Using Circulating Cell-free mtDNA to Examine the Synergetic Effects of Major Depressive Disorder and Frailty

Abstract

<h3>Introduction</h3> Major depressive disorder (MDD) and frailty are common disorders in elderly populations. These conditions are associated with a higher rate of negative health outcomes and comorbidity. In previous studies, the measurement of circulating cell-free mtDNA (ccf-mtDNA) has been used as biomarkers for cellular stress from increased oxidative stress. No study has yet examined if there are synergistic effects of MDD and frailty in older adults through ccf-mtDNA levels. We hypothesized that individuals diagnosed with both frailty and MDD will have higher ccf-mtDNA levels in comparison to individuals with those conditions in isolation. <h3>Methods</h3> Fifty-three older adults (21 with MDD and 32 controls who were never-depressed) were included in this analysis. Pre-Frail/Frail status was determined by the FRAIL scale. Plasma samples were collected from peripheral blood collections through venipuncture in EDTA tubes. The DNA was extracted from the plasma samples using the QIAmp 96 DNA Blood Kit. The ccf-mtDNA was quantified by RT-PCR. <h3>Results</h3> There were 5 subjects classified as never-depressed and pre-frail/frail. In addition, 23 subjects were identified as depressed and pre-frail/frail. The ccf-mtDNA was significantly higher in those with MDD compared to the control group (p<.01), and in the pre-frail/frail subjects compared to robust older adults (p<.03). We found a significant interaction between MDD and frailty (p=0.03), with the group MDD+pre-frail/frail with the highest levels of ccf-mtDNA. <h3>Conclusions</h3> We found a significant interaction between MDD and frailty increasing the ccf-mtDNA. The higher levels of ccf-mtDNA could indicate worsened cellular stress and mitochondrial dysfunction among those with MDD and Frailty. Our data suggest that frailty and MDD have synergistic effects that increase co-morbidity. Future directions could include increasing the sample size to ensure the validity of the findings. <h3>Funding</h3> Funding was provided by the National Institute of Mental Health (NIMH), USA, and other Canadian funding agencies.