The GABAergic system has been found to be important in the pathophysiology of autism spectrum disorder(ASD), as evidenced by postmortem studies and animal models of ASD. The overall objective of thisapplication, which is a critical step toward attainment of my long-term goal, is to use a cutting-edgemethodology in assessing the GABAergic system in living human beings with ASD. We hypothesize that theGABAergic tone is lower in the thalamocortical network in the brains of individuals with ASD, compared toneurotypical controls. We further postulate that GABAA receptor densities and GABA levels in the DLPFC (orthalamus) will have an interactive effect on social-communicative abilities. The Specific Aims of this proposalare to: (1) characterize the distribution of GABAA receptors in adults with ASD; (2) determine the abnormalitiesin GABA levels in thalamocortical networks in adults with ASD; and (3) examine the independent andinteractive effects of GABAA receptor densities and GABA levels in the thalamus and DLPFC, on socio-communicative abilities.This 4-year program will involve training in specific neuroimaging methodologies, as well as general researchand ethics. Imaging methods used in this proposal will be positron emission tomography (PET), magneticresonance spectroscopy (MRS), and structural magnetic resonance imaging (sMRI). Antonio Hardan, M.D.(Director of Autism & Developmental Disabilities Clinic, Department of Psychiatry & Behavioral Sciences,Stanford University) and Greg Zaharchuk, M.D., Ph.D. (Associate Professor, Department of Radiology,Stanford University) will co-mentor the principal investigator's scientific development. Both Dr. Hardan and Dr.Zaharchuk have substantial experience in various areas of neuroimaging and in the application of relatedresearch methods, as well as experience training postdoctoral fellows and NIH grant recipients. The proposalis also supported by a rich diversity of collaborators and consultants to provide education and guidance invarious aspects of research (PET in individuals with ASD, MRS, and biostatistics). The principal investigatorhas completed residency training in Psychiatry, fellowship training in Child & Adolescent Psychiatry, and aPost-doctoral research fellowship at Stanford University School of Medicine. He also holds advanced degreesin Chemical Engineering, and has industry experience in pharmaceutical discovery and development.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
