Brain gene activity patterns split autism-risk mutations into two groups

Researchers identified two opposing patterns of brain gene activity across mice carrying different autism-risk mutations, grouping over 1,000 transcriptomes into shared molecular states. This framework could aid drug comparisons, with findings published in Science. Analyzing 17 genetically engineered mouse lines, the team found Group 1 showed reduced synaptic communication gene expression and increased chromatin regulation, while Group 2 displayed the opposite. Grouping varied by sex, developmental stage, and brain region, with drug responses to fluoxetine and lithium differing between groups. Examining human prefrontal cortex data from 40 autistic individuals revealed two similar subgroups, though immune-related changes were more prominent. Researchers caution the study establishes no clinical autism types, drug efficacy, or predictive value for symptoms, emphasizing preliminary findings requiring further behavioral and circuit studies.