The soggy start to last year’s inaugural Eagles Autism Challenge didn’t keep more than 3,000 cyclists, runners, and walkers from joining the cause to raise funds for innovative research and programs to learn more about autism spectrum disorder (ASD). If participants minded the rain, you couldn’t tell from the smiling faces peeking from under hoods and hats.
The Challenge raised $2.5 million to address the complexities of autism through collaborative research among founding beneficiary partners Children’s Hospital of Philadelphia, Drexel University, and Thomas Jefferson University and Jefferson Health. These organizations aim to share their discoveries to advance autism research in Philadelphia and around the world.
Putting the event goals into action, the Eagles Autism Challenge recently awarded $936,000 to CHOP researchers to support three clinical research projects. All submitted proposals were reviewed by a distinguished scientific peer review panel and evaluated for potential for measureable outcomes and impact in the field of autism research. Each of the funded projects at CHOP seek to clarify the interplay of autism and co-occurring conditions.
As participants gear up and excitement builds for this year’s Challenge, happening May 18, Cornerstone spoke with the principal investigator from each project to learn more about their work.
Autism and Epilepsy
William Gaetz, PhD, a research scientist in the Department of Radiology at CHOP, is leading a study to investigate implications of specific neurological pathways in the connection between ASD and epilepsy. While large-scale prevalence studies consistently show that ASD and epilepsy co-occur, the biological mechanisms underlying this comorbidity remain unclear.
“We plan to explore epilepsy comorbidity in children with autism using two separate neuroimaging methods: magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS). MEG is ideally suited for detecting atypical (i.e., epileptiform) electrical responses in the brain, while MRS provides a measure of chemical neurotransmitter concentrations that might underlie atypical brain signaling,” Dr. Gaetz said.
Together, these measures will help Dr. Gaetz and his colleagues assess whether similarly atypical electrophysiological patterns in ASD represent a biologically meaningful subgroup. If so, such stratification might represent a new target for therapeutic interventions.
Utilizing MRS, Dr. Gaetz and his team have previously shown that gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, is reduced in the brains of children with ASD. In separate studies, they have also used MEG to show that brain responses to tactile stimulation are reduced for both children with ASD and in children with epilepsy, and these responses originate from brain regions where GABA levels are reduced; thus, the speculation that reduced MEG responses may be due to low GABA concentrations.
“This grant will allow us to extend our prior findings and assess whether these observations are related by a common mechanism in children with both ASD and epilepsy,” Dr. Gaetz said. “For example, we predict that for individuals with relatively low GABA levels, we may not only see reduced somatosensory responses, but also more epileptiform activity.”
Prior studies have shown that for children with ASD and comorbid epilepsy, the rate of epilepsy increases as IQ decreases. This study will enable the characterization of the neural correlates of atypical epileptiform comorbidity in children with ASD. The researchers anticipate a subset of children with ASD will show significant epileptiform discharges when observed in resting MEG which may be predicted by reduced GABA levels. This observation could represent an opportunity for stratification within the spectrum.
“Observing such a subgroup might shed light on common mechanisms, and thus represent a potential target for intervention,” Dr. Gaetz said. “For example, the repurposing of anti-epileptic medications for children with ASD and significant epileptiform activity may improve ASD symptoms as well as cognitive processes such as learning, memory, and IQ.”
Autism, ADHD, and Anxiety Disorders
John Herrington, PhD, a psychologist in the Department of Child and Adolescent Psychiatry and Behavioral Sciences at CHOP, is pursuing a project focused on ASD and co-occurring attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders.
“We have grown increasingly aware that ASD truly is a spectrum — one that includes a number of dimensions and characteristics that have previously gone overlooked and understudied,” Dr. Herrington said. “This is particularly true of psychiatric symptoms such as anxiety and ADHD, which affect nearly half of all individuals with ASD, but are not part of the ASD diagnosis itself.”
Anxiety and ADHD symptoms are sometimes reported to be as problematic to affected individuals as the symptoms of ASD. And yet, according to Dr. Herrington, research and treatment are behind in developing tools to measure and track anxiety and ADHD symptoms in ASD. The goal of this proposal is to advance several innovative methods for assessing anxiety and ADHD symptoms that place relatively few demands on verbal communication, and are therefore usable across a spectrum of ability in ASD.
“Biomarkers of Co-occurring Psychiatric Symptoms in Children With ASD” involves innovative approaches to collect information about the psychophysiological markers of stress and anxiety, and computer vision-driven measures of emotional expressiveness.
“Both of these approaches involve very recent technological advances, such that the project would have been infeasible even a few years ago,” Dr. Herrington said.
Additionally, study participants will bring devices home that can measure their heart rate and cameras that can measure their facial expressions during a social interaction. This is a priority of the study, as symptoms of anxiety and ADHD are often more prominent in the home setting. The proposed project will ultimately examine the reliability of a computerized assessment that may eventually augment existing paper-and-pencil measures of ADHD symptoms.
Dr. Herrington’s team includes CHOP and Center for Autism Research (CAR) faculty Benjamin Yerys, PhD, leading the ADHD arm, and Julia Parish-Morris, PhD, a CAR expert in computational linguistics. They are developing and piloting the methods for the study to begin data collection this summer. A key goal is to confirm participants will be able to readily follow the procedures in their homes without hands-on expert guidance. Ultimately, they aim to develop the next generation of tools that can help better track the often debilitating symptoms of co-occurring psychiatric disorders in ASD.
“These tools could eventually help us identify and treat these symptoms among individuals who often have difficulty verbalizing their distress,” Dr. Herrington said. “A further goal is to develop better outcome measures for the treatment of these symptoms, which in turn will lead to better treatments.”
Family Navigator for Autism
Nathan Blum, MD, chief of the Division of Developmental and Behavioral Pediatrics, and his team will use the Eagles Autism Challenge award to build upon previous research into approaches to help support families of children with ASD and comorbidities such as language disorders, challenging behaviors, anxiety, ADHD, sleep problems, and epilepsy. The study will evaluate the effect of a family navigator on increased access to care and participation in community-based behavioral health services.
“Many families with a child with autism struggle to manage the child’s challenging behavior,” Dr. Blum said. “Sometimes the challenges seem to relate to accessing appropriate school and community-based services and at other times, the behaviors persist despite the fact that the child has accessed available services. We want to assess whether we could develop a tiered intervention that would be both efficient and effective in helping these families.”
The proposal for “Assessing the Efficacy of Family Navigation and Interprofessional Care of Challenging Behaviors in Children With Complex Autism Spectrum Disorder” notes how CHOP is uniquely positioned to assemble an interprofessional team to try novel approaches to develop the community-based collaborations needed to improve functional outcomes through support and treatment for families and children living with ASD and its comorbidities.
The main goal of the study is to develop and test the family navigator intervention aimed to improve access to community-based behavioral health services and encourage continued participation.
“We are adapting the family navigation role to specifically focus on helping families of children with ASD and disruptive behaviors,” Dr. Blum said. “In addition, we are using a sequential multiple assignment randomized trial design which accurately reflects the process of clinical decision-making.”
The research team will then run a preliminary comparative efficacy study comparing the family navigator intervention versus standard care and their effects on reported difficulties for families of children with ASD.
“If our approach is successful, we may learn more about how to tailor interventions to best address the needs of children with ASD and disruptive behaviors and their families,” Dr. Blum said.
In a separate aim, researchers will also collect saliva samples to help populate the Eagles Learning Health System biorepository.
“We expect that the infrastructure built, and pilot studies conducted, during the first two years of this program will serve as the foundation for an ongoing clinical research program that will transform the experience of children with ASD and their families in the Philadelphia region and contribute to an evidence-base that will serve to transform care nationally and internationally,” Dr. Blum and his team stated in their project proposal.
Interested in making an impact on the next round of awards to further knowledge about autism? It’s not too late to register for the 2019 Eagles Autism Challenge. Participation by cycling, walking, running, or making a donation helps deliver necessary resources to the field of autism research.
(Support Team CHOP in Eagles Autism Challenge May 18: It’s not too late to support your CHOP colleagues and patients participating in the Eagles Autism Challenge May 18! Make a donation to any member of Team CHOP, and help reach the goal of raising more $2.5M for autism research and care.