Mitochondrial dysfunction, a new marker warning of neuropsychiatric disorder risk: evidence from genetics and epidemiology

Chung JK, Lee SY, Park M, Joo EJ, Kim SA. Investigation of mitochondrial DNA copy number in patients with major depressive disorder. Psychiatry Res. 2019;282:112616.

Article  CAS  PubMed  Google Scholar 

Elbatarny M, Lu YT, Hu M, Coles J, Mital S, Ross-White A, et al. Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic review. EBioMedicine. 2025;118:105839.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tharayil SP, Shukla P. Connecting the dots: mitochondrial dysfunction, PCOS, and insulin resistance-insights and therapeutic advances. Int J Mol Sci. 2025;26(13):6233. https://doi.org/10.3390/ijms26136233.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wei P, Zhang X, Yan C, Sun S, Chen Z, Lin F. Mitochondrial dysfunction and aging: multidimensional mechanisms and therapeutic strategies. Biogerontology. 2025;26:142.

Article  PubMed  PubMed Central  Google Scholar 

Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–65.

Article  CAS  PubMed  Google Scholar 

Liu Z, Fu Q, Shao Y, Duan X. The role of mitochondrial DNA copy number in autoimmune disease: a bidirectional two sample Mendelian randomization study. Front Immunol. 2024;15:1409969.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Castellani CA, Longchamps RJ, Sun J, Guallar E, Arking DE. Thinking outside the nucleus: mitochondrial DNA copy number in health and disease. Mitochondrion. 2020;53:214–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harerimana NV, Paliwali D, Romero-Molina C, Bennett DA, Pa J, Goate A, et al. The role of mitochondrial genome abundance in Alzheimer’s disease. Alzheimers Dement. 2023;19:2069–83.

Article  CAS  PubMed  Google Scholar 

Ashar FN, Zhang Y, Longchamps RJ, Lane J, Moes A, Grove ML, et al. Association of mitochondrial DNA copy number with cardiovascular disease. JAMA Cardiol. 2017;2:1247–55.

Article  PubMed  PubMed Central  Google Scholar 

Qin P, Qin T, Liang L, Li X, Jiang B, Wang X, et al. The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample Mendelian randomization study. Cardiovasc Diabetol. 2024;23:45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu X, Longchamps RJ, Wiggins KL, Raffield LM, Bielak LF, Zhao W, et al. Association of mitochondrial DNA copy number with cardiometabolic diseases. Cell Genom. 2021;1(1):514–21. https://doi.org/10.1016/j.xgen.2021.100006.

Article  CAS  Google Scholar 

Green R, Allen LH, Bjørke-Monsen A-L, Brito A, Guéant J-L, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:1–20.

Google Scholar 

Stepien KM, Heaton R, Rankin S, Murphy A, Bentley J, Sexton D, et al. Evidence of oxidative stress and secondary mitochondrial dysfunction in metabolic and non-metabolic disorders. J Clin Med. 2017;6(7):71. https://doi.org/10.3390/jcm6070071.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chandler RJ, Zerfas PM, Shanske S, Sloan J, Hoffmann V, DiMauro S, et al. Mitochondrial dysfunction in mut methylmalonic acidemia. FASEB J. 2009;23:1252–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Solmi M, Radua J, Olivola M, Croce E, Soardo L, Salazar de Pablo G, Il Shin J, Kirkbride JB, Jones P, Kim JH, et al. Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies. Mol Psychiatry. 2022;27:281–95.

Article  CAS  PubMed  Google Scholar 

Pan G, Fu Q, Xu Y, Jiang L. Evidence for a causal link between lipoprotein (a) and mental disorders: a retrospective and Mendelian randomization study. J Affect Disord. 2025;374:397–407. https://doi.org/10.1016/j.jad.2025.01.038.

Article  CAS  PubMed  Google Scholar 

Krystal JH, State MW. Psychiatric disorders: diagnosis to therapy. Cell. 2014;157:201–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Area-Gomez E, Guardia-Laguarta C, Schon EA, Przedborski S. Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas. J Clin Invest. 2019;129:34–45.

Article  PubMed  PubMed Central  Google Scholar 

Shivakumar V, Rajasekaran A, Subbanna M, Kalmady SV, Venugopal D, Agrawal R, et al. Leukocyte mitochondrial DNA copy number in schizophrenia. Asian J Psychiatr. 2020;53:102193.

Article  PubMed  Google Scholar 

Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19:609–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kausar S, Wang F, Cui H. The role of mitochondria in reactive oxygen species generation and its implications for neurodegenerative diseases. Cells. 2018. https://doi.org/10.3390/cells7120274.

Article  PubMed  PubMed Central  Google Scholar 

Fu Q, Yu Q, Luo H, Liu Z, Ma X, Wang H, et al. Protective effects of Wogonin in the treatment of central nervous system and degenerative diseases. Brain Res Bull. 2025;221:111202. https://doi.org/10.1016/j.brainresbull.2025.111202

Article  CAS  PubMed  Google Scholar 

Al-Kafaji G, Jahrami HA, Alwehaidah MS, Alshammari Y, Husni M. Mitochondrial DNA copy number in autism spectrum disorder and attention deficit hyperactivity disorder: a systematic review and meta-analysis. Front Psychiatry. 2023;14:1196035.

Article  PubMed  PubMed Central  Google Scholar 

Cai N, Chang S, Li Y, Li Q, Hu J, Liang J, et al. Molecular signatures of major depression. Curr Biol. 2015;25:1146–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chang CC, Jou SH, Lin TT, Lai TJ, Liu CS. Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder. PLoS ONE. 2015;10:e0125855.

Article  PubMed  PubMed Central  Google Scholar 

Lindqvist D, Wolkowitz OM, Picard M, Ohlsson L, Bersani FS, Fernström J, Westrin Å, Hough CM, Lin J, Reus VI, et al. Circulating cell-free mitochondrial DNA, but not leukocyte mitochondrial DNA copy number, is elevated in major depressive disorder. Neuropsychopharmacology. 2018;43:1557–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang S, Liu Y, Liu J, Tian W, Zhang X, Cai H, et al. Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress, predicts all-cause and cardiovascular mortality in the general population. Redox Biol. 2020;37:101741.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cao B, Xiao Y, Liu D. Associations of methylmalonic acid and depressive symptoms with mortality: a population-based study. Transl Psychiatry. 2024;14:297.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fu Q, Shen T, Yu Q, Jiang L, Yang R. Causal effect of gallstone disease on the risk of coronary heart disease or acute myocardial infa

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