Highlights
- •What is the primary question addressed in this study?
- ○Recent studies have implicated non-normative age-related processes in the pathogenesis of late life depression. The primary question tested in this study is whether dysfunction in one such age-related process, skeletal muscle mitochondrial function, is associated with and increases risk for late life depression.
- •What is the main finding of this study?
- ○The main finding of the study is that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up.
- •What is the meaning of the finding?
- ○This study provides preliminary support for the hypothesis that mitochondrial dysfunction may be a potential key pathophysiological mechanism in adults with late life depression.
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.
Key Words
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References
- Clinical and neuroradiologic features associated with chronicity in late-life depression.Am J Geriatr Psychiatry. 1999; 7: 309-316
- Biological age, not chronological age, is associated with late life depression.J Gerontol A Biol Sci Med Sci. 2018; 73: 1370-1376
- Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
- Skeletal muscle mitochondrial function and fatigability in older adults.J Gerontol A Biol Sci Med Sci. 2015; 70: 1379-1385
- Respirometric profiling of muscle mitochondria and blood cells are associated with differences in gait speed among community-dwelling older adults.J Gerontol A Biol Sci Med Sci. 2015; 70: 1394-1399
- Reconsidering the role of mitochondria in aging.J Gerontol A Biol Sci Med Sci. 2015; 70: 1334-1342
- Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults.J Gerontol A Biol Sci Med Sci. 2013; 68: 447-455
- Serum lactate as a novel potential biomarker in multiple sclerosis.Biochim Biophys Acta. 2014; 1842: 1137-1143
- Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients.J Affect Disord. 2003; 76: 55-68
- Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression.Transl Psychiatry. 2014; 4: e397
- Parkinson's disease and brain mitochondrial dysfunction: a functional phosphorus magnetic resonance spectroscopy study.J Cereb Blood Flow Metab. 2006; 26: 283-290
- 31P Magnetic resonance spectroscopy assessment of muscle bioenergetics as a predictor of gait speed in the Baltimore Longitudinal Study of Aging.J Gerontol A Biol Sci Med Sci. 2016; 71: 1638-1645
- The relationship between mitochondrial function and walking performance in older adults with a wide range of physical function.Exp Gerontol. 2016; 81: 1-7
- Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/medical magnetic resonance spectroscopy signals.Comput Biol Med. 2001; 31: 269-286
- Java-based graphical user interface for the MRUI quantitation package.MAGMA. 2001; 12: 141-152
- Time-domain quantification of series of biomedical magnetic resonance spectroscopy signals.J Magn Reson. 1999; 140: 120-130
- Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles.J Appl Physiol. 1993; 75: 813-819
- Assessing depressive symptoms in five psychiatric populations: a validation study.Am J Epidemiol. 1977; 106: 203-214
- Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community-based sample of older subjects in the Netherlands.Psychol Med. 1997; 27: 231-235
- The Pittsburgh Fatigability scale for older adults: development and validation.J Am Geriatr Soc. 2015; 63: 130-135
- Fatigue and fatigability in older adults.PM R. 2010; 2: 406-413
- A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.J Gerontol. 1994; 49: M85-M94
- “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician.J Psychiatr Res. 1975; 12: 189-198
- Bias reduction of maximum likelihood estimates.Biometrika. 1993; 80: 27-38
- Inflammation, depression, and slow gait: a high mortality phenotype in later life.J Gerontol A Biol Sci Med Sci. 2016; 71: 221-227
- The depressed frail phenotype: the clinical manifestation of increased biological aging.Am J Geriatr Psychiatry. 2016; 24: 1084-1094
- Biological aging and the future of geriatric psychiatry.J Gerontol A Biol Sci Med Sci. 2017; 72: 343-352
- Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress.Proc Natl Acad Sci U S A. 2015; 112: E6614-E6623
- Mitochondrial etiology of neuropsychiatric disorders.Biol Psychiatry. 2018; 83: 722-730
- Effects of exercise on mitochondrial content and function in aging human skeletal muscle.J Gerontol A Biol Sci Med Sci. 2006; 61: 534-540
- Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions.Brain. 2006; 129: 3391-3401
- Inflammation, mitochondria, and the inhibition of adult neurogenesis.J Neurosci Res. 2011; 89: 1989-1996
- Mitochondrial abnormalities in Alzheimer's disease: possible targets for therapeutic intervention.Adv Pharmacol. 2012; 64: 83-126
- Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation.Front Cell Neurosci. 2015; 9: 476
- The molecular intersection between senescence and major depression in the elderly.Am J Geriatr Psychiatry. 2018; 26: 1097-1105
- Test-retest reliability of brain mitochondrial cytochrome-c-oxidase assessed by functional near-infrared spectroscopy.J Biomed Opt. 2018; 23: 1-9
Article info
Publication history
Published online: May 16, 2019
Accepted:
March 29,
2019
Received in revised form:
March 29,
2019
Received:
November 26,
2018
Identification
Copyright
© 2019 Published by Elsevier Inc. on behalf of American Association for Geriatric Psychiatry.
