Uno studio meta-analitico della relazione tra le anomalie neuroanatomiche e l’espressione genica nello spettro dell’autismo

Background: Autism spectrum disorder (ASD) is a set of developmental conditions with widespread neuroanatomical abnormalities and a strong genetic basis. Although neuroimaging studies have indicated anatomical changes in grey matter (GM) morphometry, their associations with gene expression remain elusive. Methods: Here, we aim to understand how gene expression correlates with neuroanatomical atypicalities in ASD and how this is related with functional large-scale networks. To do so, we performed a coordinate-based meta-analysis to determine the common GM variation pattern in the autistic brain. From the Allen Human Brain Atlas, we selected eight genes from the SHANK, NRXN, NLGN family and MECP2, which have been implicated with ASD, particularly in regards to altered synaptic transmission and plasticity. The gene expression maps for each gene were built. We then assessed the correlation between the gene expression maps and the GM alteration maps. Lastly, we evaluated how the correlation varied across selected resting state networks, by averaging the correlation coefficient of the voxels belonging to each network. Results:We found that gene expression of most genes correlated with GM alteration (both increase and decrease) in regions located in the default mode network. Decreased GM was also correlated with gene expression of some ASD genes in areas associated with the dorsal attention and cerebellar network. Lastly, single genes were found to be significantly correlated with increased GM in areas located in the somatomotor, limbic and ganglia/thalamus networks. Conclusions: This approach allowed us to combine the well beaten path of genetic and brain imaging in a novel way, to specifically investigate the relation between gene expression and brain with structural damage, and individuate genes of interest for further investigation in specific functional networks.