The association of mitochondrial DNA copy number with incident mental disorders in women: A population-based follow-up study

Background: Available evidence suggests that mitochondrial DNA copy number (mtDNA-CN) may differ among patients with mental disorders compared to the general population. However, whether mtDNA-CN is independently associated with the subsequent incidence of mental disorders remains unclear. Material and methods: We used droplet digital PCR to measure the absolute mtDNA-CN in DNA samples obtained from a population-based follow-up study, which included a total of 2354 middle-aged women (52–63 years) who were free of mental disorders at baseline. After 17 years (median) of follow-up, 727 participants were diagnosed with mental disorders. Results: In the univariate Cox regression, lower baseline mtDNA-CN (mtDNA-CN < 117) was associated with a higher risk of mental disorders (HR = 1.16, p = 0.047). In addition, smoking, marital status and sleeping quality were associated with both mtDNA-CN and mental disorders. After adjusting for these variables, the association between mtDNA-CN and mental disorders decreased and became non-significant (HR = 1.07, p = 0.36). Stratification of data according to the subtype of mental disorders, showed that low mtDNA-CN was associated with a higher risk of alcohol or drug use disorders (HR = 1.82, p = 0.045 after adjusting). Conclusion: In the present study, we could not find any independent association between mtDNA-CN blood and the most common mental disorders in a population-based follow-up study of Swedish women, except for alcohol and drug use disorders. The use of blood mtDNA-CN as a biomarker of mental disorders, in addition to other risk factors, needs to be further examined in future studies.