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Abstract Details

Glutamatergic Dysfunction in Autism Spectrum Disorder
Child Neurology and Developmental Neurology
P1 - Poster Session 1 (8:00 AM-9:00 AM)
8-001
Based on animal and autopsy studies we hypothesized that metabotropic glutamate receptor subtype 5 (mGluR5) is increased in the brains of people with ASD.
To identify abnormalities in glutamatergic neurotransmission in autism spectrum disorder (ASD)
Positron emission tomography (PET) was performed on participants of both sexes with idiopathic autism spectrum disorder (IASD) (N=7, age 19.71 + 2.06) and typical development (TD) (N=19, age 34.89 + 14.57) and men with fragile X syndrome (FXS) (N=10, age 29.7 + 10.39) after the intravenous bolus injection of 185 MBq (5 mCi) 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB). [18F]FPEB uptake was represented as nondisplaceable binding potentials (BPND) in cortical [occipital cortex (Oc), parietal cortex (Pc), posterior cingulate cortex (pCg), and temporal cortex (Tc)] and subcortical regions [caudate nucleus (CN), putamen (Pu), and thalamus (Th)].
Box and dot plots of descriptive BPND statistics demonstrated group differences across the regions. To confirm the effects of group status (IASD versus TD versus FXS), analysis of variance (ANOVA) was performed with main factors (group and region) and covariates (age and sex). To confirm the significant effect of group on mGluR5 uptake demonstrated by ANOVA, Tukey's Honest Standard Differences was performed for pairwise comparisons. In contrast to participants with TD, mGluR5 expressions was increased in the cortical regions of participants with IASD and reduced in all regions of men with FXS.

mGluR5 expression was reduced in all FXS brain regions in contrast to IASD and TD. In men with FXS reduced mGluR5 expression in (A) cortical regions may suggest the pathophysiology for the intellectual disability and (B) limbic regions may suggest the pathophysiology for the neurobehavioral symptoms. 

mGluR5 expression was increased in cortical regions of the participants with IASD in contrast to those with TD and FXS.

These findings support the hypothesis that mGluR5 expression plays a role in the pathogenesis of IASD.

Authors/Disclosures
James R. Brasic, MD (Johns Hopkins University)
PRESENTER
Dr. Brasic has received personal compensation for serving as an employee of Medsurvy. Dr. Brasic has received personal compensation for serving as an employee of Webscape. Dr. Brasic has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Society of Nuclear Medicine and Molecular Imaging. Dr. Brasic has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multidisciplinary Digital Publishing Institute. Dr. Brasic has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Gerson Lehman Group.
Ayon Nandi (JHU) No disclosure on file
David S. Russell, MD, PhD (Invicro) Dr. Russell has received personal compensation for serving as an employee of Invicro. Dr. Russell has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurocrine. The institution of Dr. Russell has received research support from Biogen. The institution of Dr. Russell has received research support from Roche. The institution of Dr. Russell has received research support from Voyager. The institution of Dr. Russell has received research support from Eisai. The institution of Dr. Russell has received research support from Neuraly. The institution of Dr. Russell has received research support from Michael J. Fox Foundation. The institution of Dr. Russell has received research support from National Institutes for Health. The institution of Dr. Russell has received research support from Eli Lilly. The institution of Dr. Russell has received research support from Aprinoia.
Danna L. Jennings, MD (Denali Therapeutics) Dr. Jennings has received personal compensation for serving as an employee of Denali Therapeutics . Dr. Jennings has received stock or an ownership interest from Denali Therapeutics.
Olivier Barret (MIRCEN) No disclosure on file
Keith Slifer (Kennedy Krieger Institute) No disclosure on file
Thomas Sedlak (Johns Hopkins School of Medicine) No disclosure on file
John P. Seibyl, MD Dr. Seibyl has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Invicro. Dr. Seibyl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Seibyl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Life Molecular Imaging. Dr. Seibyl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Seibyl has received stock or an ownership interest from Invicro.
Elizabeth M. Berry-Kravis, MD, PhD (Rush University Medical Center) The institution of Dr. Berry-Kravis has received research support from NIH. The institution of Dr. Berry-Kravis has received research support from Ionis. The institution of Dr. Berry-Kravis has received research support from Zynerba. The institution of Dr. Berry-Kravis has received research support from Roche. The institution of Dr. Berry-Kravis has received research support from CDC. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation. The institution of Dr. Berry-Kravis has received research support from GeneTx. The institution of Dr. Berry-Kravis has received research support from Angelman Syndrome Foundation. The institution of Dr. Berry-Kravis has received research support from Acadia. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Anavex. The institution of Dr. Berry-Kravis has received research support from Rett Syndrome Research Trust. The institution of Dr. Berry-Kravis has received research support from Ultragenyx. The institution of Dr. Berry-Kravis has received research support from Mallinckrodt. The institution of Dr. Berry-Kravis has received research support from Together Strong Foundation. The institution of Dr. Berry-Kravis has received research support from Orphazyme. The institution of Dr. Berry-Kravis has received research support from Taysha. The institution of Dr. Berry-Kravis has received research support from Erydel. The institution of Dr. Berry-Kravis has received research support from Tetra. The institution of Dr. Berry-Kravis has received research support from Neuren. The institution of Dr. Berry-Kravis has received research support from FRAXA Research Foundation.
Dean Wong (Washington University in St Louis) No disclosure on file
Dejan Budimirovic No disclosure on file