Atypical patterns of brain gene expression appear to be shared by those across the autism spectrum
Genes abnormally expressed in brains affected by autism (red circles) cluster into networks that control similar brain functions.
As its name suggests, autism spectrum disorder (ASD) is known for its broad range, or spectrum, of outcomes—from profoundly disabled to highly but “differently” functional. Recent years have likewise revealed a diversity of genes that predispose to the development of ASD.
But this year, scientists discovered a remarkable consistency in the molecular changes occurring in the brains of those with ASD, across a range of autism subtypes. The study found two interconnected gene networks abnormally expressed in the brains of affected persons. The results suggest that diverse types of autism may share a similar biological basis.
Published in Nature, the study analyzed postmortem brain tissue donated to Autism Speaks Autism Tissue Program and was led by neurologist-geneticist Daniel Geschwind, M.D., Ph.D., of the University of California, Los Angeles, and Irina Voineagu, now at the Riken Brain Science Institute in Japan.
The team discovered that, within brains affected by autism, genes involved in cell function tended to be expressed at abnormally low levels, while genes associated with the generation of certain immune cells were expressed at higher than normal levels. Many of these genes are first turned on during embryonic development, they noted, suggesting that the abnormal development of brains affected by autism may begin very early.
In addition, the researchers looked closely at gene expression in the frontal cortex, the part of the brain that controls higher-level thinking, and in the temporal cortex, which controls sensory integration. In brains not affected by autism, the researchers found stark difference in gene expression between the two regions—as would be expected by their different functions. By contrast, these differences in frontal versus temporal lobe gene expression all but disappeared in those affected by autism. The results suggest a blurring of key differences during prenatal brain development. Such findings offer clues to both the causes of autism and guidance for developing medicines that might target autism’s disabling symptoms.
Voineagu I, Wang X, Johnston P, et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature. 2011 May 25;474(7351):380-4.