Imaging Metabotropic Glutamate Receptor 5 and Excitatory Neural Activity in Autism

Area of Science:

• Neuroscience
• Molecular Psychiatry
• Neuroimaging

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social, communication, and sensory differences.
• Altered excitatory neurotransmission is implicated in ASD, but the underlying molecular mechanisms remain unclear.
• Metabotropic glutamate receptor 5 (mGlu5) plays a crucial role in modulating glutamatergic signaling.

Purpose of the Study:

• To investigate brain-wide metabotropic glutamate receptor 5 (mGlu5) availability in autistic adults.
• To explore the relationship between mGlu5 availability and excitatory activity measured by electroencephalography (EEG).
• To identify potential molecular mechanisms contributing to the heterogeneity of autism spectrum disorder.

Main Methods:

• Positron emission tomography (PET) with the tracer [18F]FPEB was used to measure mGlu5 availability (volume of distribution, VT) in 16 autistic and 16 neurotypical adults.
• Partial volume correction and equilibrium analysis with a venous input function were applied to PET data.
• Correlations between mGlu5 availability and the slope of the EEG power spectrum (an index of excitatory-inhibitory balance) were analyzed within the autistic group.

Main Results:

• Autistic adults exhibited significantly lower mGlu5 availability (~15%) across multiple brain regions compared to neurotypical controls, particularly in the cerebral cortex.
• Within the autistic group, lower mGlu5 availability was significantly correlated with a shallower EEG power spectrum slope, indicating altered excitatory-inhibitory balance.
• These findings suggest a widespread reduction in mGlu5 availability associated with altered excitatory neurotransmission in autism.

Conclusions:

• This study reveals pervasive lower mGlu5 availability in the brains of autistic adults.
• The findings link reduced mGlu5 availability to altered excitatory neurotransmission, potentially serving as a molecular mechanism underlying ASD.
• Lower mGlu5 availability may help stratify the heterogeneous presentation of autism spectrum disorder.