Trial reportJournal of clinical psychopharmacology2017
Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.
Trial report in Journal of clinical psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- Glutamatergic and N-Acetylaspartate Metabolites in Bipolar Disorder: A Systematic Review and Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies.International journal of molecular sciences · 2022Pooled 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
- N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Linking Brain Morphometry to Psychometric Measures and Energy-Metabolic Biomarkers in Adults With Autism Spectrum Disorder.Autism research : official journal of the International Society for Autism Research · 2026Article
- Aerobic glycolysis in Schizophrenia: Developmental rescue or energetic breakdown?Molecular psychiatry · 2026Review
- Reconceptualizing bipolar disorder through an integrative biological lens: synthesis, convergence, and emerging directions.Frontiers in integrative neuroscience · 2026Review
- Neuroimaging evidence of mitochondrial dysfunction and inflammation in psychiatric disorders: a review.Psychoradiology · 2026Review
- Mitochondrial dysfunction in EEG: high-beta specific metabolic/oxidative coupling with lactate in mania-predominant polarity.Frontiers in psychiatry · 2026Article
- Neurometabolic predictors of mental effort in the frontal cortex.Translational psychiatry · 2025Article
- Enhanced detection of glutamate via transverse relaxation encoding with narrowband decoupling in the human brain.Magnetic resonance in medicine · 2025Article
- Serum lactate and LDH are related with theta and gamma activities in bipolar disorder: a band-specific metabolic coupling.Frontiers in psychiatry · 2025Article
- Lactate flux dysfunction in patients with bipolar disorder: preliminary insights from ultra-high field 7T MRSI during task and rest.Frontiers in neuroscience · 2025Article
- Exploring mitochondrial blood-based and genetic markers in older adults with mild cognitive impairment and remitted major depressive disorder.Translational psychiatry · 2024Article
- Prefrontal metabolite alterations in individuals with posttraumatic stress disorder: a 7T magnetic resonance spectroscopy study.bioRxiv : the preprint server for biology · 2024Article
- Article
- Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases.Biomedicines · 2024Review
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Lactate: A Theranostic Biomarker for Metabolic Psychiatry?Antioxidants (Basel, Switzerland) · 2023Review
- Functional Connectivity of the Cerebellar Vermis in Bipolar Disorder and Associations with Mood.bioRxiv : the preprint server for biology · 2023Article
- Non-canonical pathways in the pathophysiology and therapeutics of bipolar disorder.Frontiers in neuroscience · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveMitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy.
methodsTwenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 ± 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome.
resultsSubjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels.
conclusionsThis is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions.
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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.