{"doi":"10.1016/j.bpsgos.2025.100598","title":"Decreased Mitochondrial DNA Integrity and Elevated Inflammatory Markers in Late-Life Depression: A Longitudinal Study","abstract":"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.","journal":"Biological Psychiatry Global Open Science","year":2025,"id":524226,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":842641,"name":"Parvaiz Ahmad","orcid":"0000-0003-2734-4180","position":1,"is_corresponding":false},{"id":1204656,"name":"Ana Paula Costa","orcid":"0000-0002-4632-038X","position":2,"is_corresponding":false},{"id":1397742,"name":"Lloyd Balbuena","orcid":"0000-0002-3745-5426","position":3,"is_corresponding":false},{"id":327036,"name":"Yuliya S. Nikolova","orcid":"0000-0001-5144-3723","position":4,"is_corresponding":false},{"id":226868,"name":"Tarek K. Rajji","orcid":"0000-0002-8324-2560","position":5,"is_corresponding":false},{"id":1397743,"name":"James Kennedy","orcid":"0000-0003-2760-8318","position":6,"is_corresponding":false},{"id":436076,"name":"Érica Leandro Marciano Vieira","orcid":"0000-0002-4147-5614","position":7,"is_corresponding":false},{"id":778493,"name":"Vanessa F. Gonçalves","orcid":"0000-0001-5619-8755","position":8,"is_corresponding":false},{"id":380406,"name":"Breno S. Diniz","orcid":"0000-0003-0653-1905","position":9,"is_corresponding":false},{"id":812405,"name":"Ana Paula Mendes‐Silva","orcid":"0000-0002-0636-7239","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"41069684","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}