Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan

Miyamoto, Tesshin; Mori, Kohji; Akamine, Shoshin; Kondo, Shizuko; Gotoh, Shiho; Uozumi, Ryota; Umeda, Sumiyo; Koguchi-Yoshioka, Hanako; Nojima, Satoshi; Taomoto, Daiki; Satake, Yuto; Suehiro, Takashi; Kanemoto, Hideki; Yoshiyama, Kenji; Morihara, Takashi; Ikeda, Manabu

doi:https://doi.org/10.1111/pcn.13854

Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan

Miyamoto, Tesshin; Mori, Kohji; Akamine, Shoshin et al.

Psychiatry and Clinical Neurosciences, 2025

Number of Access:58（2025-08-14 04:43 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102240

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Title	Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan
Creator	CreatorName Miyamoto, Tesshin
	NRID 1000040775318 1000040775318 ORCID 0000-0003-2629-0723 0000-0003-2629-0723 researchmap permalink kmori_psy kmori_psy Scopus Author ID 55579363000 55579363000 CreatorName Mori, Kohji
	NRID 1000000846222 1000000846222 ORCID 0000-0001-6476-6222 0000-0001-6476-6222 researchmap permalink shak shak Scopus Author ID 57219991127 57219991127 CreatorName Akamine, Shoshin
	CreatorName Kondo, Shizuko
	CreatorName Gotoh, Shiho
	CreatorName Uozumi, Ryota
	CreatorName Umeda, Sumiyo
	NRID 1000060714269 1000060714269 ORCID 0000-0002-3415-5727 0000-0002-3415-5727 researchmap permalink hanyos hanyos Scopus Author ID 55859761100 55859761100 CreatorName Koguchi-Yoshioka, Hanako
	NRID 1000040528791 1000040528791 ORCID 0000-0002-5124-0026 0000-0002-5124-0026 researchmap permalink snojima snojima Scopus Author ID 16224082000 16224082000 CreatorName Nojima, Satoshi
	NRID 1000060906725 1000060906725 ORCID 0009-0006-0578-2517 0009-0006-0578-2517 researchmap permalink taomotodaiki taomotodaiki Scopus Author ID 57328426900 57328426900 CreatorName Taomoto, Daiki
	ORCID 0000-0002-9350-3162 0000-0002-9350-3162 researchmap permalink y.satake y.satake Scopus Author ID 57218214023 57218214023 CreatorName Satake, Yuto
	NRID 1000030866611 1000030866611 researchmap permalink suehiro-takashi suehiro-takashi Scopus Author ID 57190874433 57190874433 CreatorName Suehiro, Takashi
	NRID 1000020838932 1000020838932 ORCID 0000-0003-3662-1469 0000-0003-3662-1469 researchmap permalink hkane_gerpsy hkane_gerpsy Scopus Author ID 56521238700 56521238700 CreatorName Kanemoto, Hideki
	NRID 1000020426498 1000020426498 researchmap permalink kenyoshiyama kenyoshiyama Scopus Author ID 55758733500 55758733500 CreatorName Yoshiyama, Kenji
	CreatorName Morihara, Takashi
	NRID 1000060284395 1000060284395 researchmap permalink manabu_ikeda manabu_ikeda Scopus Author ID 7404692889 7404692889 CreatorName Ikeda, Manabu
Subject	neurodegenerative disease
	Neuronal Intranuclear Inclusion Disease
	NOTCH2NLC
	repeat disease
	repeat primed PCR
Description	Miyamoto T., Mori K., Akamine S., et al. Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan. Psychiatry and Clinical Neurosciences , (2025); https://doi.org/10.1111/pcn.13854.
Abstract	Aim: A GGC repeat expansion in the 5′ untranslated region of NOTCH2NLC is a genetic cause of Neuronal Intranuclear Inclusion Disease (NIID) that exhibits cognitive, motor, and autonomic dysfunction. Our objective is to determine whether there are undiagnosed NIID cases in a psychiatry-based dementia-enriched cohort and to identify their clinical characteristics. Methods: A retrospective clinical cohort study was conducted in an inpatient and outpatient psychiatric clinic in a University Hospital in Osaka, Japan. Genomic DNA and clinical information were collected with written informed consent. Nine hundred fifty-eight cases were clinically classified according to the International Classification of Diseases (ICD)-10 system. Genetic analysis with Repeat-Primed PCR and Amplicon-Length PCRs were performed. Results: Of the 958 cases, three were confirmed to have an aberrant GGC repeat expansion in NOTCH2NLC. Cases 1 and 2 had preceding anxiety and depressive episodes, and one of these cases also had a mild cognitive impairment. Case 3 met the diagnostic criteria for progressive supranuclear palsy. All three cases lacked hyperintensity at the corticomedullary border on diffusion-weighted MRI, which is known as a characteristic for NIID. Interestingly, one case exhibited the corticomedullary hyperintensity later in the disease course with apparent neurocognitive decline. All three cases exhibited a mix of slow waves in electroencephalogram and elevated total protein level in cerebrospinal fluid. Conclusions: NIID is a rare cause of cognitive dysfunction in a psychiatry-based dementia-enriched cohort in Japan. Our data implicates psychiatric symptoms can be prodromal or early manifestation of a subset of NIID cases, thereby extending its phenotypic spectrum.
Publisher	John Wiley and Sons Inc
Source Title	Psychiatry and Clinical Neurosciences
Date of Issued	2025-07-14
Language	English
Handle URL	https://hdl.handle.net/11094/102240
PISSN	13231316
eISSN	14401819
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1111/pcn.13854
Access Rights	open access
CopyRight	© 2025 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Psychiatry and Clinical Neurosciences. 2025
DC.title	Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan
DC.creator	Miyamoto, Tesshin
	Mori, Kohji
	Akamine, Shoshin
	Kondo, Shizuko
	Gotoh, Shiho
	Uozumi, Ryota
	Umeda, Sumiyo
	Koguchi-Yoshioka, Hanako
	Nojima, Satoshi
	Taomoto, Daiki
	Satake, Yuto
	Suehiro, Takashi
	Kanemoto, Hideki
	Yoshiyama, Kenji
	Morihara, Takashi
	Ikeda, Manabu
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-14
DC.identifier	https://doi.org/10.1111/pcn.13854
DC.subject	neurodegenerative disease
	Neuronal Intranuclear Inclusion Disease
	NOTCH2NLC
	repeat disease
	repeat primed PCR
DC.description	Miyamoto T., Mori K., Akamine S., et al. Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan. Psychiatry and Clinical Neurosciences , (2025); https://doi.org/10.1111/pcn.13854.
DCTERMS.abstract	Aim: A GGC repeat expansion in the 5′ untranslated region of NOTCH2NLC is a genetic cause of Neuronal Intranuclear Inclusion Disease (NIID) that exhibits cognitive, motor, and autonomic dysfunction. Our objective is to determine whether there are undiagnosed NIID cases in a psychiatry-based dementia-enriched cohort and to identify their clinical characteristics. Methods: A retrospective clinical cohort study was conducted in an inpatient and outpatient psychiatric clinic in a University Hospital in Osaka, Japan. Genomic DNA and clinical information were collected with written informed consent. Nine hundred fifty-eight cases were clinically classified according to the International Classification of Diseases (ICD)-10 system. Genetic analysis with Repeat-Primed PCR and Amplicon-Length PCRs were performed. Results: Of the 958 cases, three were confirmed to have an aberrant GGC repeat expansion in NOTCH2NLC. Cases 1 and 2 had preceding anxiety and depressive episodes, and one of these cases also had a mild cognitive impairment. Case 3 met the diagnostic criteria for progressive supranuclear palsy. All three cases lacked hyperintensity at the corticomedullary border on diffusion-weighted MRI, which is known as a characteristic for NIID. Interestingly, one case exhibited the corticomedullary hyperintensity later in the disease course with apparent neurocognitive decline. All three cases exhibited a mix of slow waves in electroencephalogram and elevated total protein level in cerebrospinal fluid. Conclusions: NIID is a rare cause of cognitive dysfunction in a psychiatry-based dementia-enriched cohort in Japan. Our data implicates psychiatric symptoms can be prodromal or early manifestation of a subset of NIID cases, thereby extending its phenotypic spectrum.
DC.rights	© 2025 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	102240
citation_title	Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan
citation_author	Miyamoto, Tesshin
	Mori, Kohji
	Akamine, Shoshin
	Kondo, Shizuko
	Gotoh, Shiho
	Uozumi, Ryota
	Umeda, Sumiyo
	Koguchi-Yoshioka, Hanako
	Nojima, Satoshi
	Taomoto, Daiki
	Satake, Yuto
	Suehiro, Takashi
	Kanemoto, Hideki
	Yoshiyama, Kenji
	Morihara, Takashi
	Ikeda, Manabu
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2025-07-14
citation_journal_title	Psychiatry and Clinical Neurosciences
citation_doi	https://doi.org/10.1111/pcn.13854
citation_public_url	https://hdl.handle.net/11094/102240

Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan

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