ArticlePsychopharmacology2015
Lithium increases leukocyte mitochondrial complex I activity in bipolar disorder during depressive episodes.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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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
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Beyond the Mind-Serum Trace Element Levels in Schizophrenic Patients: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Pooled it
- Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.Journal of clinical psychopharmacology · 2017Trial
- Lifetime adversity exposure, mood symptoms, and immune mitochondrial bioenergetics.medRxiv : the preprint server for health sciences · 2026Article
- Aerobic glycolysis in Schizophrenia: Developmental rescue or energetic breakdown?Molecular psychiatry · 2026Review
- Lithium Therapeutic Functions: An Update on Pharmacokinetics, Pathophysiological Mechanisms of Action, Toxicity, and Side Effects.Molecular neurobiology · 2026Review
- Premature aging in serious mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Lithium-induced neuroprotection in bipolar disorder: Translational insights into cytoskeletal and proteomic mechanisms.IBRO neuroscience reports · 2025Review
- Differential effects of lithium on metabolic dysfunctions in astrocytes derived from bipolar disorder patients.Molecular psychiatry · 2025Article
- The Mechanisms of Lithium Action: The Old and New Findings.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Psychoneuroimmunology of Mood Disorders.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Protective effects of psychiatric medications against COVID-19 mortality before vaccines.PloS one · 2025Article
- The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality.GeroScience · 2024Observational
- New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.Pharmacological reviews · 2024Review
- Mitochondria dysfunction and bipolar disorder: From pathology to therapy.IBRO neuroscience reports · 2023Article
- Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania.Molecular psychiatry · 2023Article
- Mitochondrial signal transduction.Cell metabolism · 2022Review
- Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress-Induced Damage in Patients with Bipolar Disorder.International journal of molecular sciences · 2022Review
- Lithium increases mitochondrial respiration in iPSC-derived neural precursor cells from lithium responders.Molecular psychiatry · 2021Article
- Mini-review: The anti-aging effects of lithium in bipolar disorder.Neuroscience letters · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleDifferent lines of evidence suggest that mitochondrial dysfunction may be implicated in bipolar disorder (BD) pathophysiology. Mitochondrial electron transport chain (ETC) is a key target to evaluate mitochondrial function, but its activity has never been assessed in unmedicated BD or during mood episodes. Also, lithium has been shown to increase ETC gene expression/activity in preclinical models and in postmortem brains of BD subjects, but to date, no study has evaluated lithium's direct effects on ETC activity in vivo.
objectivesThis study aims to evaluate leukocyte ETC complexes I-IV activities in acute depressive episode in BD (compared to controls) and the effect of lithium treatment on ETC activity.
methodsSubjects with short-term BD during a depressive episode (n=25) were treated for 6 weeks with lithium. Leukocytes were collected at baseline and endpoint and mitochondrial ETC complexes I-IV activities were evaluated and compared to age-matched healthy controls (n=24).
resultsLithium significantly increased mitochondrial complex I activity from baseline to endpoint (p=0.02), with no changes in other complexes after 6 weeks. Also, plasma lithium levels were significantly correlated to mitochondrial complex I activity after treatment (p=0.003). Mitochondrial complexes I-IV activities did not differ during depressive episodes in BD compared to healthy controls.
conclusionsOur findings demonstrate for the first time an increase in mitochondrial ETC complex I activity in vivo after lithium treatment in BD, which was positively associated with plasma lithium levels. Further studies are warranted to clarify the potential role of this target in neuroprotection-related drug development.
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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.