Division of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Japan.
Transl Psychiatry. 2024 Nov 4;14(1):460. doi: 10.1038/s41398-024-03173-7.
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.
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.
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.
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（MDD）是一种常见且使人虚弱的精神障碍，其症状、遗传学和大脑中的分子变化与其他精神疾病（如精神分裂症和双相情感障碍）相似。由于能量代谢改变和神经元过度兴奋，导致乳酸水平升高，大脑 pH 值降低，这在精神分裂症和双相情感障碍中一直存在。我们最近在各种神经精神疾病的动物模型中也观察到了类似的大脑改变，包括 MDD。然而，我们对 MDD 患者大脑 pH 值改变的了解仍然有限。
我们通过在 Stanley 医学研究所数据库、NCBI GEO 数据库、PubMed 和 Google Scholar 中搜索，确定了研究报道的个体原始 pH 值数据，然后进行了荟萃分析，以评估 MDD 患者与对照组的死后大脑 pH 值，并利用公开的人口统计学数据检查其与抑郁发作复发和疾病持续时间的关系。使用随机效应模型、方差分析和协方差分析对数据进行了分析。
使用 39 个经过精心整理的数据集（790 名患者和 957 名对照）的随机效应模型表明，MDD 患者的大脑 pH 值显著降低（Hedges' g = -0.23，p = 0.0056）。双向协方差分析显示，在考虑包括死后间隔、死亡时年龄和性别在内的协变量后，诊断对 pH 值的影响仍然显著。与对照组相比，有复发性发作的患者（来自七个数据集的 256 名患者和 279 名对照），而非单次发作的患者，其 pH 值明显更低，而且无论男女都存在这种情况（来自七个数据集的 256 名患者和 279 名对照）。此外，还观察到大脑 pH 值与疾病持续时间之间存在显著的负相关关系（来自五个数据集的 115 名患者）。女性 pH 值降低的倾向性也得到了证实，这可能是由于女性的疾病持续时间较长，以及更倾向于出现复发性发作。
这项研究表明，MDD 患者的大脑 pH 值降低，可能与复发性发作和疾病持续时间延长有关。正如以前的动物模型研究所表明的，改变的大脑能量代谢导致 pH 值降低，可能是 MDD 和其他神经精神疾病的潜在跨诊断表型。
