Understanding the Autistic Brain is the most comprehensive molecular study published today in Nature to date

▎WuXi AppTec content team editor  

Autism, also known as autism spectrum disorder (ASD) in medicine, is a complex brain disorder that has gradually attracted public attention
in recent years.
The China Autism Development Report estimates that there may be more than 10 million autistic people in China, and about 1 in 68 children have autism
.
Children with autism may have communication difficulties and language expression difficulties as early as infancy, and symptoms continue into adolescence and adulthood
.

Image source: 123RF

Compared with some other neurological diseases, such as Alzheimer's disease and Parkinson's disease, which we are more familiar with, autism has always lacked clear pathological features, so it is more difficult
to develop effective treatments.

After more than a decade of concerted efforts, a paper published today in the top academic journal Nature demonstrates scientists' most comprehensive understanding
of how autism affects the brain at the molecular level to date.

From the results of this study's analysis, brain changes in autism involve the entire cerebral cortex, not just specific brain regions
previously known to affect social behavior and language.

Leading the study is Dr.
Daniel Geschwind, a professor of neurology and psychiatry at UCLA, whose team applied systems biology approaches to neurological and psychiatric disorders, with one focus on identifying the genetic causes and molecular pathology of autism
.

Initially, the team focused on the frontal and temporal lobes of the brain, as these two regions are highly involved in the brain's higher cognitive functions, especially social cognition, which is one of
the core barriers in people with autism.

In the new study, the scientists expanded their examination by RNA sequencing all four functional areas of the cerebral cortex — the frontal, temporal, occipital and parietal lobes — and examining the cells' gene expression
in 11 regions.
In total, they analyzed samples of brain tissue donated after death from 112 autistic patients and compared
them with healthy brain tissue.

The analysis results show that the impact of autism on the brain is a brain-wide change, and almost all of the 11 cortical regions analyzed can see the difference between autistic patients and healthy controls, that is, including higher-level association areas, such as areas involved in reasoning, language, social cognition and other functions, as well as primary sensory areas
.

The researchers noticed that the regions with the greatest declines in gene levels were in the visual cortex and parietal cortex, which processes information
such as pain, touch, and temperature.
The researchers point out that autistic people often have "sensory hypersensitivity", such as ordinary sounds that sound extremely harsh to them, and touch and hug are unbearable for them, and this difference in gene expression may reflect this phenomenon
.

Research evidence shows that a specific set of neural networks in the entire brain of autistic people shows lower gene expression in the whole brain, and these changes in gene expression are more likely to be the cause than effect of
autism.
The research team says the next step is to develop therapies based on reversing these changes in gene expression, using techniques such as organoids that mimic human brain development to better understand the mechanisms
of autism.

Professor Geschwind concludes: "We are now finally beginning to understand the state of the brain of people diagnosed with autism at the molecular level
.
This provides us with molecular pathology, just as understanding brain diseases such as Parkinson's disease, Alzheimer's disease, stroke, etc.
, provides a key starting point for understanding the mechanisms of the disease, which will accelerate the development of
therapies.
”