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 M. Simonsick, Richard G. Spencer, L. Ferrucci

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)963-971
Number of pages9
JournalAmerican Journal of Geriatric Psychiatry
Issue number9
StatePublished - Sep 2019


  • Mitochondrial function
  • aging
  • depression
  • fatigue
  • longitudinal

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


Dive into the research topics of 'Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life'. Together they form a unique fingerprint.

Cite this