Scientists at Yale School of Medicine have identified significant molecular differences in the brains of individuals with autism compared to their neurotypical peers. This discovery, published in the American Journal of Psychiatry, sheds light on the neurobiological underpinnings of autism, a complex neurodevelopmental condition characterized by challenges in social interaction, restricted interests, and repetitive behaviors.
The study reveals that brains of autistic individuals exhibit a reduced presence of a specific type of glutamate receptor, known as metabotropic glutamate receptor 5 (mGlu5). Glutamate is the primary excitatory neurotransmitter in the brain, playing a crucial role in neuronal communication. The reduced availability of these receptors may correlate with various traits associated with autism.
According to James McPartland, PhD, Harris Professor of Child Psychiatry and Psychology at Yale and co-principal investigator of the study, “We have found this really important, never-before-understood difference in autism that is meaningful, has implications for intervention, and can help us understand autism in a more concrete way than we ever have before.”
The research involved a comparison of brain activity between 16 autistic adults and 16 neurotypical individuals. Utilizing both magnetic resonance imaging (MRI) and positron emission tomography (PET), the team aimed to uncover differences in brain structure and function. MRI scans provided anatomical insights, while PET scans enabled the researchers to visualize the molecular activity related to glutamate signaling.
David Matuskey, MD, associate professor of radiology and biomedical imaging at Yale and co-principal investigator, emphasized the importance of PET scans in mapping the glutamate system, stating, “PET scans can help us pinpoint a molecular map of what’s going on in this glutamate system.”
Findings indicated a lower overall availability of mGlu5 receptors in the brains of the autistic participants, supporting the hypothesis that an imbalance between excitatory and inhibitory signaling may contribute to the diverse characteristics observed in autism. Additionally, fifteen of the autistic participants underwent an electroencephalogram (EEG) to measure electrical brain activity. The EEG results aligned with the PET findings, further suggesting a relationship between mGlu5 receptor levels and electrical brain activity.
The implications of this research are profound. While PET scans are valuable, they are costly and involve radiation exposure. EEG could serve as a more accessible method to investigate excitatory function in the brain, as noted by Adam Naples, PhD, assistant professor in the Child Study Center at Yale and the study’s first author. “EEG isn’t going to completely replace PET scans, but it might help us understand how these glutamate receptors might be contributing to the ongoing brain activity in a person,” he explained.
Understanding the molecular basis of autism could eventually lead to enhanced diagnostic tools and support strategies. Currently, autism is diagnosed primarily through behavioral observations, as the molecular mechanisms remain largely uncharted. McPartland highlighted the significance of their findings, stating, “Now, we’ve found something that is meaningful, measurable, and different in the autistic brain.”
At present, there are no medications that specifically address the challenges faced by many individuals on the autism spectrum. The study’s findings might inform the development of targeted therapies aimed at the mGlu5 receptor, potentially benefiting those whose symptoms significantly impact their quality of life.
The research focused exclusively on autistic adults, leaving open questions about whether the lower receptor availability is a cause of autism or a consequence of living with the condition for extended periods. Past studies utilizing PET scans have typically involved adults due to safety concerns regarding radiation exposure. However, Matuskey, along with co-investigator Richard Carson, PhD, have developed advanced techniques that promise to minimize radiation exposure in future studies.
Looking ahead, the research team plans to explore these new technologies in children and adolescents, aiming to build a comprehensive developmental narrative. “We want to start creating a developmental story and start understanding whether the things that we’re seeing are the root of autism or a neurological consequence of having had autism your whole life,” McPartland remarked.
All autistic participants in this study had average or above-average cognitive abilities, and the research team is also working on methodologies that may include individuals with intellectual disabilities in future investigations. As scientists delve deeper into the molecular aspects of autism, new pathways may emerge for understanding and supporting individuals on the spectrum.
