TY - JOUR
T1 - Generalizable and transportable resting-state neural signatures characterized by functional networks, neurotransmitters, and clinical symptoms in autism
AU - Itahashi, Takashi
AU - Yamashita, Ayumu
AU - Takahara, Yuji
AU - Yahata, Noriaki
AU - Aoki, Yuta Y.
AU - Fujino, Junya
AU - Yoshihara, Yujiro
AU - Nakamura, Motoaki
AU - Aoki, Ryuta
AU - Okimura, Tsukasa
AU - Ohta, Haruhisa
AU - Sakai, Yuki
AU - Takamura, Masahiro
AU - Ichikawa, Naho
AU - Okada, Go
AU - Okada, Naohiro
AU - Kasai, Kiyoto
AU - Tanaka, Saori C.
AU - Imamizu, Hiroshi
AU - Kato, Nobumasa
AU - Okamoto, Yasumasa
AU - Takahashi, Hidehiko
AU - Kawato, Mitsuo
AU - Yamashita, Okito
AU - Hashimoto, Ryu Ichiro
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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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U2 - 10.1038/s41380-024-02759-3
DO - 10.1038/s41380-024-02759-3
M3 - Article
AN - SCOPUS:85205235050
SN - 1359-4184
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -