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Overlapping but asymmetrical relationships between schizophrenia and autism revealed by brain connectivity

Yujiro Yoshihara, Giuseppe Lisi, Noriaki Yahata, Junya Fujino, Yukiko Matsumoto, Jun Miyata, Genichi Sugihara, Shin-ichi Urayama, Manabu Kubota, Masahiro Yamashita, Ryuichiro Hashimoto, Naho Ichikawa, Weipke Cahn, Neeltje E. M. van Haren, Susumu Mori, Yasumasa Okamoto, Kiyoto Kasai, Nobumasa Kato, Hiroshi Imamizu, René S. Kahn, Akira Sawa, Mitsuo Kawato, Toshiya Murai, Jun Morimoto, Hidehiko Takahashi
doi: https://doi.org/10.1101/403212
Yujiro Yoshihara
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Giuseppe Lisi
2Department of Brain Robot Interface, ATR (Advanced Telecommunications Research Institute International) Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan
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Noriaki Yahata
3Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619–0288, Japan
4Department of Youth Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo 113–0033, Japan
5Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263–8555, Japan
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Junya Fujino
6Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan
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Yukiko Matsumoto
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Jun Miyata
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Genichi Sugihara
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Shin-ichi Urayama
7Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto 606- 8507, Japan
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Manabu Kubota
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
6Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan
8Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Masahiro Yamashita
9Department of Cognitive Neuroscience, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan
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Ryuichiro Hashimoto
3Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619–0288, Japan
6Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan
10Department of Language Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
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Naho Ichikawa
11Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Weipke Cahn
12Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Neeltje E. M. van Haren
12Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Susumu Mori
13Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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Yasumasa Okamoto
11Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Kiyoto Kasai
14Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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Nobumasa Kato
6Medical Institute of Developmental Disabilities Research, Showa University Karasuyama Hospital, Tokyo 157-8577, Japan
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Hiroshi Imamizu
9Department of Cognitive Neuroscience, ATR Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan
15Department of Psychology, Graduate School of Humanities and Sociology, The University of Tokyo, Tokyo 113-0033, Japan
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René S. Kahn
12Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Akira Sawa
16Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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Mitsuo Kawato
3Department of Decoded Neurofeedback, ATR Brain Information Communication Research Laboratory Group, Kyoto 619–0288, Japan
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Toshiya Murai
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Jun Morimoto
2Department of Brain Robot Interface, ATR (Advanced Telecommunications Research Institute International) Brain Information Communication Research Laboratory Group, Kyoto 619-0288, Japan
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Hidehiko Takahashi
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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  • For correspondence: hidehiko@kuhp.kyoto-u.ac.jp
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(Abstract included 248 words)

Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. To address this issue, we took advantage of dual (ASD and SSD) classifiers that discriminate patients from their controls based on resting state brain functional connectivity. An SSD classifier using sophisticated machine-learning algorithms that automatically selected SSD- specific functional connections was applied to Japanese datasets including adult patients with SSD in a chronic stage. We demonstrated good performance of the SSD classification for independent validation cohorts. The generalizability was tested by USA and European cohorts in a chronic stage, and one USA cohort including first episode schizophrenia. The specificity was tested by two adult Japanese cohorts of ASD and major depressive disorder, and one European cohort of attention-deficit hyperactivity disorder. The weighted linear summation of the classifier’s functional connections constituted the biological dimensions representing neural liability to the disorders. Our previously developed robust ASD classifier constituted the ASD dimension. Distributions of individuals with SSD, ASD and healthy controls were examined on the SSD and ASD biological dimensions. The SSD and ASD populations exhibited overlapping but asymmetrical patterns on the two biological dimensions. That is, the SSD population showed increased liability on the ASD dimension, but not vice versa. Furthermore, the two dimensions were correlated within the ASD population but not the SSD population. Using the two biological dimensions based on resting-state functional connectivity enabled us to quantify and visualize the relationships between SSD and ASD.

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Posted September 07, 2018.
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Overlapping but asymmetrical relationships between schizophrenia and autism revealed by brain connectivity
Yujiro Yoshihara, Giuseppe Lisi, Noriaki Yahata, Junya Fujino, Yukiko Matsumoto, Jun Miyata, Genichi Sugihara, Shin-ichi Urayama, Manabu Kubota, Masahiro Yamashita, Ryuichiro Hashimoto, Naho Ichikawa, Weipke Cahn, Neeltje E. M. van Haren, Susumu Mori, Yasumasa Okamoto, Kiyoto Kasai, Nobumasa Kato, Hiroshi Imamizu, René S. Kahn, Akira Sawa, Mitsuo Kawato, Toshiya Murai, Jun Morimoto, Hidehiko Takahashi
bioRxiv 403212; doi: https://doi.org/10.1101/403212
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Overlapping but asymmetrical relationships between schizophrenia and autism revealed by brain connectivity
Yujiro Yoshihara, Giuseppe Lisi, Noriaki Yahata, Junya Fujino, Yukiko Matsumoto, Jun Miyata, Genichi Sugihara, Shin-ichi Urayama, Manabu Kubota, Masahiro Yamashita, Ryuichiro Hashimoto, Naho Ichikawa, Weipke Cahn, Neeltje E. M. van Haren, Susumu Mori, Yasumasa Okamoto, Kiyoto Kasai, Nobumasa Kato, Hiroshi Imamizu, René S. Kahn, Akira Sawa, Mitsuo Kawato, Toshiya Murai, Jun Morimoto, Hidehiko Takahashi
bioRxiv 403212; doi: https://doi.org/10.1101/403212

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