Spatial transcriptomics implicates the thalamus and cortex in autism and schizophrenia

Summary

This study, published in bioRxiv, looks at where autism and schizophrenia risk genes are most active in the mouse brain. The authors used spatial transcriptomics to compare many brain regions and found that autism-linked genes were most enriched in the thalamus, followed by the cortex. Schizophrenia-linked genes were also enriched in the thalamus, as well as the hippocampus and cortex.

The paper suggests that the thalamus may play a major part in both autism and schizophrenia, while the cortex and hippocampus may also be involved. It shows that these brain disorders may share some patterns, but also have some differences, which could help scientists understand the circuits involved in each condition.

Keywords: spatial transcriptomics, autism, schizophrenia, thalamus, cortex, hippocampus, mouse brain, gene enrichment, neuropsychiatric disorders, bioRxiv preprint.

Abstract

The past decade has seen tremendous progress in the identification of genes associated with complex neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. Expression patterns of these genes in single cell data strongly implicate excitatory and inhibitory neurons; however, there are limited data on the brain regions involved - a critical question for neurobiology. Spatial transcriptomics provide an opportunity to perform systematic multiregional analyses to provide insights into this question. Here, we have generated a spatial transcriptomics dataset encompassing the diverse anatomical territories of the adult mouse brain sagittal midsection. We compare neuropsychiatric gene enrichment by applying Gene Fraction Enrichment Score (GFES), a novel statistic method that controls for differing neuronal proportions across regions. ASD-associated genes identified by exome sequencing were most enriched in the thalamus followed by the cortex. Schizophrenia genes from genome-wide association studies were also enriched in the thalamus, along with the hippocampus and cortex. These findings add to the evidence that the thalamus plays a major role in neuropsychiatric disorders whilst supporting roles for the cortex and hippocampus. The results highlight shared and distinct patterns for pleiotropic brain disorders that could elucidate common underlying mechanisms and circuitry.