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Gray matter asymmetry alterations in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder

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Abstract

Despite the high coexistence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) (ASD + ADHD), the underlying neurobiological basis of this disorder remains unclear. Altered brain structural asymmetries have been verified in ASD and ADHD, respectively, making brain asymmetry a candidate for characterizing this coexisting disorder. Here, we measured the gray matter (GM) volume asymmetry in ASD + ADHD versus ASD without ADHD (ASD-only), ADHD without ASD (ADHD-only), and typically developing controls (TDc). High-resolution T1-weighted data from 48 ASD + ADHD, 63 ASD-only, 32 ADHD-only, and 211 matched TDc were included in our study. We also assessed brain-behavior relationships and the effects of age on GM asymmetry. We found that there were both shared and disorder-specific GM volume asymmetry alterations in ASD + ADHD, ASD-only, and ADHD-only compared with TDc. This finding demonstrates that ASD + ADHD is neither an endophenocopy nor an additive pathology of ASD and ADHD, but an entirely different neuroanatomical pathology. In addition, ASD + ADHD displayed altered GM volume asymmetries in the prefrontal regions responsible for executive function and theory of mind compared with ASD-only. We also found significant effects of age on GM asymmetry. The present study may provide structural insights into the neural basis of ASD + ADHD.

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Data availability

The data used in our study were obtained from the ABIDE database and the ADHD-200 Sample database and are publicly available at http://fcon_1000.projects.nitrc.org/indi/abide/ and http://fcon_1000.projects.nitrc.org/indi/adhd200/.

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Acknowledgements

We would like to express our sincere appreciation to the data donors and organizers and participants who participated in this study and to Dr. Gao Lei from Zhongnan Hospital of Wuhan University for his guidance on image processing technology.

Funding

National Natural Science Foundation Of China, 81871354, 81571672,81871354, 81571672,81871354, 81571672,81871354, 81571672, 81871354, 81571672,81871354, 81571672,81871354, 81571672

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Authors and Affiliations

  1. Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, China

    Cuicui Li, Yunna Zhou, Tong Li, Rui Qin, Lin Li, Xianshun Yuan & Ximing Wang

  2. Department of Radiology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No.1 Jingba Road, Jinan, 250021, Shandong, China

    Rui Zhang

  3. Physical Examination Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Jinan, 250021, Shandong, China

    Li Wang

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  1. Cuicui Li
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Contributions

XMW, LW, and XSY gain research funding. CCL, XMW, LW, and XSY contributed to the study design, interpretation of the findings, and manuscript edits. CCL wrote the initial draft of the manuscript.CCL, XMW, LW, XSY, YNZ, RZ, RQ, TL, and LL supervised the analysis of study data. CCL, XMW, LW, XSY, YNZ, RZ, RQ, TL, and LL collected the data. YNZ, RZ, RQ, TL, and LL performed data cleaning and analysis.

Corresponding authors

Correspondence to Xianshun Yuan, Li Wang or Ximing Wang.

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The authors declare no conflicts of interest.

Ethical approval

All subjects and/or carers provided informed consent. Experiments were approved by the Institutional Review Board at each site.

Supplementary Information

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Supplementary file1 (DOCX 28 KB)

Supplementary file2 (DOCX 19 KB)

787_2023_2323_MOESM3_ESM.tif

Supplementary file3 Supplementary Figure 1 Tissue segmentation. Shown are three examples of successful tissue segmentations. Each example of an original T1-weighted image, two main tissue compartments resulting from the segmentation step: gray matter and white matter, and an overall weighted image quality rating. Abbreviations: GM gray matter, WM white matter (TIF 8207 KB)

787_2023_2323_MOESM4_ESM.jpg

Supplementary file4 Supplementary Figure 2 Calculation of AIs. AI= ((i1-i2)/((i1+i2).*0.5)).*i3, where i1 refers to the nonflipped warped GM segments, i2 refers to the flipped warped GM segments, and i3 refers to the right-hemispheric mask image. Due to the use of the right hemisphere mask, for all nonflipped and flipped warped GM segments, only the right hemisphere is retained for further analysis. The “i1-i2” in the right hemisphere represents ‘‘right-minus-left asymmetry. Therefore, positive AIs represent rightward GM volume asymmetry and negative AIs represent leftward GM volume asymmetry, respectively. Abbreviations: AI asymmetry index, GM gray matter, WM white matter (JPG 115 KB)

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Li, C., Zhang, R., Zhou, Y. et al. Gray matter asymmetry alterations in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry (2023). https://doi.org/10.1007/s00787-023-02323-4

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