BRAIN PH IS DECREASED IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A META-ANALYSIS OF POSTMORTEM STUDIES

Abstract Background 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 consistently been observed in individuals with schizophrenia and bipolar disorder compared with healthy controls. We have recently demonstrated that similar brain alterations are common in a wide range of animal models of neuropsychiatric disorders, including MDD. However, our understanding of brain pH alterations in human patients with MDD remains limited. Aims & Objectives In this study, we aimed to evaluate postmortem brain pH in patients with MDD in comparison to control subjects. Method We utilized publicly available data on brain pH to conduct a quantitative meta-analysis. Results The results of the random effects model, using 43 available datasets, indicated a decrease in brain pH in patients with MDD (Hedges’ g = -0.22, p = 0.0056). We also conducted a two-way analysis of covariance, with the dataset and diagnosis as the main factors, and postmortem interval, age at death, and sex as covariates. While significant effects were observed for the covariates, the effect of diagnosis remained significant. Discussion & Conclusion This study suggests a decrease in brain pH in patients with MDD, which could be a potential clue in understanding the pathophysiology. When combined with insights from animal model studies, it suggests that altered brain energy metabolism leading to decreased brain pH may serve as a potential transdiagnostic endophenotype for MDD and other neuropsychiatric disorders.