ADHD in order to facilitate more precise diagnoses and better, more effective treatments for kids like Josh. “I think that this research, especially knowing the genetic link, is important. I think just understanding how the brain works, how it works differently, and how we can help [people with autism and ADHD], especially as kids when their brains are growing and developing, is important,” Julia says.

It is estimated that between 30 and 75 percent of kids with autism also have symptoms of ADHD. But despite there being such a high prevalence of co-occurrence, not much is currently known about how the two conditions impact each other. What is known is that kids with both autism and ADHD are more likely to have lower IQs, poor daily living skills, more pronounced autism features, and are more likely to be prescribed psychotropic medications that do little to treat either autism or ADHD. Additionally, there are currently no evidence-based psychotropic or psychosocial interventions and treatments for kids with co-occurring autism and ADHD.

In part, the reason that so little is known about these two conditions together is that kids could not be diagnosed with both autism and ADHD until 2013 when the Diagnostic and Statistical Manual of Mental Disorders (DSM) was updated to allow for a co-occurring diagnosis. Before 2013, if a child was diagnosed with autism, they could not also be diagnosed with ADHD and vice versa. That overlap was not allowed even though the scientific community agreed that not only was it possible to have both autism and ADHD, it could also be debilitating.

But largely the reason behind the limited knowledge is that the cause and underlying reason or reasons behind co-occurring neurodevelopmental conditions is not well understood. Before better diagnoses and more effective treatments can be developed, the foundation of basic science has to be laid. So, to address these gaps and provide the fundamental information needed to better help kids with autism and ADHD, Li and Travers developed and designed the UW LINK Study as a large longitudinal investigation into the biological underpinnings of co-occurring autism and ADHD. “It seems like there has to be some type of biological aspect to this that we can hope to better understand through this project. Then we can better conceptualize what is co-occurring autism and ADHD and also hopefully have targets to be able to think about whether there are ways we can ameliorate some of those features,” Travers says.

When designing this study, Li and Travers purposefully integrated aims to broadly study co-occurring autism and ADHD to not only collect as much information as possible but also fulfill the requirements of the center grant that the project is encapsulated under.

Brittany G. Travers, PhD
Brittany G. Travers, PhD

When Waisman was reapplying for their core grant, it also required that a research project be a part of the application. Li and Travers’ UW LINK Study was chosen because of how it utilized the breadth of resources available at the Waisman Center. “The way our signature research project had to come together was it needed to tap into multiple resources and facilities at the Waisman Center. Because this is a center grant, you have to leverage the resources of your center,” Li says. “It is on a much bigger, wider, broader scope than an individual grant would be.”

The highly collaborative nature of this study lends itself particularly well to the Waisman Center where all of the necessary resources are housed under one roof. The UW LINK Study not only takes advantage of the wide array of expertise that Waisman holds but all of the facilities that Waisman has built to provide for its researchers. “People I don’t get to collaborate with very often, we come together and all focus on this issue of autism and co-occurring ADHD from a behavioral perspective, genetics perspective, brain imaging perspective, neuronal perspective, a more holistic perspective, and a developmental perspective,” Travers says.

In pursuit of the goal of understanding co-occurring autism and ADHD, Li and Travers created four objectives for the study. The first is data collection, the second is developing stem cell lines, the third is analyzing genetic information, and the fourth is combining the data from the previous three aims into a machine learning model that will hopefully be able to predict outcomes.

ClipboardThe first aim is the most extensive, requiring participants to provide a vast amount of information. Participants receive an extensive psychiatric assessment that looks at the whole gamut of mental health functioning. A saliva sample is taken for genotyping. Every participant undergoes an MRI (magnetic resonance imaging) brain scan. Josh says that getting an MRI is not his favorite part of the day but that he’s okay being in there and finds it interesting to watch. Then neuropsychiatric tests – like IQ, working memory, and processing speed – are conducted and the participant and their family fill out multiple questionnaires about environment, family, peers, and quality of life. These data are collected every year for a total of five years. Additionally, a select number of participants also provide a blood sample once in order to establish a stem cell line.

“That’s really the innovation of this study. We are not only collecting all of this data on a fairly unique population because we are actually focusing on comorbidity, but we are also doing it over time with the same kids,” Li says.

NeuronThe second objective of the study uses stem cells collected from the blood samples to grow neurons. These stem cell models will be used to hopefully illuminate potential molecular mechanisms that underlie the behavioral differences seen between kids with autism and ADHD and kids with only autism. The stem cell stage will be handled by another Waisman investigator on the grant, Xinyu Zhao, PhD, a professor of neuroscience.

DNAIn order to analyze the genetic information from each participant for objective three, researchers will use the information gathered from blood samples along with publicly available genome data to look for what is unique about the genome of someone with autism and ADHD in comparison to someone with only autism. “Presumably there will be specific or unique genes for either condition in which individuals who have both conditions carry,” Li says.

ResearchThe study’s final goal is to compile all of the data collected and use it to build a machine learning model. This large-scale look at co-occurring autism and ADHD across all of these perspectives will hopefully provide novel insights into the reasons behind the high prevalence of co-occurrence. “Basically, you just throw in every single variable that you’ve collected; imaging, phenotyping, psychiatric outcomes, genomics, stem cell data, and more. It’s called multidimensional. Once compiled, our machine learning expert, [Daifeng Wang, PhD, Waisman investigator and associate professor of biostatistics and medical informatics, computer sciences] will create a model that can predict outcomes,” Li says.

Autism or ADHD on their own can have significant impact on someone’s life but when they happen together the effect can be detrimental. Josh and Julia have experienced many of the hardships that can accompany this duel diagnosis. She is appreciative that Waisman researchers are taking the time to ask these questions and investigate further.

Ultimately, Li and Travers’ goal is to lay a solid foundation on which new and more effective treatments can be built. “There aren’t great treatment recommendations for autism and ADHD and what is available doesn’t work well either. So, I would love for us to be able to identify, through the work we’re doing, some specific cognitive interventions that might be more useful for autistic kids with ADHD,” Li says. And if Li and Travers themselves don’t move into treatment and intervention work, the data collected will be available to other researchers to bolster their path forward.

At the moment, the UW Link Study is fully underway and is in the midst of collecting its second year of data. There is still a long way to go in the study and a lot left to do but Li and Travers are excited to see where it will lead. Josh is also excited but more about the prospect of spending time at the Waisman Center and in his future reading nook than the study itself. His mom Julia is grateful that the study has the potential to impact kids with autism and ADHD far into the future and help more kids like Josh.

“We feel like this runs in our family,” Julia says. “We can see the characteristics in adults [in our family] that are undiagnosed. We feel like it is important for future research and for our future family members that this research is done to better understand how to support people with autism and ADHD because childhood can be very challenging for them.”