ArticleInternational journal of bipolar disorders2024
Pilot study of circulating cell-free mitochondrial DNA in relation to brain structure in youth bipolar disorder.
Article in International journal of bipolar disorders, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Circulating Cell-Free DNA in Psychiatric Disorders: Current Evidence, Inflammation-Based Stratification, and Future Perspectives.International journal of molecular sciences · 2026Review
- Nanotechnology-Enhanced MicroRNAs for Improved Diagnosis and Treatment of Major Depressive Disorder: A Comprehensive Review.Molecular neurobiology · 2025Review
- iPSC-derived cerebral organoids reveal mitochondrial, inflammatory and neuronal vulnerabilities in bipolar disorder.Translational psychiatry · 2025Article
- Cell-free mitochondrial DNA as a pro-inflammatory agent in blood circulation: mechanisms, therapeutic implications, and clinical challenges in immune dysregulation.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundMitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group.
methodsParticipants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13-20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume.
resultsThere was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (β = 0.32 p < 0.001) and PFC volume (β = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: β = 0.39 p = 0.02; CG: β = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (β = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG.
conclusionsContrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted.
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