Vanessa F Gonçalves1, Ana Paula Mendes-Silva2, Emiko Koyama2, Erica Vieira2, James L Kennedy3, Breno Diniz4. 1. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: vanessa.goncalves@camh.ca. 2. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 3. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 4. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
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.
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.
Authors: Emi Ampo; Ana Paula Mendes-Silva; Vanessa Goncalves; Jenna M Bartley; George A Kuchel; Breno S Diniz Journal: Am J Geriatr Psychiatry Date: 2021-07-29 Impact factor: 4.105