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The Depressed Frail Phenotype: The Clinical Manifestation of Increased Biological Aging

Published on Nov 1, 2016in American Journal of Geriatric Psychiatry3.488
· DOI :10.1016/j.jagp.2016.06.005
Patrick J. Brown15
Estimated H-index: 15
(Columbia University),
Bret R. Rutherford20
Estimated H-index: 20
(Columbia University)
+ 5 AuthorsSteven P. Roose52
Estimated H-index: 52
(Columbia University)
Sources
Abstract
Depression in later life is a severe public health problem, associated with higher rates of mortality, suicide, and dementia. Effectiveness of treatment is limited by the failure to deconstruct the heterogeneity of the illness and because diagnostic criteria, pathophysiological models, and treatment algorithms for depression are primarily based on studies of younger adults even though symptoms of the illness and physiology of the patient change with age. Thus, understanding how aging interacts with depressive illness may elucidate endophenotypes of late-life depression with different clinical manifestations and underlying mechanisms that can then be targeted with more personalized approaches to treatment. This paper proposes a model for the critical confluence between depression and frailty, a high-risk morbidity and mortality syndrome of later life. This model hypothesizes that characteristics of frailty in adults with late life depression represent the clinical manifestation of greater biological aging and their presence in the context of a depressive illness exposes elders to deleterious trajectories. Potential common biological substrates that may result in the manifestation of the depressed frail phenotype including mitochondrial functioning, dopaminergic neurotransmission, and inflammatory processes and implications for the assessment and treatment of adults with late-life depression are discussed. As society continues to live longer, the preservation of the quality of these added years becomes paramount, and the combined impact of depression and frailty on the preservation of this quality warrants the attention of clinical researchers and physicians.
  • References (76)
  • Citations (22)
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References76
Newest
#1Matthew C. Lohman (Cornell University)H-Index: 12
#2Levent DumenciH-Index: 30
Last. Briana Mezuk (VCU: Virginia Commonwealth University)H-Index: 27
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Objectives. The study purpose is to estimate the correlation between depression and competing models of frailty, and to determine to what degree the comorbidity of these syndromes is determined by shared symptomology.
37 CitationsSource
#1Patrick J. Brown (Columbia University)H-Index: 15
#2Steven P. Roose (Columbia University)H-Index: 52
Last. Kristine Yaffe (UCSF: University of California, San Francisco)H-Index: 116
view all 12 authors...
24 CitationsSource
#1Adam J. Santanasto (University of Pittsburgh)H-Index: 7
#2Nancy W. Glynn (University of Pittsburgh)H-Index: 33
Last. A. Newman (University of Pittsburgh)H-Index: 150
view all 12 authors...
2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05). Conclusions. Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults.
34 CitationsSource
#1Daniel J. Tyrrell (Wake Forest University)H-Index: 7
#2Manish S. Bharadwaj (Wake Forest University)H-Index: 14
Last. Anthony J.A. Molina (Wake Forest University)H-Index: 19
view all 6 authors...
Background. Gait speed pro vides an integrated measure of physical ability that is predictive of morbidity, disability, and mortality in older adults. Energy demands associated with walking suggest that mitochondrial bioenergetics may play a role in gait speed. Here, we examined the relationship between gait speed and skeletal muscle mitochondrial bioenergetics, and further evaluated whether blood-based bioenergetic profiling might have similar associations with gait speed. Methods. P articipant...
38 CitationsSource
#1Cristina Buigues (University of Valencia)H-Index: 5
#2Celia Padilla-Sánchez (University of Valencia)H-Index: 1
Last. Omar Cauli (University of Valencia)H-Index: 30
view all 6 authors...
52 CitationsSource
#1Daniel Lindqvist (UCSF: University of California, San Francisco)H-Index: 20
#2Elissa S. Epel (UCSF: University of California, San Francisco)H-Index: 71
Last. Owen M. Wolkowitz (UCSF: University of California, San Francisco)H-Index: 61
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Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a ...
121 CitationsSource
Background: Mitochondrial dysfunction has long been considered a major contributor to aging and age-related diseases. Harman ’s Mitochondrial Free Radical Theory of Aging postulated that somatic mitochondrial DNA mutations that accumulate over the life span cause excessive production of reactive oxygen species that damage macromolecules and impair cell and tissue function. Indeed, studies have shown that maximal oxidative capacity declines with age while reactive oxygen species production increa...
82 CitationsSource
#1Lesley M. Arnold (University of Cincinnati Academic Health Center)H-Index: 50
#2Thomas J. Blom (University of Cincinnati Academic Health Center)H-Index: 14
Last. Alicia Heller (University of Cincinnati Academic Health Center)H-Index: 1
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Objective To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome. Methods A 12-week, randomized, double-blind study was designed to compare duloxetine 60–120mg/d ( n = 30) with placebo ( n = 30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome. The primary outcome measure was the Multidimensional Fatigue Inventory general fatigue subscale (range: 4–20, with higher scores indicating greater fatigue). Secondary measures were the ...
6 CitationsSource
#1Na Cai (Wellcome Trust Centre for Human Genetics)H-Index: 10
#2Simon Chang (CGU: Chang Gung University)H-Index: 2
Last. Jonathan Flint (ECNU: East China Normal University)H-Index: 12
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Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2....
109 CitationsSource
#1Gerwyn Morris (Cardiff University)H-Index: 21
#2Michael BerkH-Index: 93
Background Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome.
102 CitationsSource
Cited By22
Newest
#1Mu-N Liu (NYMU: National Yang-Ming University)H-Index: 1
#2Heng-Liang YehH-Index: 8
Last. Chi-Ieong LauH-Index: 7
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OBJECTIVE: Late-life depression (LLD) is a severe public health problem. Given that pharmacological treatments for LLD are limited by their side effects, development of efficient and tolerable nonpharmacological treatment for LLD is urgently required. This study investigated whether high-frequency external muscle stimulation could reduce depressive symptoms in LLD. METHODS: Twenty-two older male veterans with major depression were recruited and randomized into a treatment (n = 9) or sham control...
Source
#1Patrick J. Brown (Columbia University)H-Index: 15
#2Steven P. Roose (Columbia University)H-Index: 52
Last. Bret R. Rutherford (Columbia University)H-Index: 20
view all 11 authors...
Abstract Objectives To investigate the rates of frailty and frailty characteristics and examine the clinical and neuropsychological correlates of frailty in adults with late life depression (LLD). Methods Data were used from the evaluation of 134 individuals over the age of 60 years (45 men, 89 women) with a depressive diagnosis who enrolled in studies for the treatment of their depression. Depression, neuropsychological functioning, white matter hyperintensity (WMH) burden via magnetic resonanc...
Source
INTRODUCTION: Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality, and utilization in older adults. Depression and frailty often coexist, suggesting a bidirectional relationship that may increase the effects of each individual condition on clinical outcomes and health-care utilization in older adults. OBJECTIVE: To determine the effects of concurrent frailty and depression on all-cause hospitalizations. METHODS/DESIGN: Prospective cohort study, conducted at ...
Source
#1Ruth T. MorinH-Index: 3
#2Philip S. Insel (Lund University)H-Index: 27
Last. Scott Mackin (UCSF: University of California, San Francisco)H-Index: 22
view all 5 authors...
ABSTRACTObjectives: Assess the relationship of cognitive impairment to disability, accounting for depression severity and frailty, among older adults with late-life depression (LLD).Methods: Data w...
Source
#1Na Zhang (Fudan University)
#2Guo-Ping ShiH-Index: 59
Last. Xiaofeng Wang (Fudan University)H-Index: 19
view all 12 authors...
Background and aims This study aimed at investigating whether depression symptoms are associated with prevalent and incident physical frailty in Chinese older population.
Source
Although there is substantial evidence about the association between frailty and mental illnesses in older people, there is currently little evidence about how this is integrated into psychiatric clinical practice. The purpose of this paper is to explore the attitudes of a sample of psychiatrists in the UK about the concept and assessment of frailty in their clinical practice.,This research used a qualitative approach with semi-structured interviews. Interview schedules and transcripts were anal...
1 CitationsSource
#1Matthew Prina ('KCL': King's College London)H-Index: 12
#2Brendon Stubbs (South London and Maudsley NHS Foundation Trust)H-Index: 48
Last. Yu-Tzu Wu ('KCL': King's College London)H-Index: 15
view all 8 authors...
ABSTRACT Objective Frailty and depression are highly comorbid conditions, but the casual direction is unclear and has not been explored in low- and middle-income countries. The aim of this study was to investigate the potential impact of depression on incident frailty in older people living in Latin America. Methods This study was based on a population-based cohort of 12,844 people aged 65 or older from six Latin American countries (Cuba, Dominican Republic, Mexico, Venezuela, Puerto Rico, and P...
1 CitationsSource
#1Patrick J. Brown (Columbia University)H-Index: 15
#2Nicholas Brennan (NIH: National Institutes of Health)H-Index: 1
Last. Luigi Ferruci (NIH: National Institutes of Health)H-Index: 161
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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 poste...
Source
#1Breno S. Diniz (U of T: University of Toronto)H-Index: 7
#2Charles F. Reynolds (University of Pittsburgh)H-Index: 107
Last. Brenda W.J.H. Penninx (PHRI: Public Health Research Institute)H-Index: 134
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Recent evidence suggests a significant overlap in biological changes between major depression and aging across the lifespan. We aim to evaluate the impact of a major depressive episode on the Senescence-Associated Secretory Phenotype (SASP) index, a dynamic secretory molecular pattern indicative of cellular senescence. We also tested the potential moderators of the association between major depression and the SASP index. We included 1165 young and middle-aged adults (527 with a current major dep...
Source
#1Bret R. Rutherford (Columbia University)H-Index: 20
#2Mark Slifstein (SBU: Stony Brook University)H-Index: 52
Last. Steven P. Roose (Columbia University)H-Index: 52
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Abstract Background A high-risk subgroup of older patients with depression has slowed processing and gait speeds. This study examined whether carbidopa/levodopa (L-DOPA) monotherapy increased dopamine availability, increased processing/gait speed, and relieved depressive symptoms. Methods Adult outpatients with depression >59 years old underwent baseline [11C]raclopride positron emission tomography followed by open L-DOPA for 3 weeks (1 week each of 150 mg, 300 mg, and 450 mg). Generalized estim...
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