Increased levels of circulating cell-free mtDNA in plasma of late life depression subjects

Abstract Background Oxidative stress (OS) has been implicated in the pathophysiology of late-life depression (LLD). Mitochondria are the primary source of oxidative stress and can be significantly damaged with increased OS. Circulating cell-free mtDNA (ccf-mtDNA) is a marker of cellular stress and mitochondria damage triggered by oxidative stress. Methods: We evaluated the plasma levels of ccf-mtDNA in between 32 LLD and 21 never-depressed participants. We also investigated the association between ccf-mtDNA and the severity of depressive episodes and cognition performance. Results: We found a higher ccf-mtDNA level in LLD cases compared with controls (t=-2.91, p=0.005). Also, ccf-mtDNA was significantly correlated with the severity of depression (r=0.42, p=0.001). There was no significant correlation between ccf-mtDNA and measures of cognitive decline. Limitations: The small sample size and cross-sectional design were the main limitations of this study. Conclusion: Our results suggest that LLD is associated with elevated mitochondrial damage and cellular stress. If validated, the measurement of ccf-mtDNA in LLD can guide the development of novel treatments focused on cytoprotection and reduction of mitochondrial dysfunction for this condition.