Postmortem evidence of decreased brain pH in major depressive disorder: a systematic review and meta-analysis.

IF 5.8 1区 医学 Q1 PSYCHIATRY
Hideo Hagihara, Tsuyoshi Miyakawa
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引用次数: 0

Abstract

Introduction: Major depressive disorder (MDD) is a prevalent and debilitating mental disorder that shares symptoms, genetics, and molecular changes in the brain with other psychiatric disorders, such as schizophrenia and bipolar disorder. Decreased brain pH, associated with increased lactate levels due to altered energy metabolism and neuronal hyperexcitation, has been consistently observed in schizophrenia and bipolar disorder. We recently demonstrated similar brain alterations in various animal models of neuropsychiatric disorders, including MDD. However, our understanding of brain pH alterations in human patients with MDD remains limited.

Methods: We conducted meta-analyses to assess postmortem brain pH in patients with MDD compared to control subjects, examining its relationships with recurrence of depressive episodes and illness duration, utilizing publicly available demographic data. Studies reporting individual raw pH data were identified through searches in the Stanley Medical Research Institute database, NCBI GEO database, PubMed, and Google Scholar. The data were analyzed using the random effects model, ANOVA, and ANCOVA.

Results: The random effects model, using 39 curated datasets (790 patients and 957 controls), indicated a significant decrease in brain pH in patients with MDD (Hedges' g = -0.23, p = 0.0056). A two-way ANCOVA revealed that the effect of diagnosis on pH remained significant when considering covariates, including postmortem interval, age at death, and sex. Patients with recurrent episodes, but not a single episode, showed significantly lower pH than controls in both females and males (256 patients and 279 controls from seven datasets). Furthermore, a significant negative correlation was observed between brain pH and illness duration (115 patients from five datasets). Female preponderance of decreased pH was also found, possibly due to a longer illness duration and a higher tendency of recurrent episodes in females.

Conclusion: This study suggests a decrease in brain pH in patients with MDD, potentially associated with recurrent episodes and longer illness duration. As suggested from previous animal model studies, altered brain energy metabolism, leading to decreased pH, may serve as a potential transdiagnostic endophenotype for MDD and other neuropsychiatric disorders.

重度抑郁症患者大脑 pH 值降低的尸检证据:系统回顾和荟萃分析。
简介重度抑郁障碍(MDD)是一种普遍存在且使人衰弱的精神疾病,它与精神分裂症和双相情感障碍等其他精神疾病具有相同的症状、遗传学和大脑分子变化。在精神分裂症和躁狂症中,一直都能观察到脑pH值降低,这与能量代谢改变和神经元过度兴奋导致的乳酸水平升高有关。最近,我们在包括 MDD 在内的多种神经精神疾病动物模型中也发现了类似的脑部变化。然而,我们对人类 MDD 患者大脑 pH 值变化的了解仍然有限:我们进行了荟萃分析,评估了与对照组相比,多发性抑郁症患者死后大脑的 pH 值,并利用公开的人口统计学数据研究了其与抑郁发作复发和病程的关系。通过在斯坦利医学研究所数据库、NCBI GEO 数据库、PubMed 和谷歌学术中搜索,确定了报告个人原始 pH 值数据的研究。采用随机效应模型、方差分析和方差分析对数据进行了分析:随机效应模型使用了 39 个数据集(790 名患者和 957 名对照组),结果表明 MDD 患者的大脑 pH 值显著下降(Hedges' g = -0.23,p = 0.0056)。双向方差分析显示,当考虑到包括死后间隔、死亡年龄和性别在内的协变量时,诊断对pH值的影响仍然显著。在女性和男性中,反复发作而非单次发作的患者的pH值明显低于对照组(七个数据集中的256名患者和279名对照组)。此外,还观察到大脑 pH 值与病程之间存在明显的负相关(5 个数据集中的 115 名患者)。研究还发现,pH值降低的患者以女性居多,这可能是由于女性患者的病程较长,且更容易反复发作:这项研究表明,多发性硬化症患者大脑pH值降低,可能与反复发作和病程较长有关。正如之前的动物模型研究表明的那样,脑能量代谢的改变导致pH值下降,这可能是MDD和其他神经精神疾病的一种潜在的跨诊断内表型。
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
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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