Circulating cell-free mitochondrial DNA in brain health and disease: A systematic review and meta-analysis
Bibliographic record
Abstract
Circulating cell-free mitochondrial DNA (ccf-mtDNA) are detectable fragments of mtDNA released from the cell as a result of mitochondrial dysfunction or apoptosis. The brain is one of the most energy demanding organs in the human body, and many neuropsychiatric and non-psychiatric neurological diseases have mitochondrial dysfunction associated with disease pathophysiology. Thus, we aimed to assess ccf-mtDNA as a potential biomarker for brain diseases. We conducted a systematic review and meta-analyses of studies that examined peripheral and/or cerebrospinal fluid (CSF) ccf-mtDNA relevant to neuropsychiatric conditions, which we define as disorders of affect, behaviour and mood, and non-psychiatric neurological diseases, which consist of neurological diseases not related to psychiatry including neurodegenerative diseases. The results of the sensitivity analysis investigating the levels of peripheral ccf-mtDNA in neuropsychiatric studies showed no significant difference between cases and controls (Z = 1.57; p = 0.12), whereas the results of the sensitivity analysis investigating the levels of CSF ccf-mtDNA in non-psychiatric neurological diseases showed a decreasing trend in cases compared with controls (Z = 2.32; p = 0.02). Interestingly, the results indicate an overall mitochondrial stress associated mainly with non-psychiatric neurological diseases. Our study supports the involvement of mitochondrial stress, here defined as ccf-mtDNA, in brain diseases and encourage further investigation of ccf-mtDNA among patients with brain diseases.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.012 | 0.018 |
| Bibliometrics | 0.005 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".