TY - JOUR
T1 - Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models
AU - Zabihi, Mariam
AU - Oldehinkel, Marianne
AU - Wolfers, Thomas
AU - Frouin, Vincent
AU - Goyard, David
AU - Loth, Eva
AU - Charman, Tony
AU - Tillmann, Julian
AU - Banaschewski, Tobias
AU - Dumas, Guillaume
AU - Holt, Rosemary
AU - Baron-Cohen, Simon
AU - Durston, Sarah
AU - Bölte, Sven
AU - Ecker, Christine
AU - Murphy, Declan
AU - Buitelaar, Jan K.
AU - Beckmann, Christian F.
AU - Marquand, Andre F.
PY - 2019/6
Y1 - 2019/6
N2 - Background: The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous. Methods: Here, we used an innovative normative modeling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertexwise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this, we employed a heterogeneous cross-sectional sample of 206 typically developing individuals (127 males) and 321 individuals with ASD (232 males) (6–31 years of age). Results: We found few case-control differences, but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing. Conclusions: Our results 1) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and 2) show that by focusing on common effects (i.e., the “average ASD participant”), the case-control approach disguises considerable interindividual variation crucial for precision medicine.
AB - Background: The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous. Methods: Here, we used an innovative normative modeling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertexwise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this, we employed a heterogeneous cross-sectional sample of 206 typically developing individuals (127 males) and 321 individuals with ASD (232 males) (6–31 years of age). Results: We found few case-control differences, but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing. Conclusions: Our results 1) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and 2) show that by focusing on common effects (i.e., the “average ASD participant”), the case-control approach disguises considerable interindividual variation crucial for precision medicine.
KW - Autism
KW - Cortical thickness
KW - Gaussian process
KW - Heterogeneity
KW - Normative modeling
KW - Outlier detection
UR - http://www.scopus.com/inward/record.url?scp=85061770618&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2018.11.013
DO - 10.1016/j.bpsc.2018.11.013
M3 - Article
AN - SCOPUS:85061770618
VL - 4
SP - 567
EP - 578
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
SN - 2451-9022
IS - 6
ER -