ArticleMolecular psychiatry2016
Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
48 citing papers in PubMed, 110 citations in OpenAlex.
- Enhanced axonal mitochondrial motility and neural activity-induced energy deficits destabilize synaptic transmission in models of bipolar disorder.Nature communications · 2026Article
- Integrated multi-omics analysis of gut microbiome and serum metabolome in unipolar and bipolar depression.European archives of psychiatry and clinical neuroscience · 2026Article
- Mitochondrial Gene Signature Reveals Novel Diagnostic Biomarkers for Autism Spectrum Disorder.Molecular neurobiology · 2026Article
- Increased Cerebrospinal Fluid Lactate Levels in Schizophrenia and Major Depressive Disorder: NCNP Biobank Study in Japan.Neuropsychopharmacology reports · 2026Article
- Bioenergetic biomarkers as predictive indicators and their relationship with cognitive function in newly diagnosed, drug-naïve patients with bipolar disorder.Translational psychiatry · 2025Article
- Pilot study of a ketogenic diet in bipolar disorder: a process evaluation.BMC psychiatry · 2025Article
- Psychoneuroimmunology of Mood Disorders.Methods in molecular biology (Clifton, N.J.) · 2025Review
- The St. Göran Project: A Multipronged Strategy for Longitudinal Studies for Bipolar Disorders.Neuropsychobiology · 2025Article
- Review
- A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology.Signal transduction and targeted therapy · 2024Article
- Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study.Discover mental health · 2024Article
- Mitochondrial health index correlates with plasma circulating cell-free mitochondrial DNA in bipolar disorder.Molecular psychiatry · 2023Article
- Pilot study of a ketogenic diet in bipolar disorder.BJPsych open · 2023Article
- Mitochondria dysfunction and bipolar disorder: From pathology to therapy.IBRO neuroscience reports · 2023Article
- Article
- Metabolomic Profiling of Bipolar Disorder byMetabolites · 2023Article
- Article
- Integrated analyses of brain and platelet omics reveal their common altered and driven molecules in Alzheimer's disease.MedComm · 2022Article
- Alterations of the Intestinal Permeability are Reflected by Changes in the Urine Metabolome of Young Autistic Children: Preliminary Results.Metabolites · 2022Article
- Metabolomics analysis of cerebrospinal fluid suggests citric acid cycle aberrations in bipolar disorder.Neuroscience applied · 2022Article
Corrections and comments
- Commented on by
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD.
Indexed as
Identifiers
What OpenQuestion holds
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.