Autism risk genes converge into two opposing brain states with distinct drug responses

Researchers have discovered that over 1,200 autism risk genes converge into two opposing molecular states in the brain, which respond differently to experimental drugs, according to a study analyzing more than 1,000 mouse brain transcriptomes across 17 genetic lines. The two groups show inverse patterns of synaptic and gene-regulatory activity: Group 1 exhibits decreased synaptic communication genes with elevated chromatin and RNA processing activity, while Group 2 shows the opposite balance. Classification is not strictly genetic, as males and females with identical mutations fell into opposing groups in 7 of 17 strains, with patterns shifting across development and brain regions. Drug responses differed by group, with Group 1 showing more consistent normalization toward control gene expression after fluoxetine or lithium exposure than Group 2. Human prefrontal cortex data from 40 autistic individuals revealed similar opposing subgroups, though researchers caution findings are exploratory and cannot yet guide clinical diagnosis or treatment selection.