TY - JOUR
T1 - Decomposing the Brain in Autism
T2 - Linking Behavioral Domains to Neuroanatomical Variation and Genomic Underpinnings
AU - EU-AIMS LEAP group
AU - Seelemeyer, Hanna
AU - Gurr, Caroline
AU - Leyhausen, Johanna
AU - Berg, Lisa M.
AU - Pretzsch, Charlotte M.
AU - Schäfer, Tim
AU - Hermila, Bassem
AU - Freitag, Christine M.
AU - Loth, Eva
AU - Oakley, Bethany
AU - Mason, Luke
AU - Buitelaar, Jan K.
AU - Beckmann, Christian F.
AU - Floris, Dorothea L.
AU - Charman, Tony
AU - Banaschewski, Tobias
AU - Jones, Emily
AU - Bourgeron, Thomas
AU - Murphy, Declan
AU - Ecker, Christine
N1 - Publisher Copyright:
© 2024 Society of Biological Psychiatry
PY - 2025
Y1 - 2025
N2 - Background: Autism is accompanied by highly individualized patterns of neurodevelopmental differences in brain anatomy. This variability makes the neuroanatomy of autism inherently difficult to describe at the group level. Here, we examined interindividual neuroanatomical differences using a dimensional approach that decomposed the domains of social communication and interaction (SCI), restricted and repetitive behaviors (RRBs), and atypical sensory processing (ASP) within a neurodiverse study population. Moreover, we aimed to link the resulting neuroanatomical patterns to specific molecular underpinnings. Methods: Neurodevelopmental differences in cortical thickness (CT) and surface area (SA) were correlated with SCI, RRB, and ASP domain scores by regression of a general linear model in a large neurodiverse sample of 288 autistic individuals and 140 nonautistic individuals, ages 6 to 30 years, recruited within the European Autism Interventions Longitudinal European Autism Project (EU-AIMS LEAP). The domain-specific patterns of neuroanatomical variability were subsequently correlated with cortical gene expression profiles via the Allen Human Brain Atlas. Results: Across groups, behavioral variations in SCI, RRBs, and ASP were associated with interindividual differences in CT and SA in partially non-overlapping frontoparietal, temporal, and occipital networks. These domain-specific imaging patterns were enriched for genes that 1) are differentially expressed in autism, 2) mediate typical brain development, and 3) are associated with specific cortical cell types. Many of these genes were implicated in pathways governing synaptic structure and function. Conclusions: Our study corroborates the close relationship between neuroanatomical variation and interindividual differences in autism-related symptoms and traits within the general framework of neurodiversity and links domain-specific patterns of neuroanatomical differences to putative molecular underpinnings.
AB - Background: Autism is accompanied by highly individualized patterns of neurodevelopmental differences in brain anatomy. This variability makes the neuroanatomy of autism inherently difficult to describe at the group level. Here, we examined interindividual neuroanatomical differences using a dimensional approach that decomposed the domains of social communication and interaction (SCI), restricted and repetitive behaviors (RRBs), and atypical sensory processing (ASP) within a neurodiverse study population. Moreover, we aimed to link the resulting neuroanatomical patterns to specific molecular underpinnings. Methods: Neurodevelopmental differences in cortical thickness (CT) and surface area (SA) were correlated with SCI, RRB, and ASP domain scores by regression of a general linear model in a large neurodiverse sample of 288 autistic individuals and 140 nonautistic individuals, ages 6 to 30 years, recruited within the European Autism Interventions Longitudinal European Autism Project (EU-AIMS LEAP). The domain-specific patterns of neuroanatomical variability were subsequently correlated with cortical gene expression profiles via the Allen Human Brain Atlas. Results: Across groups, behavioral variations in SCI, RRBs, and ASP were associated with interindividual differences in CT and SA in partially non-overlapping frontoparietal, temporal, and occipital networks. These domain-specific imaging patterns were enriched for genes that 1) are differentially expressed in autism, 2) mediate typical brain development, and 3) are associated with specific cortical cell types. Many of these genes were implicated in pathways governing synaptic structure and function. Conclusions: Our study corroborates the close relationship between neuroanatomical variation and interindividual differences in autism-related symptoms and traits within the general framework of neurodiversity and links domain-specific patterns of neuroanatomical differences to putative molecular underpinnings.
KW - Autism spectrum disorder
KW - Autism symptoms
KW - Brain structure
KW - MRI
UR - http://www.scopus.com/inward/record.url?scp=105000267181&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2024.12.003
DO - 10.1016/j.bpsc.2024.12.003
M3 - Article
C2 - 39701384
AN - SCOPUS:105000267181
SN - 2451-9022
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
ER -