TY - JOUR
T1 - Differences in Intrinsic Gray Matter Connectivity and Their Genomic Underpinnings in Autism Spectrum Disorder
AU - the EU-AIMS LEAP group
AU - Leyhausen, Johanna
AU - Schäfer, Tim
AU - Gurr, Caroline
AU - Berg, Lisa M.
AU - Seelemeyer, Hanna
AU - Pretzsch, Charlotte M.
AU - Loth, Eva
AU - Oakley, Bethany
AU - Buitelaar, Jan K.
AU - Beckmann, Christian F.
AU - Floris, Dorothea L.
AU - Charman, Tony
AU - Bourgeron, Thomas
AU - Banaschewski, Tobias
AU - Jones, Emily J.H.
AU - Tillmann, Julian
AU - Chatham, Chris
AU - Ahmad, Jumana
AU - Ambrosino, Sara
AU - Auyeung, Bonnie
AU - Baron-Cohen, Simon
AU - Baumeister, Sarah
AU - Bölte, Sven
AU - Bours, Carsten
AU - Brammer, Michael
AU - Brandeis, Daniel
AU - Brogna, Claudia
AU - de Bruijn, Yvette
AU - Chakrabarti, Bhismadev
AU - Cornelissen, Ineke
AU - Crawley, Daisy
AU - Dell'Acqua, Flavio
AU - Dumas, Guillaume
AU - Durston, Sarah
AU - Ecker, Christine
AU - Faulkner, Jessica
AU - Frouin, Vincent
AU - Garcés, Pilar
AU - Goyard, David
AU - Ham, Lindsay
AU - Hayward, Hannah
AU - Hipp, Joerg
AU - Holt, Rosemary
AU - Johnson, Mark H.
AU - Kundu, Prantik
AU - Lai, Meng Chuan
AU - D'ardhuy, Xavier Liogier
AU - Lombardo, Michael V.
AU - Lythgoe, David J.
AU - Mandl, René
N1 - Publisher Copyright:
© 2023 Society of Biological Psychiatry
PY - 2024/1/15
Y1 - 2024/1/15
N2 - Background: Autism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs. Methods: Here, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group differences were assessed using a general linear model. A gene expression decoding analysis based on the Allen Human Brain Atlas was performed to link neuroanatomical differences to putative underpinnings. Results: Group differences in global and local wiring costs were predominantly observed in medial and lateral prefrontal brain regions, in inferior temporal regions, and at the left temporoparietal junction. The resulting neuroanatomical patterns were enriched for genes that had been previously implicated in the etiology of autism at genetic and transcriptomic levels. Conclusions: Based on intrinsic gray matter connectivity, the current study investigated the complex neuroanatomy of autism and linked between-group differences to putative genomic and/or molecular mechanisms to parse the heterogeneity of autism and provide targets for future subgrouping approaches.
AB - Background: Autism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs. Methods: Here, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group differences were assessed using a general linear model. A gene expression decoding analysis based on the Allen Human Brain Atlas was performed to link neuroanatomical differences to putative underpinnings. Results: Group differences in global and local wiring costs were predominantly observed in medial and lateral prefrontal brain regions, in inferior temporal regions, and at the left temporoparietal junction. The resulting neuroanatomical patterns were enriched for genes that had been previously implicated in the etiology of autism at genetic and transcriptomic levels. Conclusions: Based on intrinsic gray matter connectivity, the current study investigated the complex neuroanatomy of autism and linked between-group differences to putative genomic and/or molecular mechanisms to parse the heterogeneity of autism and provide targets for future subgrouping approaches.
KW - ASD
KW - Imaging genetics
KW - Intrinsic wiring costs
KW - MRI
KW - Neuroimaging
UR - http://www.scopus.com/inward/record.url?scp=85168350197&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2023.06.010
DO - 10.1016/j.biopsych.2023.06.010
M3 - Article
AN - SCOPUS:85168350197
SN - 0006-3223
VL - 95
SP - 175
EP - 186
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 2
ER -