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. 2022 Jan;15(1):42-55.
doi: 10.1002/aur.2627. Epub 2021 Oct 27.

Dissecting the heterogeneous subcortical brain volume of autism spectrum disorder using community detection

Ting Li  1 , Martine Hoogman  1 , Nina Roth Mota  1 , Jan K Buitelaar  2 ; ENIGMA-ASD working group; Alejandro Arias Vasquez  1   3   2 , Barbara Franke  1   3 , Daan van Rooij  2
Affiliations

Dissecting the heterogeneous subcortical brain volume of autism spectrum disorder using community detection

Ting Li et al. Autism Res. 2022 Jan.

Abstract

Structural brain alterations in autism spectrum disorder (ASD) are heterogeneous, with limited effect sizes overall. In this study, we aimed to identify subgroups in ASD, based on neuroanatomical profiles; we hypothesized that the effect sizes for case/control differences would be increased in the newly defined subgroups. Analyzing a large data set from the ENIGMA-ASD working group (n = 2661), we applied exploratory factor analysis (EFA) to seven subcortical volumes of individuals with and without ASD to uncover the underlying organization of subcortical structures. Based on earlier findings and data availability, we focused on three age groups: boys (<=14 years), male adolescents (15-22 years), and adult men (> = 22 years). The resulting factor scores were used in a community detection (CD) analysis to cluster participants into subgroups. Three factors were found in each subsample; the factor structure in adult men differed from that in boys and male adolescents. From these factors, CD uncovered four distinct communities in boys and three communities in adolescents and adult men, irrespective of ASD diagnosis. The effect sizes for case/control comparisons were more pronounced than in the combined sample, for some communities. A significant group difference in ADOS scores between communities was observed in boys and male adolescents with ASD. We succeeded in stratifying participants into more homogeneous subgroups based on subcortical brain volumes. This stratification enhanced our ability to observe case/control differences in subcortical brain volumes in ASD, and may help to explain the heterogeneity of previous findings in ASD. LAY SUMMARY: Structural brain alterations in ASD are heterogeneous, with overall limited effect sizes. Here we aimed to identify subgroups in ASD based on neuroimaging measures. We tested whether the effect sizes for case/control differences would be increased in the newly defined subgroups. Based on neuroanatomical profiles, we succeeded in stratifying our participants into more homogeneous subgroups. The effect sizes of case/control differences were more pronounced in some subgroups than those in the whole sample.

Keywords: ASD; community detection; neuroanatomical heterogeneity; subcortical volume.

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Conflict of interest statement

Dr. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. Dr. Anagnostou has served as a consultant or advisory board member for Roche and Takeda. Dr. Freitag has served as a consultant for Desitin regarding issues on ASD. Dr. Rubia has received funding from Takeda pharmaceuticals for another project. Dr. Buitelaar has served as a consultant, advisory board member, or speaker for Eli Lilly, Janssen‐Cilag, Lundbeck, Medice, Novartis, Servier, Shire, and Roche, and he has received research support from Roche and Vifor. Dr. Gallagher received funding from the Meath Foundation and the National Children's Research Centre in Ireland. Dr. Parellada has served as a consultant, advisory board member, or received honoraria from Sevier and Exeltis. She has received travel support from Janssen Cilag and Lundbeck. Dr. Murphy has served on advisory boards for Roche and Servier. Dr. Franke has received educational speaking fees from Medice. The other authors report no financial relationships with commercial interests.

Figures

FIGURE 1
FIGURE 1
Schematic workflow of this study
FIGURE 2
FIGURE 2
The three‐factor model that was generated by EFA. (a) Boys. (b) Male adolescents. (c) Adult men
FIGURE 3
FIGURE 3
Subgroups generated by CD. (a) Boys. (b) Male adolescents. (c) Adult men. Lines represent participants in each community from CD. y‐axis indicates the mean factor scores for each factor. Error bars: SEM. *indicates case/control difference of subcortical factor scores was significant
FIGURE 4
FIGURE 4
Effect sizes of case/control comparison within each community and the whole subsample. (a) Boys. (b) Male adolescents. (c) Adult men. All: The whole subsample, 1: Community 1; 2: Community 2; 3: Community 3; 4: Community 4
See this image and copyright information in PMC

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