According to a new UCLA-led study that significantly improves scientists’ understanding of how autism spectrum disorder (ASD) develops at the molecular level, brain changes in autism are comprehensive throughout the cerebral cortex rather than just specific areas thought to affect social behaviour and language.
Author of the study and Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology, and Psychiatry at UCLA, Dr. Daniel Geschwind, said, “This work represents the culmination of more than ten years of work of many lab members, which was necessary to perform such a comprehensive analysis of the autism brain.” “Finally, molecular research is starting to paint a picture of the molecular makeup of the brains of people with an autism diagnosis. This gives us a molecular pathology that, like other brain disorders like Parkinson’s, Alzheimer’s, and stroke, offers a crucial starting point for understanding the mechanism of the sickness, which will guide and hasten the development of disease-altering therapeutics.”
Geschwind led the initial investigation into the molecular pathology of autism by concentrating on the temporal lobe and frontal lobe of the brain a little over ten years ago. The decision to focus on those regions was made because they are higher order association regions that are engaged in higher levels of cognition, particularly social cognition, which is impaired in ASD.
The study, which was just published in Nature, is an extensive attempt to define ASD at the molecular level. Autism and other psychiatric disorders lack a defining pathology, which makes it challenging to develop more effective treatments. In contrast, neurological disorders like Alzheimer’s disease and Parkinson’s disease have well-defined pathologies.
Whether they are upper critical association regions—those engaged in tasks like reasoning, language, social cognition, and mental flexibility—or primary sensory regions, the new study discovers brain-wide changes in almost all of the 11 cortical regions examined.
In the latest study, RNA from each of the four primary cortical lobes was sequenced in order to analyse gene expression in 11 different cortical areas. They contrasted samples of healthy brain tissue with brain tissue from 112 persons with ASD who had passed away.
The visual cortex and the parietal cortex, which process information including touch, pain, and temperature, revealed the most drop off in gene levels despite alterations in every analysed cortical region. According to the researchers, this may be a reflection of the sensory hypersensitivity that is typically noted in ASD patients. Researchers discovered compelling evidence that the genetic susceptibility to autism is enriched in a particular neural module with reduced expression throughout the brain,
suggesting that RNA modifications in the brain are more likely the cause of ASD than its effect.
In addition, researchers can utilise organoids to simulate the changes in order to better understand their causes. One of the following steps is to evaluate whether researchers can use computational methods to design medicines based on reversing gene expression changes that researchers found in ASD.