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Brain changes in autism more comprehensive than affecting specific areas: Study

09:37 AM Nov 04, 2022 | PTI |

Brain changes in autism are comprehensive throughout the cerebral cortex rather than specific areas thought to impact social behaviour and language, a new study has found.

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According to the study, it represents a comprehensive effort to characterise autism spectrum disorder (ASD) at the molecular level.

While neurological disorders like Alzheimer’s disease or Parkinson’s disease have well-defined pathologies or pathways, autism and other psychiatric disorders have had a lack of defining pathology, making it difficult to develop more effective treatments, it said.

The study, led by University of California, Los Angeles, finds brain-wide changes in virtually all of the 11 cortical regions analyzed, regardless of whether they are associated with higher functions such as reasoning, language, social cognition and mental flexibility or primary sensory regions.

The findings are published in Nature.

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“This work represents the culmination of more than a decade of work of many lab members, which was necessary to perform such a comprehensive analysis of the autistic brain,” said study author Daniel Geschwind.

“We now finally are beginning to get a picture of the state of the brain, at the molecular level, of the brain in individuals who had a diagnosis of autism.

“This provides us with a molecular pathology, which similar to other brain disorders such as Parkinson’s, Alzheimer’s and stroke, provides a key starting point for understanding the disorder’s mechanisms, which will inform and accelerate development of disease-altering therapies,” he said.

For this new study, researchers examined gene expression in 11 cortical regions by sequencing RNA from each of the four main cortical lobes. They compared brain tissue samples obtained after death from 112 people with ASD against healthy brain tissue, the study said.

While each profiled cortical region showed changes, the largest fall in gene levels were in the visual cortex and the parietal cortex, which processes information like touch, pain and temperature. The researchers said this may reflect the sensory hypersensitivity that is frequently reported in people with ASD, the study said.

Researchers also found strong evidence that the genetic risk for autism is enriched in a specific neuronal module that has lower expression across the brain, indicating that RNA changes in the brain are likely the cause of ASD rather than a result of the disorder.

Geschwind led the first effort, over a decade ago, to identify autism’s molecular pathology by focusing on two brain regions, the temporal lobe and the frontal lobe. Those regions were chosen because they are higher order association regions involved in higher cognition – especially social cognition, which is disrupted in ASD.

One of the next steps is to determine whether researchers can use computational approaches to develop therapies based on reversing gene expression changes the researchers found in ASD, Geschwind said, adding that researchers can use organoids to model the changes in order to better understand their mechanisms.

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