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Record W4413371468 · doi:10.1016/j.bpsgos.2025.100598

Decreased Mitochondrial DNA Integrity and Elevated Inflammatory Markers in Late-Life Depression: A Longitudinal Study

2025· article· en· W4413371468 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueBiological Psychiatry Global Open Science · 2025
Typearticle
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsUniversity of TorontoUniversity of SaskatchewanCentre for Addiction and Mental Health
FundersNational Institute of Neurological Disorders and StrokeNational Institutes of HealthCanada Research ChairsOntario Ministry of Health and Long-Term CareCentre for Addiction and Mental HealthCanada Foundation for InnovationCanadian Institutes of Health ResearchWeston Brain InstituteCentre for Addiction and Mental Health FoundationNational Alliance for Research on Schizophrenia and DepressionBrightFocus FoundationFondation Brain CanadaNational Institute of Mental HealthUniversity of SaskatchewanOntario Ministry of Research and InnovationNational Institute of Mental Health and NeurosciencesBrain and Behavior Research Foundation
KeywordsMitochondrial DNADepression (economics)Late life depressionBiologyGeneticsMedicineEndocrinologyGene

Abstract

fetched live from OpenAlex

Background Late-life depression (LLD) is a prevalent and severe mental disorder. The biological mechanisms underlying LLD are not fully understood, but increasing evidence suggests that mitochondria play a significant role. Impaired mitochondrial function leads to excessive production of reactive oxygen species and the release of circulating cell-free mitochondrial DNA (ccf-mtDNA). The ccf-mtDNA activates the toll-like receptor system, triggering a systemic pro-inflammatory response. However, there is a limited understanding of the impact of ccf-mtDNA integrity, such as deletions, on to LLD pathological conditions. Methods We included 90 elderly individuals (50 LLD, 40 non-depressed control (NDC)), with a subset of individuals followed up at 30 months (13 LLD, 13 NDC). Plasma was separated from blood, and DNA was extracted. Mitochondrial genes MT-ND2 and MT-ND4 were targeted to evaluate ccf-mtDNA levels and deletion using real-time qPCR. Plasma interleukins 1 β , 5, and 6 were quantified via multiplex immunoassay. Results Our findings indicate that LLD is linked to increased ccf-mtDNA instability at baseline (deletion: F (88,1) =7.105, p=0.009; levels: F (88,1) =6.885, p=0.01), which were associated with more severe depressive symptoms and greater medical comorbidity burden. Longitudinal analysis revealed significant effects of diagnosis and time on the ccf-mtDNA levels and deletion rate. Additionally, higher deletion rates at the baseline predicted IL-5 and IL-6 levels at 30 months (p adj =0.13, p adj =0.12, respectively). Conclusions Increased ccf-mtDNA instability may heighten vulnerability to emotional dysregulation and medical burden in individuals with LLD. Further research is needed to validate our findings and elucidate the mechanisms connecting mitochondrial instability and inflammation in LLD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score0.781

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0020.002
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.049
GPT teacher head0.346
Teacher spread0.297 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it