The latest research conducted by Michael Gandal, Ph.D., associate professor of psychiatry at Pennsylvania in Philadelphia, has found a distinct brain signature for autism.

The study conducted an extensive RNA-sequencing analysis of samples from the brains of 49 individuals with autism spectrum disorder (ASD) and 54 individuals without ASD. Results showed when examining the brain from anterior-to-posterior regions of the brain, gene expression differences were more pronounced in non-autistic, while in the brain of autistic individuals, these differences were more homogenous.

Professor Gandal elaborates on the study by saying there’s a “striking pattern” when examining gene expression differences from the front to the back of the cerebrum. Non-autistic have more pronounced gene-expression differences, while Autistic have more of the same genes dysregulated (muted).

He explains that the most pronounced differences were in sensory areas like the auditory and visual cortices, suggesting that this “brain signature” affects critical biological processes.

Gandal and his team further note that these dysregulation genes are mainly connected with neurons, synapses, oligodendrocytes, and microglia, thus affecting synaptic functions.

The study analyzed 11 cortical regions of the brain’s four lobes (frontal, parietal, temporal, and occipital), revealing a disrupted gene co-expression in BA 17 and BA-7. Brodmann area 17 is the area that handles visual information, while Brodmann area 7 connects visual and motor information. According to Gandal, this signature could offer a clue as to the origin of the changes.

Arnold Kriegstein, a neurology professor at the University of California, adds that most people  think of autism as “a disorder of the connection between neurons.” Still, this study suggests a clue to a surprising new role for gene expression. He says that “most people wouldn’t suspect the primary visual cortex to be driving autism.”

While the study provides new information as regards the role of genes, one of the study’s reviewers challenged the conclusion that the brain signature is obviously due to cell composition and not connected dysregulation. In other words, the Cells may have changed the composition of their membranes to adapt to different environmental conditions.

However, Gandal and his team debunked this hypothesis by sequenced RNAs from more than 250,000 individual cells. The cells were taken from six non-autism participants and six autism participants. Results showed that the number of astrocytes (specialized glial cells)  was surprisingly high in autistic participants, while excitatory neurons were lower.

According to Geschwind, a neurology professor, and psychiatrist at the University of California, this study is essential & provides the opportunity to ask new research questions on how these genetic changes occur and what other brain structures are involved.

Geschwind says that the dysregulated genes predominantly show up in brain areas that receive instructions from the thalamus, suggesting a potential route for gene regulation from outside brain structures. The thalamus is the hub of sensory information, and this study shows that it could be involved.

Kriegstein, a neurology professor, adds, “it’s worth exploring the possibility of gene expression dysregulation in other brain areas, such as the thalamus. The results could be surprising.”

It is too early to conclude the role of gene expression dysregulation in autism and related disorders. However, Gandal and his team’s findings provide important clues to understanding how genes are involved in autism, paving the way for further research into potential treatments or interventions.

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