Generalizable and transportable resting-state neural signatures characterized by functional networks, neurotransmitters, and clinical symptoms in autism

Autism spectrum disorder (ASD) is a lifelong condition with elusive biological mechanisms. The complexity of factors, including inter-site and developmental differences, hinders the development of a generalizable neuroimaging classifier for ASD. Here, we developed a classifier for ASD using a large-scale, multisite resting-state fMRI dataset of 730 Japanese adults, aiming to capture neural signatures that reflect pathophysiology at the functional network level, neurotransmitters, and clinical symptoms of the autistic brain. Our adult ASD classifier was successfully generalized to adults in the United States, Belgium, and Japan. The classifier further demonstrated its successful transportability to children and adolescents. The classifier contained 141 functional connections (FCs) that were important for discriminating individuals with ASD from typically developing controls. These FCs and their terminal brain regions were associated with difficulties in social interaction and dopamine and serotonin, respectively. Finally, we mapped attention-deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD) onto the biological axis defined by the ASD classifier. ADHD and SCZ, but not MDD, were located proximate to ASD on the biological dimensions. Our results revealed functional signatures of the ASD brain, grounded in molecular characteristics and clinical symptoms, achieving generalizability and transportability applicable to the evaluation of the biological continuity of related diseases.

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Publication Details

Journal
Molecular Psychiatry
Published
2024-09-28
DOI
https://doi.org/10.1038/s41380-024-02759-3
Citations
14
Primary Topic
EEG and Brain-Computer Interfaces
Type
article
Field-Weighted Citation Impact
4.80

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article

Generalizable and transportable resting-state neural signatures characterized by functional networks, neurotransmitters, and clinical symptoms in autism

Kiyoto Kasai, Noriaki Yahata, Naohiro Okada, Hiroshi Imamizu et al.
14 citations
Molecular Psychiatry
EEG and Brain-Computer Interfaces
4.80
article

Generalizable and transportable resting-state neural signatures characterized by functional networks, neurotransmitters, and clinical symptoms in autism

Kiyoto Kasai, Noriaki Yahata, Naohiro Okada, Hiroshi Imamizu, Saori Tanaka, Yujiro Yoshihara, Junya Fujino, Mitsuo Kawato, Masahiro Takamura, Hidehiko Takahashi, Okito Yamashita, Go Okada, Ryuta Aoki, Yuki Sakai, Ayumu Yamashita, Yasumasa Okamoto, Tsukasa Okimura, Naho Ichikawa, Takashi Itahashi, Yuji Takahara, Ryuichiro Hashimoto, Yuta Aoki, Motoaki Nakamura, Nobumasa Kato, Haruhisa Ohta
article en
14 citations

Abstract

Autism spectrum disorder (ASD) is a lifelong condition with elusive biological mechanisms. The complexity of factors, including inter-site and developmental differences, hinders the development of a generalizable neuroimaging classifier for ASD. Here, we developed a classifier for ASD using a large-scale, multisite resting-state fMRI dataset of 730 Japanese adults, aiming to capture neural signatures that reflect pathophysiology at the functional network level, neurotransmitters, and clinical symptoms of the autistic brain. Our adult ASD classifier was successfully generalized to adults in the United States, Belgium, and Japan. The classifier further demonstrated its successful transportability to children and adolescents. The classifier contained 141 functional connections (FCs) that were important for discriminating individuals with ASD from typically developing controls. These FCs and their terminal brain regions were associated with difficulties in social interaction and dopamine and serotonin, respectively. Finally, we mapped attention-deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD) onto the biological axis defined by the ASD classifier. ADHD and SCZ, but not MDD, were located proximate to ASD on the biological dimensions. Our results revealed functional signatures of the ASD brain, grounded in molecular characteristics and clinical symptoms, achieving generalizability and transportability applicable to the evaluation of the biological continuity of related diseases.

Molecular PsychiatryVol. 30(4)
Hiroshima University (JP), SHOWA Medical University (JP), Tokyo Medical and Dental University (JP), Chiba University (JP), Shimane University (JP), Kyoto University (JP), University of Shimane (JP), Advanced Telecommunications Research Institute International (JP), National Institutes for Quantum Science and Technology (JP), Shionogi (Japan) (JP), RIKEN Center for Advanced Intelligence Project (JP), Tokyo Metropolitan University (JP), The University of Tokyo (JP), Nara Institute of Science and Technology (JP), Futaba (Japan) (JP)
Leon Levy Foundation, Japan Agency for Medical Research and Development, Stavros Niarchos Foundation, University of Tokyo, Japan Society for the Promotion of Science, International Research Center for Neurointelligence, University of Tokyo, National Institute of Mental Health, Moonshot Research and Development Program
Openalex Percentile: Top 4%
EEG and Brain-Computer Interfaces
4.80
DOIOpen Access PDFOpenAlex
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