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

Am J Geriatr Psychiatry. 2019 Sep;27(9):963-971. doi: 10.1016/j.jagp.2019.03.022. Epub 2019 Apr 6.


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.

Keywords: Mitochondrial function; aging; depression; fatigue; longitudinal.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aging / metabolism*
  • Cross-Sectional Studies
  • Depressive Disorder / etiology*
  • Depressive Disorder / physiopathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mitochondrial Diseases / complications*
  • Mitochondrial Diseases / metabolism*
  • Muscle, Skeletal / metabolism*