GABAergic Dysfunction in Autism
Johns Hopkins University
Meixner Translational Postdoctoral Fellowship
Autism Spectrum Disorder (ASD) has a great impact on the lives of those with the disorder and the people around them. The underlying causes of ASD are not well understood and ASD symptoms vary widely in type and degree. The inhibitory brain chemical GABA is known to be linked to brain development, cognitive functioning, and the processing of sensory information (e.g. touch). Growing evidence links a dysfunction in this GABA system to aspects of autism, particularly impairments in sensory processing (e.g. hyper/hyposensitivity to touch). Recently, it has become possible to measure the amount of GABA in a particular brain area non-invasively using an MRI technique called magnetic resonance spectroscopy (MRS). In a 10 min MRI scan, researchers can obtain reliable measurements of GABA. The research team has recently shown that differences in GABA among healthy subjects can explain performance differences on sensory tasks. For example, GABA concentration in the area of the brain that controls touch and movement (sensorimotor cortex) correlates with touch discrimination. These findings have particular relevance for ASD, because an atypical response to touch is a common (and diagnostic) feature of ASD and one that can substantially impair behavior. In this project, the fellow aims to test whether this relationship between GABA and touch explains the abnormal touch sensitivity often seen in ASD. The fellow will use MRS to look at GABA in combination with touch processing paradigms, to investigate whether there is a measurable difference in the GABA system in children with ASD, and whether this is related to autism-associated differences in the processing of touch. The findings from GABA MRS and its association with autistic behavior will provide a foundation for investigating novel treatment therapies, specifically use of medications that affect the GABA system. This project translates the major finding (or focus) of the applicant’s PhD research to a new, clinical arena (ASD research) in which it has clear relevance. In addition to the fellow’s primary mentors, the fellow’s current expertise will be augmented by mentors from Johns Hopkins University (JHU) and Kennedy Krieger to provide a deeper understanding of ASD, including diagnosis, treatment and clinical autism research. Further educational benefit will come from attending courses at taught at JHU, weekly local seminars and international research conferences.