Publication Name	World Journal of Biological Chemistry
Manuscript ID	124867
DOI	10.4331/wjbc.124867
Country	Japan

Category	Psychiatry
Manuscript Type	Minireviews
Article Title	Molecular hydrogen therapy in schizophrenia: A translational review for treatment resistance
Manuscript Source	Invited Manuscript
All Author List	Takahiko Nagamine
Funding Agency and Grant Number
Corresponding Author	Takahiko Nagamine, MD, PhD, Professor Emeritus, Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, Hofu 747-0066, Japan. tnagamine@outlook.com
Key Words	Schizophrenia; Hydrogen gas; Oxidative stress; Neuroprogression; Treatment-resistant schizophrenia; Translational psychiatry; Dose optimization; Neuroprotection
Core Tip	Oxidative neuroprogression and N-methyl-D-aspartate receptor hypofunction represent a critical pathophysiological hub in schizophrenia that remains unaddressed by standard D2-receptor-antagonist antipsychotics, leading to high rates of treatment resistance. Molecular hydrogen (H2) offers a unique, highly diffusible, and selective antioxidant intervention. Recent preclinical work reveals that while H2 gas inhalation successfully achieves central target engagement by completely restoring whole-brain hydroxyl radical antioxidant capacity, it may fail to rescue hyperlocomotion or sensorimotor gating deficits at a single fixed dose. This minireview highlights the critical need for dose-response optimization, arguing that the non-linear pharmacology of medical gases dictates systematic multi-dose evaluation. Positioned as an early adjunctive intervention, H2 therapy holds immense translational promise to halt oxidative cascade injuries and reshape the therapeutic paradigm for refractory psychiatric conditions.
Citation	Nagamine T. Molecular hydrogen therapy in schizophrenia: A translational review for treatment resistance. World J Biol Chem 2026; In press DOI: https://doi.org/10.4331/wjbc.124867
PDF	124867-in-press.pdf

Received	2026-06-25 02:25
Peer-Review Started	2026-06-25 02:26
First Decision by Editorial Office Director
Return for Revision	2026-07-23 06:03
Revised	2026-07-24 03:07
Publication Fee Transferred
Second Decision by Editor	2026-09-09 02:32
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-09-09 10:28
Articles in Press	2026-09-09 10:28
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1949-8454 (online)
Open Access	Open-Access: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
Copyright	©Author(s) (or their employer(s)) 2026. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
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