Brain changes in autism are far more comprehensive than previously known: study

The study, published today in the journal Nature, represents a comprehensive attempt to characterize ASD at the molecular level. While neurological disorders such as Alzheimer’s disease or Parkinson’s disease have well-defined pathologies, autism and other psychiatric disorders lack a defined pathology, which makes it difficult to develop more effective treatments.

The new study finds brain-wide changes in nearly all 11 cortical regions analyzed, whether they are more critical association regions — those involved in functions such as reasoning, language, social cognition and mental flexibility — or primary sensory regions .

“This work represents the culmination of more than a decade of work by many members of the lab, which was necessary to perform such a comprehensive analysis of the autistic brain,” said study author Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Sciences. Genetics, Neurology and Psychiatry at UCLA. “We are now finally starting to get a picture of the state of the brain, at the molecular level, of the brain in individuals who have been diagnosed with autism. This gives us the molecular pathology, which is similar to other brain disorders such as Parkinson’s, Alzheimer’s and stroke, provides a key starting point for understanding the mechanisms of the disorder, which will inform and accelerate the development of disease-modifying therapies.”

Just over a decade ago, Geschwind led the first effort to identify the molecular pathology of autism by focusing on two brain regions, the temporal lobe and the frontal lobe. These regions were chosen because they are higher-order regions involved in higher cognition — especially social cognition, which is impaired in ASD.

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

While every cortical region profiled showed changes, the biggest declines in gene levels were in the visual cortex and the parietal cortex, which processes information such as touch, pain and temperature. The researchers said this may reflect the sensory hypersensitivity that often occurs in people with ASD. The researchers found strong evidence that genetic risk for autism is enriched in a specific neuronal module that has lower expression in the brain, indicating RNA changes in the brain. they are likely the cause of ASD rather than the result of the disorder.

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

This story was published from the agency’s feed without changes to the text.