ArticleMolecular psychiatry2024
The metabolic overdrive hypothesis: hyperglycolysis and glutaminolysis in bipolar mania.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Energy constraint on human health.Trends in endocrinology and metabolism: TEM · 2026Review
- NMR-based metabolic profiling in urine for bipolar disorder manic episode.Irish journal of medical science · 2026Article
- Differential protein network and biological functions atlas from multi-tissue proteomics in patients with depression.Molecular psychiatry · 2026Article
- Aerobic glycolysis in Schizophrenia: Developmental rescue or energetic breakdown?Molecular psychiatry · 2026Review
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Reconceptualizing bipolar disorder through an integrative biological lens: synthesis, convergence, and emerging directions.Frontiers in integrative neuroscience · 2026Review
- Clinical Insights Into the Mechanistic Crossroads of Lamotrigine and Therapeutic Ketosis in Bipolar Depression.Biological psychiatry global open science · 2026Review
- Cognitive behavioral therapy for bipolar disorder: patient-level participation barriers and ketogenic metabolic therapy as a candidate adjunct.Frontiers in psychology · 2026Review
- Comorbidity of undiagnosed mood symptoms with dementia risk in multi-regional multi-ethnic adults: evidence from epidemiological findings and plasma metabolites.Epidemiology and psychiatric sciences · 2025Article
- Allele-Specific Methylation Links Non-coding Variant of rs2280906 to MYOM2 Regulation in Schizophrenia.Molecular neurobiology · 2025Article
- The energy resistance principle.Cell metabolism · 2025Review
- Circadian rhythms in metabolism and mental health: a reciprocal regulatory network with implications for metabolic and neuropsychiatric disorders.Current opinion in physiology · 2025Review
- Glutamine Metabolism and Metabolic Profiling Using 7 T CRT-FID MRSI in Focal Epilepsy.European journal of neurology · 2025Article
- Bioenergetic biomarkers as predictive indicators and their relationship with cognitive function in newly diagnosed, drug-naïve patients with bipolar disorder.Translational psychiatry · 2025Article
- A pilot study of a ketogenic diet in bipolar disorder: clinical, metabolic and magnetic resonance spectroscopy findings.BJPsych open · 2025Article
- The role of β-hydroxybutyrate testing in ketogenic metabolic therapies.Frontiers in nutrition · 2025Review
- Article
- Stable-isotope tracing reveals the role of corticosteroid receptors in driving cortisol-mediated central and peripheral glucose regulation in zebrafish.Frontiers in endocrinology · 2025Article
- Breaking barriers: centering researchers with lived experience in psychiatric neuroscience.NPP - digital psychiatry and neuroscience · 2025Review
- Metabolic Insights into Neuropsychiatric Illnesses and Ketogenic Therapies: A Transcriptomic View.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evidence from diverse areas of research including chronobiology, metabolomics and magnetic resonance spectroscopy indicate that energy dysregulation is a central feature of bipolar disorder pathophysiology. In this paper, we propose that mania represents a condition of heightened cerebral energy metabolism facilitated by hyperglycolysis and glutaminolysis. When oxidative glucose metabolism becomes impaired in the brain, neurons can utilize glutamate as an alternative substrate to generate energy through oxidative phosphorylation. Glycolysis in astrocytes fuels the formation of denovo glutamate, which can be used as a mitochondrial fuel source in neurons via transamination to alpha-ketoglutarate and subsequent reductive carboxylation to replenish tricarboxylic acid cycle intermediates. Upregulation of glycolysis and glutaminolysis in this manner causes the brain to enter a state of heightened metabolism and excitatory activity which we propose to underlie the subjective experience of mania. Under normal conditions, this mechanism serves an adaptive function to transiently upregulate brain metabolism in response to acute energy demand. However, when recruited in the long term to counteract impaired oxidative metabolism it may become a pathological process. In this article, we develop these ideas in detail, present supporting evidence and propose this as a novel avenue of investigation to understand the biological basis for mania.
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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.