Linking Neurogenetics and Functional Connectivity in Autism

The large neurobiological heterogeneity of autism spectrum disorder (ASD) and its genetic diversity have challenged our ability to identify how genetic risk translates into changes of brain structure and function and, finally, into behavioral symptoms. Various lines of evidence, stemming from genetics ( 1 Ruzzo E.K. Pérez-Cano L. Jung J.Y. Wang L.K. Kashef-Haghighi D. Hartl C. et al. Inherited and de novo genetic risk for autism impacts shared networks. Cell. 2019; 178: 850-866.e26 Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar , 2 Amaral D. Geschwind D. Dawson G. Autism Spectrum Disorders. Oxford University Press, New York2011 Crossref Google Scholar ), neuroimaging [reviewed in ( 3 Moreau C.A. Raznahan A. Bellec P. Chakravarty M. Thompson P.M. Jacquemont S. Dissecting autism and schizophrenia through neuroimaging genomics. Brain. 2021; 144: 1943-1957 Crossref PubMed Scopus (18) Google Scholar )], and behavioral phenotyping ( 4 Meng-Chuan L. Lombardo M.V. Baron-Cohen S. Autism. Lancet. 2014; 383: 896-910 Abstract Full Text Full Text PDF Scopus (1525) Google Scholar ), have highlighted the subtle and multifactorial mechanisms underlying the disease, which have resulted in limited success developing novel therapeutics. In the current issue of Biological Psychiatry, Rasero et al. ( 5 Rasero J. Jimenez-Marin A. Diez I. Toro R. Hasan M.T. Cortes J.M. The neurogenetics of functional connectivity alterations in autism: Insights from subtyping in 657 individuals. Biol Psychiatry. 2023; 94: 804-813 Abstract Full Text Full Text PDF Google Scholar ) attempt to characterize neural heterogeneity in ASD in a data-driven way by clustering large-scale resting-state functional brain connectivity profiles, searching for subtypes and links to phenotypic variation. Following previous lines of work linking neuroimaging findings to transcriptomic patterns ( 6 Richiardi J. Altmann A. Milazzo A.C. Chang C. Chakravarty M.M. Banaschewski T. et al. BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks. Science. 2015; 348: 1241-1244 Crossref PubMed Scopus (370) Google Scholar ), the study used high-resolution transcriptomic data from the Allen Human Brain Atlas ( 7 Hawrylycz M.J. Lein E.S. Guillozet-Bongaarts A.L. Shen E.H. Ng L. Miller J.A. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012; 489: 391-399 Crossref PubMed Scopus (1612) Google Scholar ) to identify genes enriched in brain regions with altered functional connectivity characteristic for each subtype. SEE CORRESPONDING ARTICLE ON PAGE 804 SEE CORRESPONDING ARTICLE ON PAGE 804 The Neurogenetics of Functional Connectivity Alterations in Autism: Insights From Subtyping in 657 IndividualsBiological PsychiatryVol. 94Issue 10PreviewThere is little consensus and controversial evidence on anatomical alterations in the brains of people with autism spectrum disorder (ASD), due in part to the large heterogeneity present in ASD, which in turn is a major drawback for developing therapies. One strategy to characterize this heterogeneity in ASD is to cluster large-scale functional brain connectivity profiles. Full-Text PDF Open Access