A large study of postmortem brains reports detailed molecular changes in autism and how they relate to genetic susceptibility
By Azra Jaferi, Ph.D.
Introduction
Autism spectrum disorder (ASD) can affect people in different ways, from the types of symptoms experienced, how severe the symptoms are, and how much support people need in their daily lives. There are also many differences (called variants) in genes that increase the likelihood of developing ASD. Despite all of these differences in symptoms and genetics from one person to the next, researchers have found common alterations in the brains of people with ASD. Some of these common biological changes include an increased activity of genes related to the immune system; a decreased activity of genes involved in the communication between brain cells; and changes in the typical patterns of gene expression in the cortex, an area of the brain responsible for high-level cognitive abilities or thinking.1,2
Much of the evidence about changes in the brains of people with autism comes from research examining postmortem brain tissue in a bulk form, which contains a mixture of different types of cells. While analysis of bulk tissue has provided critical information about biological changes in the brains of people with ASD, studying brain tissue as a whole might miss important details about specific cell types. To address this, a recent study3 led by Daniel Geschwind at the University of California, Los Angeles looked at specific cell types in which molecular changes are occurring in postmortem brains and how they relate to genetic likelihood for an ASD diagnosis. This research is part of a larger project called PsychENCODE, which aims to learn more about brain-related disorders carried out by the National Institute of Mental Health consortium.
Methodology
Geschwind and his team analyzed gene expression at the level of individual cells in the brain. They isolated and identified genetic information from over 800,000 individual cells from postmortem brain tissue donated by 33 individuals with ASD and 30 without ASD (the largest analysis of this kind to date).
Findings and implications for autism
The study found that specific types of cells, called glial cells, may be affected in individuals with ASD. These cells, which normally support and protect neurons, seem to become more activated and in a proinflammatory state. The study also highlighted changes in certain types of neurons that connect the two hemispheres of the brain and between brain regions that are far apart, as well as in a group of interneurons, called somatostatin interneurons, that help keep the activity of other neurons balanced and regulated.
Overall, this postmortem brain study provides new insight into the molecular changes observed in the brains of people with ASD, the specific cell types in which these changes occur, and how they relate to genetic links to an ASD diagnosis. The findings ultimately move us closer to understanding the potential causes of ASD.