Autism Spectrum Disorders

Abstract

Autism spectrum disorders was chosen as the topic for the 14th Neurobiology of Disease in Children Symposium, held on October 22-23, 2014, in Columbus, Ohio. Program codirectors Drs Stewart Mostofsky, Manny DiCicco-Bloom, and Deborah Hirtz prepared an engaging agenda that included individual presentations as well as a panel discussion from leaders working to advance the autism field. The symposium covered a variety of topics, such as clinical features, recent advances in understanding the pathogenesis of autism spectrum disorder, and new investigations of characteristic symptoms and behaviors categorized under the broad ‘‘spectrum’’ of autism. This was followed by a session on controversial topics and unanswered questions. The symposium concluded with a panel discussion led by scientific leaders in the field of autism spectrum disorders. Dr Sarah Spence opened the symposium with an introduction to autism, including changes to and advances in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Dr Spence explained how the DSM-5 criteria may provide clinicians with better diagnostic tools to properly diagnose certain symptoms, behaviors, and disabilities associated with autism spectrum disorder. Dr Craig Newschaffer then discussed the epidemiology of the disorder, addressing its rising prevalence in addition to genetic and environmental risk factors. Dr Lonnie Zwaigenbaum’s discussion stressed the importance of identifying early behavioral and neurological characteristics of autism spectrum disorder. In addition, he focused on the significance of early diagnosis and recent advances in early intervention. To conclude the first session, Dr Roberto Tuchman discussed the relationship between autism spectrum disorder and epilepsy, concentrating on the impact and shared mechanisms of both disorders. The next session of the symposium focused on recent progress in understanding the molecular mechanisms underlying different types of autism spectrum disorder. Dr Jonathan Sebat discussed the genetics of autism, summarizing studies of rare genetic variation, copy number variants, and exome sequencing, and new discoveries from comprehensive analysis of de novo mutations in autism. Dr Sebat described his work to identify copy number variation in the human genome as an important contributor to human disease. He also emphasized the genetic and hereditary factors contributing to various types of autism. Recently, Dr Sebat and his colleagues attempted to sequence the entire human genome in an effort to characterize patterns of mutation in both coding and noncoding regions of the genome. Dr Tim Roberts addressed the significance of biomarkers in autism, which can be used for diagnostic and prognostic purposes, in order to understand experimental models and to monitor response to therapy. Dr Roberts reviewed the application of magnetoencephalography for children with epilepsy or autism, discussing event-related potentials-type responses in auditory sensation and gamma-band activity. Dr Roberts also discussed his study of the motor cortex and concluded that g-aminobutyric (GABA) concentration predicted gamma band oscillation, in addition to GABA level variations observed in children with autism. To conclude the second session, Dr Cyndi Schumann focused on the current understanding of neuropathology and neurobiology of autism. Dr Schumann emphasized the importance of having brain tissue for autism research in order to make progress in the field. The third session of the symposium focused on translational and therapeutic targets in autism research. Dr Mustafa Sahin reviewed current translational work involving mice and human models with tuberous sclerosis complex. It is reported that about half of the patients who have tuberous sclerosis also might be affected by autism spectrum disorder. Therefore, his discussion was focused on the relationship between the mammalian target of rapamycin pathway and tuberous sclerosis complex, to test the role of tuberous sclerosis complex in autism. He also discussed studies in which the loss of 1 or both TSC1 and TSC2 genes resulted in disease. Dr Sahin and his colleagues conducted a study that focused on the non-tuber pathology of the brain in mice with tuberous sclerosis complex. His team demonstrated that miswiring the neural connectivity within the central nervous system had contributed to the pathogenesis of tuberous sclerosis. Last, Dr Sahin addressed the circuitry and localization of brain lesions and how these lesions might contribute to clinical abnormalities observed in patients.