Spectrum: Autism Research News

Francesca Happe

Professor of Cognitive Neuroscience, King’s College London

President, International Society for Autism Research (INSAR)

Global access: “The standout talk for me was [Maureen Durkin’s keynote] this morning, highlighting the need for a more global effort in autism research. Of course we’re aware already of the discrepancies in wealth and welfare across the world that affect autism recognition and intervention. But I thought her message — about the importance of free diagnostic resources and the need for the community to involve as many people and countries as possible — was especially inspirational. I think creating a platform that helps facilitate open sharing of measures is something INSAR might be able to spearhead.

“In particular, I appreciated her quote: ‘Getting an autism diagnosis is like a new technology, and it’s not available to everybody.’ Can we do the equivalent of creating a really cheap mobile phone that’s solar powered, or developing devices that can purify water on-site without electricity; you know, all these wonderful innovations that have made technology available to the developing world? What’s the equivalent in autism diagnosis and intervention? Not the quick fix, but what’s the really clever innovation that will revolutionize access?”

Presidential priorities: “[As the new president of INSAR], I think our becoming a truly international society has to be a high priority. The free flow of information internationally is something that we can champion. I think there’s also a lot we can do for students and training. We’d like to revisit the idea of an INSAR summer institute to create a platform for early-career clinicians and students to interact with experts in the field. Taking part in the ‘meet the experts’ lunch was a highlight of my IMFAR this year!

“I also think there’s a real role for us to help bridge the gap between scientists and families. Just as people who are clinically grounded get to learn about the new technologies and cutting-edge scientific analysis, I feel it’s important for researchers working with the data to get to see what autism really is, and learn what people with autism really want. I think developing programs to facilitate that dialogue will be really exciting.”

Lauren Adamson

Regents’ Professor of Developmental Psychology, Georgia State University

Minimally verbal across disciplines: “I found the sparks of insight at the early-morning meeting of the new special interest group on minimally verbal individuals truly energizing. There is now a critical and growing mass of both junior and senior scientists dedicated to research focused on the substantial number — perhaps 25 percent to 30 percent — of individuals with autism who do not acquire functional language by school age.

“These researchers are not shying away from fundamental questions about definition (What does it mean to be nonverbal?), assessment (How can we look beyond standardized assessments to discern if language use is functional?) and intervention (What treatments might work best for which individuals?). It is especially heartening that researchers are increasingly working across institutions and disciplines to seek innovative answers to these questions.”

Irva Hertz-Picciotto

Professor, University of California, Davis MIND Institute

A surprising result: “From Paul Patterson, that a bacterium (Bacteroides fragilis) introduced into a pregnant rodent in an induced inflammatory state corrects several of the autism-like symptoms in offspring, restoring their exploratory behaviors, etc., though not their social deficits.

Big picture: “The microbiome may exert a really potent influence on neurodevelopment —the world of the microbiome begs for a wide range of research.”

Matthew Mosconi

Assistant Professor, University of Texas Southwestern Medical School

A refreshing trend: “The educational symposium on the cerebellum was a nice change of pace, demonstrating some renewed interest in understanding the role of this structure in ASD. Histopathology studies have consistently implicated the cerebellum for years now, but this is a uniquely interesting structure that probably has not received the attention it deserves in ASD research.

“Catherine Stoodley’s discussion of the broad functions of the cerebellum, including its role in supporting sensorimotor processes, cognitive systems, language and affective systems — and the cerebellum’s distinct circuits dedicated to these functions — presented a superb context for the rest of the talks. Mustafa Sahin laid out a nice case for focusing on the role of the cerebellum in tuberous sclerosis complex, and using these studies as a model for understanding ASD.”

Need for sameness: “I was able to be part of one of the scientific panels this afternoon discussing studies of the need for sameness in ASD. These studies examined repetitive behaviors at the neuropsychological, neural systems and genetic levels, so it was really an attempt to develop a cohesive story based on work we have been doing collaboratively for the past five-plus years as part of our Autism Center of Excellence, directed by Ed Cook.

“Mike Ragozzino, Chris Mueller (from Jeremy Veenstra-VanderWeele’s lab) and Jim Sutcliffe presented really elegant studies that I think lead us in novel directions. I do think that this type of approach — developing parallel patient and preclinical studies — is moving us toward drug discovery and making some sense of one of the few biomarkers that has been identified: hyperserotonemia.”

Lawrence Reiter

Associate Professor, University of Tennessee Health Science Center

True systems biology: “Dan Geschwind’s keynote address was outstanding. It’s remarkable that Dan has been able to convey the complexity of the underlying genetics of autism in the context of regional gene expression. Although the term has been used ad nauseam, Dan’s approach to autism is truly a systems biology view, which includes human genetics and human biospecimens as well as animal models and cultured neurons.

“He has managed to find a way to focus not on a single autism-associated gene but on all of the autism-associated transcripts simultaneously, by placing these gene expression networks into regional, developmental and disease-associated convergent networks.”

Also worth mentioning: “I also found interesting today a poster by William Gaetz and his collaborators using 1H-magnetic resonance spectroscopy to visualize changes in GABA brain metabolites in vivo, as well as several talks on new animal models using a variety of chromosomal engineering methods (16p11.2 copy number variations) and Cre/Lox cell-type-specific knockouts (TSC1 mutant mice).”

Lowlight: “The free convention center lunch is always a bad idea — even in Spain.”

Hilde Geurts

Professor of Psychology, University of Amsterdam

Considering comorbidities in the clinic:
“We were discussing [Thursday’s keynote by Christopher Gillberg] during the student expert lunches, [considering how his message] could or should change our work. His call to focus on all kinds of comorbidities is good to stress once more for research, but also for clinical practice.

“We feel that it is important to take comorbidities into account and not view a diagnostic category as something static. This mainly means that you can still focus on autism, but that you should not put all your energy into looking for individuals with autism without any comorbidities.”

David Ledbetter

Executive Vice President and Chief Scientific Officer, Geisinger Health System

Not just autism: “I loved Christopher Gillberg’s keynote address this morning on ESSENCE. I had never heard him speak and only recently became aware of his extensive research and publications on autism as part of a broad spectrum of neurodevelopmental disorders (including attention deficit hyperactivity disorder [ADHD], developmental coordination disorders, intellectual disabilities, schizophrenia and others).

“His astute clinical observations and studies document the high frequency of comorbidity across this wide spectrum, such that it is hard to find examples of ‘pure autism’ or ‘pure ADHD’ without other neurodevelopmental features. He was very provocative in cautioning against too much focus on ‘autism only’ as a subject of research.

“Our group has recently published similar observations of shared genetics across multiple neurodevelopmental phenotypes, which we call developmental brain dysfunction, or DBD — very similar to ESSENCE.”

More research needed: “Gillberg’s estimate is that as much as ten percent of children under 18 years old fall into this broad category of developmental disorders called ESSENCE — a major public health issue. Many questions arise as to the most efficient way to identify these children as early as possible and to intervene and optimize outcomes.

“We have not emphasized the overlap of DBD with ADHD as much as Gillberg does with ESSENCE, so we need to reconsider how we include that in our clinical research designs and patient recruitment and assessment.”

Stephan Sanders

Postdoctoral Associate, Yale University

Important threads from today: “A series of talks at IMFAR today has made me consider my approach to autism diagnosis, both as a physician and as a researcher. In the keynote, Christopher Gillberg raised the importance of considering [autism spectrum disorder] in the context of other neurodevelopmental disorders (the ESSENCE model), suggesting that the overlap with ADHD, Tourette’s and even schizophrenia is a sign of shared etiology.

“In the following session, John Constantino presented their latest work with the Interactive Autism Network, assessing how many diagnostic categories (or ‘factors’) best captured the complexity of autism diagnosis, as measured with the Social Responsiveness Scale. This study showed that five factors was the best fit, rather than the two described in the DSM-5 (i.e., social communication and repetitive or restricted behaviors and interests).

“Finally, work from Stelios Georgiades in Toronto used a similar approach with the Autism Diagnostic Interview-Revised and showed that while three factors best describe autism at diagnosis, by the age of 6, two factors fit better.”

Data-driven diagnosis: “Taking these three talks together makes me imagine the future of autism diagnosis. They point toward neurodevelopmental disorders being treated as a single etiological entity, with subdivisions driven by age-specific phenotype data rather than strict diagnostic criteria. The findings from genetics studies are pointing in this direction, with overlap seen between intellectual disability, autism, Tourette’s, ADHD, epilepsy and schizophrenia.

“At present, we see poor correlation between specific genetic risk factors and phenotypes. Might a data-driven phenotype definition perform better? Importantly, this approach may also be of utility for choice of therapeutics. This would require a more complex view of study recruitment — for example, that the Social Responsiveness Scale is as important as the EEG in epilepsy and conversely that the EEG is as important as the Social Responsiveness Scale in autism.

“Without considering how these phenotype measures overlap across these disorders, and how they change with time in individuals, it is hard to imagine building a sufficient model of neurodevelopmental dysregulation to guide future studies and therapeutics.”