Neurobiology of Autism Spectrum Disorders

November 10 - 18

 

Coordinator: Randy D. Blakely

Vanderbilt University, Nashville, USA

 

Faculties:

Catalina Betancur, Université Pierre et Marie Curie, Paris, France

Pat Levitt, University of Southern California, Los Angeles, USA

Declan Murphy, Institute of Psychiatry, London, UK

Antonio M. Persico, University Campus Bio Medico, Rome, Italy

Craig Powell, University of Texas Southwestern Medical Center, Dallas, USA

Jeremy Veenstra-VanderWeele, Vanderbilt University, Nashville. USA

Larry Young, Emory University, Atlanta, USA

discussant: Kathryn Cunningham, University of Texas Medical Branch, Galverston, USA

 

Autism is an increasingly recognized, heritable behavioral disorder that, though first appearing by the age of three, typically imparts lifelong challenges to subjects, family members and caregivers. Beginning with the pioneering work of Leo Kanner in the 1940s, autism has been recognized to display a triad of symptoms - problems in language development, deficits in social interactions, and the presence of rigid, repetitive behaviors. Most recently, the designation “Autism Spectrum Disorder “, or ASD, has been introduced to recognize the variability of symptoms among individuals, and the prospect that underlyingfoundations account for shared deficits among subjects not meeting strict autism criteria. Although both common and rare gene variation supporting ASD risk have been identified, we remain ignorant of when, where and how these changes produce the key traits of ASD. Studies with animal models of rare, genetic disorders that bear ASD features suggest that knowledge of the neurobiological contributions of the impacted genes may lead to targeted therapies that can ameliorate or reverse ASD deficits, even when interventions are initiated in older subjects.

In this course, we explore the neurobiological underpinnings of autism, integrating prior and emerging findings that define the molecular, systems and cognitive attributes of ASD. We move from case studies that reveal key ASD traits and aspects of ASD heterogeneity, to epidemiological studies that provide estimates of ASD incidence, prevalence and heritability. We review the methodologies and tools applied by geneticists who seek clues to ASD heritability and risk and examine how findings may be organized into functional networks. We examine the normal patterns of brain development in the context of circuits that can contribute to distinct ASD features, and illustrate the paths by which peripheral and parental physiology can support or restrict the normal course of brain development. We discuss the potential for disrupted synaptic structure and function in relation to discoveries of rare ASD-associated variants in synaptic genes. We review findings of biochemical, structural and pathological changes in ASD subjects, with an eye to the use and limits of biomarkers. We study the synaptic and circuit level changes displayed by rare, heritable disorders with ASD features and discuss the relevance of these disorders for understanding the mechanisms underlying idiopathic ASD. We explore new opportunities to model ASD in animals, drawing on natural or introduced genetic variation, and reviewing methods that can detect deficits in communication, social and repetitive behaviors. We discuss the utility of structural and functional brain imaging technologies for testing cognitive models and circuit-level involvement in ASD deficits. Finally, we consider the path forward in linking preclinical and human neurocognitive studies to the development of novel therapeutics.

Internationally recognized U.S. and European scientists, whose ongoing research programs target ASD neurobiology from genetic, molecular, systems and cognitive perspectives, serve as faculty for the course. Students will leave the course with a broad appreciation of the major concepts, methods and models that organize current ASD research and have a better appreciation for the challenges and opportunities that lie ahead for improved ASD diagnosis and treatment.

We are grateful for the generous support of Roche (Basel, Switzerland).