Magnetic Resonance Spectroscopy Studies of Brain Energy Metabolism in Schizophrenia: Progression from Prodrome to Chronic Psychosis.

IF 5.5 2区 医学 Q1 PSYCHIATRY
Current Psychiatry Reports Pub Date : 2023-11-01 Epub Date: 2023-10-09 DOI:10.1007/s11920-023-01457-1
Abigail Stein, Chenyanwen Zhu, Fei Du, Dost Öngür
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Abstract

Purpose of review: Schizophrenia (SZ) is a debilitating mental illness; existing treatments are partially effective and associated with significant side effect burden, largely due to our limited understanding of disease mechanisms and the trajectory of disease progression. Accumulating evidence suggests that metabolic changes associated with glucose metabolism, mitochondrial dysfunction, and redox imbalance play an important role in the pathophysiology of schizophrenia. However, the molecular mechanisms associated with these abnormalities in the brains of schizophrenia patients and the ways in which they change over time remain unclear. This paper aims to review the current literature on molecular mechanisms and in vivo magnetic resonance spectroscopy (MRS) studies of impaired energy metabolism in patients at clinical high risk for psychosis, with first-episode SZ, and with chronic SZ. Our review covers research related to high-energy phosphate metabolism, lactate, intracellular pH, redox ratio, and the antioxidant glutathione.

Recent findings: Both first-episode and chronic SZ patients display a significant reduction in creatine kinase reaction activity and redox (NAD + /NADH) ratio in the prefrontal cortex. Chronic, but not first-episode, SZ patients also show a trend toward increased lactate levels and decreased pH value. These findings suggest a progressive shift from oxidative phosphorylation to glycolysis for energy production over the course of SZ, which is associated with redox imbalance and mitochondrial dysfunction. Accumulating evidence indicates that aberrant brain energy metabolism associated with mitochondrial dysfunction and redox imbalance plays a critical role in SZ and will be a promising target for future treatments.

Abstract Image

精神分裂症脑能量代谢的磁共振波谱研究:从前驱症状到慢性精神病的进展。
综述目的:精神分裂症是一种使人衰弱的精神疾病;现有的治疗方法部分有效,并伴有严重的副作用负担,这主要是由于我们对疾病机制和疾病进展轨迹的了解有限。越来越多的证据表明,与葡萄糖代谢、线粒体功能障碍和氧化还原失衡相关的代谢变化在精神分裂症的病理生理学中起着重要作用。然而,与精神分裂症患者大脑中这些异常相关的分子机制以及它们随时间变化的方式仍不清楚。本文旨在综述目前关于精神病临床高危患者、首发SZ患者和慢性SZ患者能量代谢受损的分子机制和体内磁共振波谱(MRS)研究的文献。我们的综述涵盖了与高能磷酸盐代谢、乳酸、细胞内pH、氧化还原比和抗氧化剂谷胱甘肽相关的研究。最近的发现:首发和慢性SZ患者的肌酸激酶反应活性和氧化还原(NAD + /NADH)比率。慢性但非首发的SZ患者也表现出乳酸水平升高和pH值降低的趋势。这些发现表明,在SZ过程中,能量产生从氧化磷酸化逐渐转变为糖酵解,这与氧化还原失衡和线粒体功能障碍有关。越来越多的证据表明,与线粒体功能障碍和氧化还原失衡相关的异常大脑能量代谢在SZ中起着关键作用,并将成为未来治疗的一个有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.30
自引率
3.00%
发文量
68
审稿时长
6-12 weeks
期刊介绍: This journal aims to review the most important, recently published research in psychiatry. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care of those affected by psychiatric disorders. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as anxiety, medicopsychiatric disorders, and schizophrenia and other related psychotic disorders. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.
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