New! Sign up for our free email newsletter.
Science News
from research organizations

Brain changes in autism are far more sweeping than previously known, study finds

The study is the most comprehensive effort yet to study how autism affects the brain at the molecular level

Date:
November 2, 2022
Source:
University of California - Los Angeles Health Sciences
Summary:
Brain changes in autism are comprehensive throughout the cerebral cortex rather than just particular areas thought to affect social behavior and language, according to a new study that significantly refines scientists' understanding of how autism spectrum disorder (ASD) progresses at the molecular level.
Share:
FULL STORY

Brain changes in autism are comprehensive throughout the cerebral cortex rather than just particular areas thought to affect social behavior and language, according to a new UCLA-led study that significantly refines scientists' understanding of how autism spectrum disorder (ASD) progresses at the molecular level.

The study, published today in Nature, represents a comprehensive effort to characterize ASD at the molecular level. While neurological disorders like Alzheimer's disease or Parkinson's disease have well-defined pathologies, autism and other psychiatric disorders have had a lack of defining pathology, making it difficult to develop more effective treatments.

The new study finds brain-wide changes in virtually all of the 11 cortical regions analyzed, regardless of whether they are higher 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 of many lab members, which was necessary to perform such a comprehensive analysis of the autism brain," said study author Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at UCLA. "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."

Just over a decade ago, Geschwind led the first effort 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.

For the 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.

While each profiled cortical region showed changes, the largest drop off 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.Researchers 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.

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.

Other authors include Michael J. Gandal, Jillian R. Haney, Brie Wamsley, Chloe X. Yap, Sepideh Parhami, Prashant S. Emani, Nathan Chang, George T. Chen, Gil D. Hoftman, Diego de Alba, Gokul Ramaswami, Christopher L. Hartl, Arjun Bhattacharya, Chongyuan Luo, Ting Jin, Daifeng Wang, Riki Kawaguchi, Diana Quintero, Jing Ou, Ye Emily Wu, Neelroop N. Parikshak, Vivek Swarup, T. Grant Belgard, Mark Gerstein, and Bogdan Pasaniuc. The authors declared no competing interests.

This work was funded by grants to Geschwind (NIMHR01MH110927, U01MH115746, P50-MH106438 and R01MH109912, R01MH094714), Gandal (SFARI Bridge to Independence Award, NIMH R01-MH121521, NIMH R01-MH123922 and NICHD-P50-HD103557), and Haney (Achievement Rewards for College Scientists Foundation, Los Angeles Founder Chapter, UCLA Neuroscience Interdepartmental Program).


Story Source:

Materials provided by University of California - Los Angeles Health Sciences. Note: Content may be edited for style and length.


Journal Reference:

  1. Michael J. Gandal, Jillian R. Haney, Brie Wamsley, Chloe X. Yap, Sepideh Parhami, Prashant S. Emani, Nathan Chang, George T. Chen, Gil D. Hoftman, Diego de Alba, Gokul Ramaswami, Christopher L. Hartl, Arjun Bhattacharya, Chongyuan Luo, Ting Jin, Daifeng Wang, Riki Kawaguchi, Diana Quintero, Jing Ou, Ye Emily Wu, Neelroop N. Parikshak, Vivek Swarup, T. Grant Belgard, Mark Gerstein, Bogdan Pasaniuc, Daniel H. Geschwind. Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD. Nature, 2022; DOI: 10.1038/s41586-022-05377-7

Cite This Page:

University of California - Los Angeles Health Sciences. "Brain changes in autism are far more sweeping than previously known, study finds." ScienceDaily. ScienceDaily, 2 November 2022. <www.sciencedaily.com/releases/2022/11/221102123603.htm>.
University of California - Los Angeles Health Sciences. (2022, November 2). Brain changes in autism are far more sweeping than previously known, study finds. ScienceDaily. Retrieved October 31, 2024 from www.sciencedaily.com/releases/2022/11/221102123603.htm
University of California - Los Angeles Health Sciences. "Brain changes in autism are far more sweeping than previously known, study finds." ScienceDaily. www.sciencedaily.com/releases/2022/11/221102123603.htm (accessed October 31, 2024).

Explore More

from ScienceDaily

RELATED STORIES