SynthesisNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders.
Synthesis in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
77 citing papers in PubMed, 4 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- Postmortem evidence of decreased brain pH in major depressive disorder: a systematic review and meta-analysis.Translational psychiatry · 2024Pooled it
- Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies.The international journal of neuropsychopharmacology · 2024Pooled it
- Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans.Translational psychiatry · 2020Pooled it
- Brain lactate and pH in schizophrenia and bipolar disorder: a systematic review of findings from magnetic resonance studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled it
- Altered Vascular and Angiogenic Transcripts in the Neurogenic Niche in Neuroinflammatory-Type Schizophrenia.Schizophrenia bulletin · 2026Article
- Inhibition of delta-1 glutamate receptor current by extracellular protons.bioRxiv : the preprint server for biology · 2026Article
- Lactate-Mediated Brain Acidosis Drives Epigenetic Dysregulation of TGFB2 and Associated Gene Networks in Schizophrenia and Bipolar Disorder.International journal of molecular sciences · 2026Article
- Transcriptomic analysis reveals synaptic dysregulation and mitochondrial dysfunction in autism spectrum disorder.Brain, behavior, & immunity - health · 2026Article
- Upregulation of DNA repair-related genes in the prefrontal cortex of patients with schizophrenia with low genetic risk.Schizophrenia (Heidelberg, Germany) · 2026Article
- Biomarkers associated with future suicide risk enhance predictive performance in psychiatric inpatients.BMJ health & care informatics · 2026Article
- Increased Tumor Necrosis Factor Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains.Biological psychiatry global open science · 2026Article
- Increased Cerebrospinal Fluid Lactate Levels in Schizophrenia and Major Depressive Disorder: NCNP Biobank Study in Japan.Neuropsychopharmacology reports · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- From metabolic substrate to epigenetic regulation: roles and mechanisms of lactylation in brain health and disease.Frontiers in molecular neuroscience · 2026Review
- Microglia-derived metabolites as novel signaling molecules: regulating neural circuit function, behavior, and their role in psychiatric disorders.Frontiers in cellular neuroscience · 2026Review
- New molecular markers to differentiate carbon dioxide intoxication from asphyxia due to oxygen deficiency.Forensic science, medicine, and pathology · 2025Article
- Dynamic control of NMDA receptor CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Remote spatial memory deficits in mouse models of neuropsychiatric disorders with immature dentate gyrus phenotype.The international journal of neuropsychopharmacology · 2025Article
- Impact of Confounding Factors in Human Postmortem Brain Tissues on Gene Expression Profiles: A Comparison of Patients With Schizophrenia, Bipolar Disorder, and Nonpsychiatric Controls.Neuropsychopharmacology reports · 2025Article
- RVG engineered extracellular vesicles-transmitted miR-137 improves autism by modulating glucose metabolism and neuroinflammation.Molecular psychiatry · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.