Palaniyappan Lena, Park Min Tae M, Jeon Peter, Limongi Roberto, Yang Kun, Sawa Akira, Théberge Jean
Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada.
Antioxidants (Basel). 2021 Oct 27;10(11):1703. doi: 10.3390/antiox10111703.
Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.
精神分裂症仍然是一种预后不良的疾病。大多数机制性变化发生在精神分裂症首次发作前许多年；疾病发作后这些变化不可逆转。一种在成年期仍可改变的发育机制可能以皮质内谷胱甘肽（GSH）为中心。大量临床前数据表明，精神分裂症患者亚组中存在显著谷胱甘肽缺乏的可能性。然而，关于皮质内谷胱甘肽的研究在这方面尚无定论。在本综述中，我们重点介绍了最近将谷胱甘肽与精神分裂症各个阶段的关键预后指标联系起来的超高场磁共振波谱研究。我们讨论了最终确定或反驳亚型持续性并阐明中枢抗氧化系统在精神分裂症早期破坏脑结构和连通性中作用所需的方法步骤。我们提议在即将开展的精神病抗氧化试验中对患者进行体内谷胱甘肽定量以进行患者选择。本综述为精神分裂症一种有前景的非多巴胺能早期干预方法提供了方向。
