Abstract
Background
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized
by substantial clinical and biological heterogeneity. Quantitative and individualized
metrics for delineating the heterogeneity of brain structure in ASD are still lacking.
Likewise, the extent to which brain structural metrics of ASD deviate from typical
development (TD) and whether deviations can be used for parsing brain structural phenotypes
of ASD is unclear.
Methods
T1-weighted magnetic resonance imaging data from the Autism Brain Imaging Data Exchange
(ABIDE) II (nTD = 564) were used to generate a normative model to map brain structure deviations
of ABIDE I subjects (nTD = 560, nASD = 496). Voxel-based morphometry was used to compute gray matter volume. Non-negative
matrix factorization was employed to decompose the gray matter matrix into 6 factors
and weights. These weights were used for normative modeling to estimate the factor
deviations. Then, clustering analysis was used to identify ASD subtypes.
Results
Compared with TD, ASD showed increased weights and deviations in 5 factors. Three
subtypes with distinct neuroanatomical deviation patterns were identified. ASD subtype
1 and subtype 3 showed positive deviations, whereas ASD subtype 2 showed negative
deviations. Distinct clinical manifestations in social communication deficits were
identified among the three subtypes.
Conclusions
Our findings suggest that individuals with ASD have heterogeneous deviation patterns
in brain structure. The results highlight the need to test for subtypes in neuroimaging
studies of ASD. This study also presents a framework for understanding neuroanatomical
heterogeneity in this increasingly prevalent neurodevelopmental disorder.
Keywords
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Article info
Publication history
Published online: January 27, 2022
Accepted:
January 14,
2022
Received in revised form:
December 28,
2021
Received:
August 11,
2021
Identification
Copyright
© 2022 Society of Biological Psychiatry.
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- Disentangling the Heterogeneity of Autism Spectrum Disorder Using Normative ModelingBiological PsychiatryVol. 91Issue 11
- PreviewAutism spectrum disorder (ASD) is a pervasive and complex developmental condition that has shown significant heterogeneity in genetic vulnerability, etiology, phenotype, and outcome (1). Its heterogeneity continues to be a major barrier in understanding the neurobiological processes underlying ASD and developing individualized treatment for ASD. Extensive efforts to parse the heterogeneity of ASD over the past decade have had limited yield despite the use of a broad array of approaches. These efforts are further confounded by recent changes in the diagnostic classification of ASD, which was an earlier attempt to disentangle the heterogeneity of ASD.
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