Exploring the Link Between Brain Organization and Genetic Markers for Autism and Schizophrenia
The intricate structure of the human brain is a marvel of nature, developed through the elaborate orchestration of gene expression. Discovering how the orderly arrangement of brain regions connects to genes implicated in mental health disorders like autism and schizophrenia may illuminate the underlying biological mechanisms of these conditions. A groundbreaking study spearheaded by researchers from the University of Cambridge, alongside global partners, provides new insights into this complex relationship.
Published in Nature Neuroscience, their research correlates gene expression in neurotypical brains with the imaging, transcriptomics, and genetics associated with autism spectrum disorder and schizophrenia. The study reveals three specific spatial patterns of cortical gene expression, each linked to either autism or schizophrenia in distinct ways.
Richard Dear, a co-author of the study, shared with Medical Xpress, “Previous research identified a universal spatial pattern of gene expression within human brains. This pattern reflects the neural connectivity hierarchy. However, our hypothesis posited the existence of additional patterns underpinning how genes are expressed across the brain’s landscape.”
The team’s primary aim was to unearth new spatial gene expression patterns to understand the transcriptional programs— the biological processes guiding brain development in both its healthy form and in disease states.
Dear mentioned, “A significant hurdle was the scarcity of available data. The Allen Human Brain Atlas remains the sole source of high-resolution gene expression data across the brain, compiled from merely six healthy individuals. It was imperative to discern patterns within this data that represent universal transcriptional programs.”
To validate their findings, the research group employed various computational analyses, including a robustness test and validation against three independent data types. They sought associations with known data on brain organization, development, gene expression, and genetic variants linked to both healthy and disordered brain function.
“The consistency of our findings across these analyses was remarkable,” Dear remarked. “We discovered that the second gene expression pattern is associated with cognitive metabolism and autism, whereas the third corresponds to brain plasticity during adolescence and schizophrenia. Intriguingly, both patterns were identified solely in neurotypical brains.”
This pioneering research marks the first instance of connecting neurotypical brain gene expression patterns to autism and schizophrenia using prior data from case-control neuroimaging, differential gene expression studies, and genome-wide association studies. The implications are profound, suggesting that seemingly disparate data can be unified under common transcriptional programs driving healthy brain development.
Looking ahead, Dear and his team plan to delve deeper into the biology of these patterns, leveraging cutting-edge single-nucleus RNA sequencing data. “We aim to pinpoint the critical genes and transcription factors that direct the expression of these patterns early in development and across different cell types,” Dear stated. The team also hopes that their findings and the analytical tools developed through this study will serve as valuable resources for scientists investigating the genetic foundations of brain spatial organization.
As the science community continues to unravel the genetic intricacies of the human brain, studies like these offer promising pathways to understanding and eventually treating complex mental health disorders.
