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Transdiagnostic characterization of neuropsychiatric disorders by hyperexcitation-induced immaturity

View ORCID ProfileTomoyuki Murano, View ORCID ProfileHideo Hagihara, Katsunori Tajinda, Mitsuyuki Matsumoto, View ORCID ProfileTsuyoshi Miyakawa
doi: https://doi.org/10.1101/376962
Tomoyuki Murano
1Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Japan
2Department of Physiological Science, School of Life Science, The Graduate University for Advanced Studies, Japan [SOKENDAI]
3Division of Cell Signaling, National Institute for Physiological Sciences, Japan
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Hideo Hagihara
1Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Japan
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Katsunori Tajinda
4Neuroscience, La Jolla Laboratory, Astellas Research Institute of America LLC, USA
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Mitsuyuki Matsumoto
5Drug Discovery Research, Astellas Pharma Inc., Japan
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Tsuyoshi Miyakawa
1Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Japan
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  • ORCID record for Tsuyoshi Miyakawa
  • For correspondence: miyakawa@fujita-hu.ac.jp
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Abstract

Biomarkers are needed to improve the diagnosis of neuropsychiatric disorders. Promising candidates are imbalance of excitation and inhibition in the brain, and maturation abnormalities. Here, we characterized different disease conditions by mapping changes in the expression patterns of maturation-related genes whose expression was altered by experimental neural hyperexcitation in published studies. This revealed two gene expression patterns: decreases in maturity markers and increases in immaturity markers. These two groups of genes were characterized by the overrepresentation of genes related to synaptic function and chromosomal modification, respectively. We used these two groups in a transdiagnostic analysis of 80 disease datasets for eight neuropsychiatric disorders and 12 datasets from corresponding animal models, and found that transcriptomic pseudoimmaturity inducible by neural hyperexcitation is shared by multiple neuropsychiatric disorders, such as schizophrenia, Alzheimer disorders, and ALS. Our results indicate that this endophenotype serve as a basis for transdiagnostic characterization of these disorders.

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Posted July 30, 2018.
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Transdiagnostic characterization of neuropsychiatric disorders by hyperexcitation-induced immaturity
Tomoyuki Murano, Hideo Hagihara, Katsunori Tajinda, Mitsuyuki Matsumoto, Tsuyoshi Miyakawa
bioRxiv 376962; doi: https://doi.org/10.1101/376962
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Transdiagnostic characterization of neuropsychiatric disorders by hyperexcitation-induced immaturity
Tomoyuki Murano, Hideo Hagihara, Katsunori Tajinda, Mitsuyuki Matsumoto, Tsuyoshi Miyakawa
bioRxiv 376962; doi: https://doi.org/10.1101/376962

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