The association between plasma betaine level and brain structural changes in schizophrenia

Abstract Previous studies on metabolic profiling have shown decreased plasma levels of betaine in schizophrenia. Betaine serves as a substrate of betaine-homocysteine methyltransferase, which converts homocysteine to methionine. A decrease in betaine may lead to the elevation of homocysteine and an...

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Main Authors: Favour Omileke, Tempei Ikegame, Shimon Tonsho, Shunsuke Mori, Eimu Shoji, Masahiro Kiyota, Takuto Minami, Eureka Kumagai, Tatsuro Asai, Kenji Kirihara, Shinsuke Koike, Seiichiro Jinde, Kouhei Kamiya, Osamu Abe, Kiyoto Kasai, Naohiro Okada
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Schizophrenia
Online Access:https://doi.org/10.1038/s41537-025-00657-3
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author Favour Omileke
Tempei Ikegame
Shimon Tonsho
Shunsuke Mori
Eimu Shoji
Masahiro Kiyota
Takuto Minami
Eureka Kumagai
Tatsuro Asai
Kenji Kirihara
Shinsuke Koike
Seiichiro Jinde
Kouhei Kamiya
Osamu Abe
Kiyoto Kasai
Naohiro Okada
author_facet Favour Omileke
Tempei Ikegame
Shimon Tonsho
Shunsuke Mori
Eimu Shoji
Masahiro Kiyota
Takuto Minami
Eureka Kumagai
Tatsuro Asai
Kenji Kirihara
Shinsuke Koike
Seiichiro Jinde
Kouhei Kamiya
Osamu Abe
Kiyoto Kasai
Naohiro Okada
author_sort Favour Omileke
collection DOAJ
description Abstract Previous studies on metabolic profiling have shown decreased plasma levels of betaine in schizophrenia. Betaine serves as a substrate of betaine-homocysteine methyltransferase, which converts homocysteine to methionine. A decrease in betaine may lead to the elevation of homocysteine and an insufficient supply of methyl donors, which may affect DNA methylation. To explore how decreased betaine levels could affect brain structural changes often observed in schizophrenia, the present study investigated the relationships in 27 patients with chronic schizophrenia and 49 healthy comparison individuals. We found that the effects of betaine on brain volume are group-specific, and significant correlations between betaine and notable brain areas implicated in schizophrenia’s pathophysiology including the superior temporal gyrus. These findings suggest that betaine levels may contribute to aberrant structural changes in schizophrenia.
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series Schizophrenia
spelling doaj-art-9847b1cc6d544fae80d51661828b1bda2025-08-20T03:05:09ZengNature PortfolioSchizophrenia2754-69932025-08-011111910.1038/s41537-025-00657-3The association between plasma betaine level and brain structural changes in schizophreniaFavour Omileke0Tempei Ikegame1Shimon Tonsho2Shunsuke Mori3Eimu Shoji4Masahiro Kiyota5Takuto Minami6Eureka Kumagai7Tatsuro Asai8Kenji Kirihara9Shinsuke Koike10Seiichiro Jinde11Kouhei Kamiya12Osamu Abe13Kiyoto Kasai14Naohiro Okada15Department of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoCenter for Evolutionary Cognitive Sciences, Graduate School of Art and Sciences, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Radiology, Toho University Omori Medical CenterDepartment of Radiology, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoDepartment of Neuropsychiatry, Graduate School of Medicine, The University of TokyoAbstract Previous studies on metabolic profiling have shown decreased plasma levels of betaine in schizophrenia. Betaine serves as a substrate of betaine-homocysteine methyltransferase, which converts homocysteine to methionine. A decrease in betaine may lead to the elevation of homocysteine and an insufficient supply of methyl donors, which may affect DNA methylation. To explore how decreased betaine levels could affect brain structural changes often observed in schizophrenia, the present study investigated the relationships in 27 patients with chronic schizophrenia and 49 healthy comparison individuals. We found that the effects of betaine on brain volume are group-specific, and significant correlations between betaine and notable brain areas implicated in schizophrenia’s pathophysiology including the superior temporal gyrus. These findings suggest that betaine levels may contribute to aberrant structural changes in schizophrenia.https://doi.org/10.1038/s41537-025-00657-3
spellingShingle Favour Omileke
Tempei Ikegame
Shimon Tonsho
Shunsuke Mori
Eimu Shoji
Masahiro Kiyota
Takuto Minami
Eureka Kumagai
Tatsuro Asai
Kenji Kirihara
Shinsuke Koike
Seiichiro Jinde
Kouhei Kamiya
Osamu Abe
Kiyoto Kasai
Naohiro Okada
The association between plasma betaine level and brain structural changes in schizophrenia
Schizophrenia
title The association between plasma betaine level and brain structural changes in schizophrenia
title_full The association between plasma betaine level and brain structural changes in schizophrenia
title_fullStr The association between plasma betaine level and brain structural changes in schizophrenia
title_full_unstemmed The association between plasma betaine level and brain structural changes in schizophrenia
title_short The association between plasma betaine level and brain structural changes in schizophrenia
title_sort association between plasma betaine level and brain structural changes in schizophrenia
url https://doi.org/10.1038/s41537-025-00657-3
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