Patrick J Brown1, Nicholas Brennan2, Adam Ciarleglio3, Chen Chen4, Carolina Montes Garcia5, Stephanie Gomez5, Steven P Roose6, Bret R Rutherford6, Eleanor M Simonsick2, Richard G Spencer7, Luigi Ferrucci2. 1. Neurobiology and Therapeutics of Aging Division (PJB, SPR, BRR), Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York. Electronic address: pb2410@cumc.columbia.edu. 2. Intramural Research Program (NB, EMS, LF), National Institute on Aging, Bethesda, Maryland. 3. Milken Institute School of Public Health (AC), George Washington University, Washington DC. 4. Mailman School of Public Health (CC), Columbia University, New York State Psychiatric Institute, New York. 5. New York State Psychiatric Institute (CMG, SG), New York, NY. 6. Neurobiology and Therapeutics of Aging Division (PJB, SPR, BRR), Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York. 7. Laboratory of Clinical Investigation (RGS), National Institute on Aging.
Abstract
OBJECTIVE: Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. METHODS: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t = -0.553, df = 542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATPmax]; t = 0.804, df = 553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D ≥16) at follow-up (ΔATPmax: odds ratio = 2.63, χ2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ2 = 5.79, df =1; p = 0.016). CONCLUSION: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a potential key pathophysiological mechanism in adults with LLD.
OBJECTIVE:Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. METHODS: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t = -0.553, df = 542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATPmax]; t = 0.804, df = 553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D ≥16) at follow-up (ΔATPmax: odds ratio = 2.63, χ2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ2 = 5.79, df =1; p = 0.016). CONCLUSION: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a potential key pathophysiological mechanism in adults with LLD.
Authors: Patrick J Brown; Steven P Roose; Jun Zhang; Melanie Wall; Bret R Rutherford; Hilsa N Ayonayon; Meryl A Butters; Tamara Harris; Anne B Newman; Suzanne Satterfield; Eleanor M Simonsick; Kristine Yaffe Journal: J Gerontol A Biol Sci Med Sci Date: 2015-09-20 Impact factor: 6.053
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