Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life

Patrick J. Brown, Nicholas Brennan, Adam Ciarleglio, Chen Chen, Carolina Montes Garcia, Stephanie Gomez, Steven P. Roose, Bret R. Rutherford, Eleanor Marie Simonsick, Richard G. Spencer, Luigi Ferrucci

Research output: Contribution to journalArticle

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 [ATP max ]; 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 (ΔATP max : odds ratio = 2.63, χ 2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ 2 = 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.

Original languageEnglish (US)
JournalAmerican Journal of Geriatric Psychiatry
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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Skeletal Muscle
Depression
Phosphocreatine
Epidemiologic Studies
Adenosine Triphosphate
Logistic Models
Odds Ratio
Baltimore
Phosphorus
Energy Metabolism
Longitudinal Studies
Magnetic Resonance Spectroscopy
Exercise
Muscles

Keywords

  • aging
  • depression
  • fatigue
  • longitudinal
  • Mitochondrial function

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life. / Brown, Patrick J.; Brennan, Nicholas; Ciarleglio, Adam; Chen, Chen; Garcia, Carolina Montes; Gomez, Stephanie; Roose, Steven P.; Rutherford, Bret R.; Simonsick, Eleanor Marie; Spencer, Richard G.; Ferrucci, Luigi.

In: American Journal of Geriatric Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

Brown, Patrick J. ; Brennan, Nicholas ; Ciarleglio, Adam ; Chen, Chen ; Garcia, Carolina Montes ; Gomez, Stephanie ; Roose, Steven P. ; Rutherford, Bret R. ; Simonsick, Eleanor Marie ; Spencer, Richard G. ; Ferrucci, Luigi. / Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life. In: American Journal of Geriatric Psychiatry. 2019.
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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 [ATP max ]; 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 (ΔATP max : odds ratio = 2.63, χ 2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ 2 = 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.",
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AU - Brennan, Nicholas

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AU - Garcia, Carolina Montes

AU - Gomez, Stephanie

AU - Roose, Steven P.

AU - Rutherford, Bret R.

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N2 - 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 [ATP max ]; 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 (ΔATP max : odds ratio = 2.63, χ 2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ 2 = 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.

AB - 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 [ATP max ]; 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 (ΔATP max : odds ratio = 2.63, χ 2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ 2 = 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.

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