Abstract Details

Title Investigating Metabotropic Glutamate Receptor 5 (mGluR5) in Autism Spectrum Disorder with [18F]FPEB PET Imaging

Topic Child Neurology and Developmental Neurology

Presentation(s) S8 - State-of-the-art Diagnostics in Child Neurology (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background The neural basis of autism spectrum disorder (ASD) is poorly understood at the molecular level. Evidence from animal models, genetics, post-mortem studies, and single-gene disorders suggests a possible involvement of metabotropic glutamate receptor 5 (mGluR5).

Objective We aim to quantify mGluR5 availability in autistic adults using the specific binding PET tracer [¹⁸F]FPEB.

Design/Methods

Sixteen autistic individuals (mean age ±SD: 25.93± 4.69, 11 males, 5 females), and sixteen demographically matched neurotypical (NT) individuals (mean age ±SD:28.43 ± 3.31, 11 males, 5 females) were scanned using a positron emission tomography (PET) high-resolution research tomograph (HRRT). Volume of distribution (V_T: ratio of activity in tissue relative to blood) was the primary outcome measure and computed with equilibrium analysis using a venous input function. Brain regions were delineated with a defined anatomic template applied to subjects' structural MR scans. Partial volume corrections were applied to control for possible volumetric differences. T-tests were calculated for between-group differences, and p-values were uncorrected for multiple comparisons, given the exploratory nature of this work.

Results

We observed significantly lower mGluR5 availability in all regions, that varied from -16% to -23% in ASD compared to NT. This was lowest in the left frontal pole ( -23%, p=0.003) and left cingulate (-23%, p=0.003) and included important areas such as the frontal lobe (-19%, p=0.01), temporal lobe (-19%, p=0.01), cerebellum (-19%, p<0.01) and fusiform gyrus (-18%, p=0.02).

Conclusions

This in vivo investigation with mGluR5 PET in people with ASD is the largest sample to date (to our knowledge) and found robust preliminary evidence of lower mGluR5 availability compared to NT.

Authors/Disclosures
Faranak Ebrahimian Saadabad PRESENTER	Mr. Ebrahimian Saadabad has nothing to disclose.
Yanghong Yang, MD	Ms. Yang has nothing to disclose.
Paul Gravel (Yale University)	No disclosure on file
Adam Naples	No disclosure on file
Kristen Torres	No disclosure on file
Nabeel Nabulsi	No disclosure on file
Jim Ropchan (Yale University)	No disclosure on file
Yiyun Huang	No disclosure on file
Ansel Hillmer	No disclosure on file
Irina Esterlis (Yale Translational Brain Imaging Program)	No disclosure on file
Richard E Carson	No disclosure on file
James McPartland (Yale Child Study Center)	No disclosure on file
David Matuskey, MD (Yale University)	Dr. Matuskey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Eleisver. The institution of Dr. Matuskey has received research support from Abbvie.