Clinical research is critical to advance our understanding of the causes of neurodevelopmental disorders and to develop effective treatments. The Seaver Autism Center for Research and Treatment at Mount Sinai maintains an active clinical research portfolio with a variety of recruiting studies at any given time.
Individuals on the autism spectrum as well as those with certain related genetic syndromes may be eligible to participate. The Seaver Center’s Rare Disease Program studies Phelan-McDermid syndrome, ADNP syndrome, FOXP1 syndrome, and DDX3X syndrome. Areas of focus include biomarker discovery, natural history studies, and clinical trials.
In addition to valuable contributions to science, the Seaver Center team works hard to ensure study participation is an enjoyable and low stress experience. When reflecting on their experiences, Seaver Autism Center families often recall a sense of warmth and trust.
One parent, Sakia, felt touched by how happy her son is whenever her family arrives for a visit: “As soon as he walks in, he’s running in, running into rooms, and it doesn’t bother anybody. Everyone is very welcoming.”
Paige Siper, PhD
In this Q&A, Paige Siper, PhD, Chief Psychologist of the Seaver Center, explains how research studies are conducted, the benefits of participating, and how you or someone you know can get involved.
What happens at a research study visit?
Research visits include standardized assessments administered by the clinical research team. Our multidisciplinary team spans psychiatry, psychology, and neurology, including a robust training program of psychology and psychiatry students and fellows. For idiopathic autism studies, gold-standard diagnostic testing, including the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) is administered to determine eligibility. For studies in genetic syndromes, results from genetic testing are reviewed to confirm eligibility. Most studies include cognitive and adaptive assessments. Results from clinical assessments are summarized in a research report and include personalized recommendations provided to families free of charge. Many research studies include our biomarker battery which includes electroencephalography (EEG), eye tracking and, in certain studies, brain imaging using functional magnetic resonance imaging (fMRI).
What are the benefits of participation?
In line with the Seaver Center’s mission, the goal of the clinical research program is to enhance the diagnosis of autism and related disorders, discover biological markers, and to develop and disseminate breakthrough treatments. Research participation is necessary to achieve these long-term objectives.
In addition to helping future generations through medical advancements, as mentioned above, research participants receive results from clinical testing in the form of a research report with recommendations at no cost. These reports may be used to access necessary services both within and outside the school setting.
Who can participate?
Every study has specified enrollment criteria and therefore eligibility varies by study. The Seaver Autism Center has a number of ongoing research studies and encourages you to reach out to the team to discuss studies you or your child may be eligible for.
How do you get involved?
To learn more, call the Seaver Autism Center at 212-241-0961 or email theseavercenter@mssm.edu and one of the clinical research coordinators will provide you with more information.
You may also stay in the know by signing up for the Seaver Autism Center newsletter and by following the Center on social media.
Mount Sinai’s first recipient of the National Institute of Mental Health’s T32 postdoctoral research fellowship, Training the New Generation of Clinical Neuroscientists: Vahe Khachadourian, MD, PhD.
A large body of research suggests that environmental exposures during pregnancy may be associated with autism in offspring. But those studies barely scratch the surface of the complex task of understanding the cause of autism spectrum disorders. At the Icahn School of Medicine at Mount Sinai, postdoctoral fellow Vahe Khachadourian, MD, PhD, and his mentor Magdalena Janecka, PhD, are working to solve that intricate puzzle.
Dr. Janecka is an assistant professor of psychiatry and heads the Functional Epidemiology lab at the Seaver Autism Center at the school of medicine. Dr. Khachadourian was Mount Sinai’s first recipient of the National Institute of Mental Health’s T32 postdoctoral research fellowship, Training the New Generation of Clinical Neuroscientists.
With support from this prestigious fellowship and mentorship from Dr. Janecka and others at Mount Sinai, Dr. Khachadourian is helping to paint a more complete picture of the environmental exposures that affect pregnant people and their developing children.
Pregnancy Exposures and Autism: What Is the Connection? Dr. Khachadourian trained as a physician before receiving a PhD in epidemiology. His current research focuses on the intersection of psychiatric and physical disorders — a topic that fits squarely within Dr. Janecka’s interests. “My lab is focused on early life and parental risk factors for neurodevelopmental disorders,” she said. That focus takes two tracks: “We want to learn how different exposures in pregnancy are associated with future autism risk in the child, and also better understand how different exposures in pregnancy relate to each other,” she added.
Dr. Khachadourian’s first project in the Functional Epidemiology lab focused on the latter of those goals, exploring patterns of co-occurring mental and physical health problems in a population sample of pregnant women in Israel. He found a significantly higher burden of physical problems among pregnant women with a mental health diagnosis than in those without—higher even than the rate of comorbid physical conditions, suggesting distinct links between physical and mental health during pregnancy. The physical symptoms ranged across disease states, including neurological, gastrointestinal, and musculoskeletal diseases. This work, currently pending publication, was presented at the Society of Biological Psychiatry conference last year.
The high co-occurrence of mental and physical symptoms has implications for both pregnancy outcomes and child health outcomes such as autism, Dr. Khachadourian said. In other studies, he has started to dig into the implications for autism risk. One analysis explored a variety of factors that pregnant women may be exposed to, such as preterm birth, hypoxia, infections, and trauma during pregnancy, as well as medical comorbidities, including depression, anxiety, obesity, sleeping problems, and attention-deficit/hyperactivity disorder. He and his colleagues looked for patterns among comorbidities in pregnant women and possible associations with autism in their babies. The study also incorporated data from siblings who did not have autism, to tease out which environmental exposures are most likely to contribute to the development of autism.
“If we know women have had [certain] exposures, we may be able to prevent some comorbidities, and we may be more likely to screen for and diagnose autism in their offspring earlier,” he says. “Of course, identifying these unique patterns may also help us to better understand the etiology of autism spectrum disorders.”
In other ongoing work using population samples, Dr. Khachadourian is analyzing health registry data from Denmark and Israel to examine the links between maternal medication use and psychiatric and physical diagnoses and autism in their offspring. “When it comes to autism, there are studies that have examined maternal exposures, but most have focused on one or a few diagnoses rather than systematically evaluating the wide range of diagnoses a mother can have during pregnancy. That is one unique aspect of our work,” he said. “Another aspect is that we use a relatively large sample and combine family design to try to tease out some of the confounding factors and begin to tease out some of the correlation from causation.”
These projects are exploratory in nature. While they are not designed to identify causal relationships between maternal exposures and autism, Dr. Khachadourian and Dr. Janecka hope they will point toward possible clues that warrant further study.
Fellowship Research in Functional Epidemiology The T32 postdoctoral fellowship is designed to train clinician-scientists to formulate original research questions surrounding the etiology, pathogenesis, treatment, and prevention of neurological disorders, with the goal of bridging the gap between neurobiology research and clinical disease. The structured program includes a number of core training courses and workshops, as well as a dedicated mentoring team. Ultimately, the fellowship aims to translate research into better patient care “Whenever we think about conducting a study, we always think about the implications for both clinical practice and for future research,” Dr. Khachadourian said.
The fellowship has been a rich opportunity for Dr. Khachadourian and for Mount Sinai, Dr. Janecka said, providing dedicated funding and establishing Dr. Khachadourian as an NIH-funded early-career scientist. The research has been so successful, she added, that the fellowship has been extended a third year.
That research partnership is helping to chip away at the complex factors that influence autism risk. “A lot of studies show the association of this or that with future autism spectrum disorder. But we still don’t know why,” Dr. Janecka said. “We are trying to combine several different approaches, and several different data sets, to better understand the role of the environment in autism.”
Autism spectrum disorder (ASD) is a developmental disorder. It often appears in the first three years of life and affects social communication and behavior.
Several different signs can prompt someone to seek out an autism evaluation. In this Q&A, Paige Siper, PhD, Chief Psychologist of the Seaver Autism Center for Research and Treatment at Mount Sinai, explains when you might want to seek an assessment, what that involves, and what a recent focus on sensory processing differences means.
What signs might prompt an evaluation for autism spectrum disorder (ASD)?
Several signs may prompt an autism evaluation. Concerns are commonly raised by a parent, family member, pediatrician, or teacher. Autism-specific screening should occur at the 18- and 24- or 30-month well visits and whenever a concern is expressed.
Autism is a constellation of difficulties with communication and reciprocal social interaction as well as repetitive and restricted behaviors and interests. Early signs may include delays in language or motor skills, although some individuals with autism achieve milestones on time.
Social communication signs include limited use of nonverbal communication such as eye contact, facial expression, pointing and other gestures and limited social interaction; for example, lack of showing objects of interest, minimal interest in peers or lack of shared enjoyment with others. Difficulty with imitation and pretend play are also common early signs. Repetitive behavior signs include repetitive speech, an intense focus on certain topics or parts of objects, insistence on sameness, lining up objects or toys, motor mannerisms such as hand flapping or body rocking, and unusual sensory behaviors.
Paige Siper, PhD
What are sensory processing differences?
In 2013 when the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) came out, it was the first time sensory reactivity was included within the diagnostic criteria for autism. The DSM-5 describes three categories of sensory differences:
Sensory hyperreacitivty is an overresponsiveness to sensory stimuli that may take the form of individuals covering their ears in response to sounds, squinting or avoiding the sight of certain objects, resisting the feel of certain textures or discomfort when touched by others.
Sensory hyporeactivity is an underresponsiveness to sensory stimuli, which can result in significant safety concerns. For example, an individual who is hyporeactive may not respond to the sound of an alarm, the feel of pain or temperature, or the sight of a car passing by.
Sensory seeking is an excessive interest in sensory stimuli. Individuals who are sensory seeking may repeatedly seek out the sight, feel or sound of certain objects.
Each of these examples can affect daily living and quality of life. Research suggests up to 90 percent of individuals with autism display sensory differences compared with people who do not have autism.
How do I know if my child needs a sensory assessment and what is involved?
If your child is displaying sensory hyperreactivities, hyporeactivities, or seeking behaviors that are affecting their daily functioning, a sensory assessment may be warranted. The goal of a sensory assessment is to identify personal sensory preferences. We all have our own sensory preferences, and by determining those preferences we can modify environments accordingly.
Over the past several years, the Seaver Autism Center at Mount Sinai developed a novel sensory assessment called the Sensory Assessment for Neurodevelopmental Disorders (SAND). The SAND combines a semi-structured, clinician-administered observation and a corresponding caregiver interview. We want to see, within an exam setting, how a child responds to stimuli that prompt sensory responses, and we also want to capture information from caregivers about their child’s daily experiences.
Following an assessment, parents will learn about their child’s unique sensory preferences and sensitivities, and then an individualized treatment plan can be developed and implemented. Adjustments in an individual’s sensory experiences can have a profound impact on adaptive behavior, social engagement, and learning.
Since autism is a lifelong diagnosis, how can parents and caregivers support their child as they develop?
Parents are their child’s greatest advocate and the true experts. Parents can support their children by helping them develop the skills necessary to become as independent as possible. A variety of interventions are commonly used to help individuals on the autism spectrum gain skills. These include:
Applied behavior analysis, often referred to as ABA therapy, is one evidence-based treatment for core features of autism.
Speech and language therapy is important to develop both functional and pragmatic communication skills.
Occupational therapy can focus on sensory reactivity, fine motor skills, and activities of daily living.
Physical therapy can target challenges such as low muscle tone, which is commonly observed in autistic individuals.
It is important for each child to have a personalized treatment plan that is reviewed and updated regularly to ensure individuals reach their optimal potential.
What programs and services does Mount Sinai offer at the Seaver Autism Center?
The Seaver Autism Center is a multidisciplinary program with a large research focus ranging from natural history studies that track change over time to clinical trials that test new treatments. All individuals participating in research at the Center receive an autism-focused research evaluation. We also offer neuropsychological and psychoeducational evaluations, individual psychotherapy for those on the autism spectrum and their siblings, parent training, and medication management through Mount Sinai’s Faculty Practice Associates. The Seaver Autism Center has a large community outreach program that offers social skills groups and training for both families and professionals. We have a variety of collaborations with local cultural institutions such as the American Museum of Natural History and the Guggenheim Museum. Finally, our training program is committed to training the next generation of autism experts.
What is the Seaver Autism Center at Mount Sinai doing to support patients’ sensory needs?
Over the past year, we made it a priority to improve care and better support individuals on the autism spectrum’s sensory needs within the Mount Sinai community. We developed Sensory Toolkits that are now available within our pediatric emergency departments. We are starting to disseminate the toolkits to other specialized practices within and outside of the Health System with the goal of improving the patient experience. Each kit has several sensory tools, as well as an information sheet that explains the intended use of each tool to satisfy sensory needs and ultimately to make each person’s experience more comfortable. Families get to take the kits home with them to continue using beyond their visit to Mount Sinai. Our team also developed a learning module, now available across the Mount Sinai Health System, to train physicians, clinicians, and staff members within different disciplines on how to best support neurodiverse patients. We are actively collecting data on both of these initiatives to ensure these new programs are serving their intended purpose. Finally, we are surveying caregivers of children on the autism spectrum to determine which sensory interventions and supports have and have not worked for their child. You can learn more here.
The Seaver Center for Autism Research and Treatment at the Icahn School of Medicine at Mount Sinai is advancing the understanding of autism spectrum disorder.
Autism spectrum disorder (ASD) is increasing in prevalence, but so are options for evaluation and therapies, said Paige Siper, PhD, Chief Psychologist for the Seaver Autism Center for Research and Treatment, and Michelle Gorenstein, PsyD, Director of Outreach for the Seaver Center. “The interesting and exciting part about the work that we do is that we get to see toddlers through adults, and I think that is something very unique about this field,” said Dr. Siper, Assistant Professor of Psychiatry, Icahn School of Medicine at Mount Sinai. The virtual talk can be viewed here.
Paige Siper, PhD, Chief Psychologist of the Seaver Center
“Autism Spectrum Disorder Across the Lifespan” was hosted by the Mount Sinai Office for Diversity and Inclusion. It was part of a series featuring speakers from around the Mount Sinai Health System as well as the community to raise awareness and promote an inclusive and equitable health care environment for people with disabilities.
Dr. Gorenstein, Assistant Professor of Psychiatry, Icahn School of Medicine, said that an important tool in the field is Applied Behavioral Analysis, a class of interventions based on principles of operant learning theory—that is, providing positive reinforcement for observable behavior, like asking for a push on a playground swing, or making a choice. Another therapy, Relationship Development Intervention, is a family-based method that builds social and emotional skills. And there are a variety of therapies to treat conditions that can accompany ASD, such as anxiety, ADHD, or epilepsy.
Michelle Gorenstein, PsyD, Director of Outreach for the Seaver Center
ASD is characterized by difficulty with social communication, as well as the presence of repetitive behaviors or restricted interests. ASD is primarily a genetic disorder but can also be influenced by environmental factors. Dr. Siper said multiple studies have shown that vaccines do not cause ASD, dispelling a common myth.
One in 54 children in the United States are diagnosed with ASD, and boys are four times more likely than girls to receive the diagnosis. ASD can be identified in children as early as age 18 months, which makes early intervention very important in improving social, communication, motor, and daily living skills. “Early intervention can change outcomes,” Dr. Siper said. “It’s the opposite of watch and wait.”
The Seaver Center is dedicated to caring for people of all ages with ASD, furthering research into risk factors and drug development, and leading clinical trials. “One of the unique things about our Center is that it really does translate the basic sciences to the clinic,” Dr. Siper said. For more information, visit the Seaver Center site.
Additional disabilities-related resources are available on the Mount Sinai Office for Diversity and Inclusion site.
Sandra Sermone and her son, Tony, who has ADNP syndrome. Mrs. Sermone founded the ADNP Kids Research Foundation, which is funding Mount Sinai’s phase 2 clinical trial into the safety and efficacy of ketamine as a potential treatment.
Ketamine, an anesthetic medication that has also been approved for use in severe depression, is now offering promise to children with a form of autism known as ADNP syndrome, or Helsmoortel-Van Der Aa syndrome. Ten children, ages 5 to 12, will soon take part in a clinical trial conducted by the Seaver Autism Center for Research and Treatment at Mount Sinai to determine whether ketamine is safe and well tolerated, and able to help compensate for the neuropsychiatric deficits that stem from missing a copy of the ADNP gene.
This will be the first clinical trial launched for ADNP syndrome, which was identified in 2015. It is a testament to the dedication of parents and physicians at the Seaver Autism Center, and the potential of artificial intelligence (AI) in helping advance treatment research in rare disorders.
Ketamine and several other existing drugs were identified by an AI tool, mediKanren. It was created at the University of Alabama by a colleague of Matthew C. Davis, MD, whose child has ADNP syndrome. Dr. Davis and another parent, Sandra Sermone, investigated ketamine in relation to ADNP within the existing scientific literature and found that it upregulated expression of the gene. With this and other relevant clinical data in hand, they filed for intellectual property protection. Then Mrs. Sermone brought the information to leaders of the Seaver Autism Center, who agreed that it was worth further investigation. Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center applied to the U.S. Food and Drug Administration for permission to proceed with a clinical trial and received approval.
“We think ketamine has potential and that it’s safe, so we’re very excited about it,” says Mrs. Sermone, who founded the ADNP Kids Research Foundation in 2016. The Foundation recently ran a “virtual” fundraising effort that raised more than $150,000 in six weeks that will be used to finance the entire phase 2 clinical trial and begin to lay the groundwork for a possible phase 3 study.
Approximately 275 children worldwide have been diagnosed with the syndrome, which often is accompanied by other complex health issues of the heart and brain. “I am so grateful for the team at Mount Sinai. I’ve never seen a group more dedicated to working with patient groups,” she adds. “Ketamine is a repurposed drug, so if it shows efficacy we can hopefully move quickly into a larger, phase 3 clinical.”
Ana Kostic, PhD, Director of Drug Discovery and Development at the Seaver Autism Center, says, “Ketamine has been used for many decades. We know a lot about the molecule and its safety profile, and now to find new uses for it through scientific discovery is amazing.”
Since ADNP is very important for the development and function of the central nervous system, the ability to restore its functionality would be extremely beneficial.
Dr. Kolevzon says each of the children enrolled in the clinical trial will receive a single infusion of ketamine over a period of 40 minutes and will be monitored over the course of four weeks to assess improvement. In addition to determining its safety and tolerability, he says, “we are also really interested in clinical improvement. Kids with ADNP have a lot of sensory sensitivities that we can measure with different tools, such as electrophysiology.” This would enable the researchers to “see whether there are changes in the electrical patterns in the brain in response to ketamine, and that might give us insight into potential biomarkers. These children have language problems, behavioral problems, and sleep problems. There are a lot of issues that go along with ADNP syndrome that we’re hoping to potentially address.”
The promise of ketamine may also extend to larger populations of individuals with autism who do not necessarily have ADNP syndrome, according to Dr. Kostic. “It could have beneficial effects in people who don’t have the same mutation but who have similar deficits.”
Access to high-quality genetic technology has become increasingly affordable over the past several years and has enabled more families to receive accurate and earlier diagnoses of many disorders, including autism. In most cases, the younger a child receives intervention, the better their chances of improvement. Earlier diagnoses, and a potential treatment such as ketamine, provide Mrs. Sermone and other committed parents with hope.
“It’s incredibly important because, currently, there isn’t one single treatment for our children with ADNP syndrome,” says Mrs. Sermone. “Our kids don’t produce enough of the ADNP protein. It’s like they’re running on half a tank of gas. To improve the quality of their lives—for us, that would be amazing.”
Children who have older siblings or frequent interaction with grandparents are diagnosed with autism spectrum disorders (ASD) earlier than those who do not, according to new research conducted at the Seaver Autism Center for Research and Treatment at Mount Sinai, and published in the journal Autism.
The study, titled “Grandma Knows Best: Family Structure and Age of Diagnosis of Autism Spectrum Disorder,” found that about 50 percent of friends and family members reported they had suspected a child to have a serious condition before they were aware that either parent was concerned. Maternal grandmothers and teachers were the two most common relationship categories to first raise concerns. “Our work shows the important role that family members and friends can play in the timing of a child’s initial diagnosis of autism,” says Joseph D. Buxbaum, PhD, the G. Harold and Leila Y. Mathers Research Professor, and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience, Icahn School of Medicine at Mount Sinai, and Director of the Seaver Autism Center. He is senior author of the paper, which was published online February 8, 2017. The study included colleagues at Columbia Business School and Carnegie Mellon University.
The team conducted an online survey of 477 parents of children with autism. In addition, they carried out novel, follow-up surveys with 196 “friends and family,” who were referred by parents. Eighty percent of the children with ASD were boys, and the median age of diagnosis was 33 months. Frequent interaction with a grandmother reduced the age of diagnosis by 5.18 months, and frequent interaction with a grandfather reduced the age of diagnosis by 3.78 months. “Since early detection of ASD is critical to effective treatment interventions, we hope the study will serve as a call to action to encourage family and friends to share concerns early on,” Dr. Buxbaum says.
In other news, the Autism Sequencing Consortium, a multi-institute research group founded by Dr. Buxbaum, has received a $7 million extension of a grant from the National Institutes of Health to collect, analyze, and share samples and genetic data from people diagnosed with autism.
The Consortium now includes more than 40 international groups and 150 researchers who have generated gene sequencing data from 29,000 individuals, making it the largest such study to date in autism. All shared data and analyses are hosted on a supercomputer called Minerva, designed by Mount Sinai faculty, which enables joint analysis of largescale data. The new grant will extend the project through 2022 and expand the sample to include more than 50,000 individuals.
