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Shorter Telomeres Among Individuals With Physical Disability: The Moderating Role of Perceived Stress

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Objectives: Evidence suggests that individuals with physical disability may suffer from psychological distress and accelerated cellular aging, manifested by shortened telomere length (TL), compared with healthy individuals. Studies indicate that high levels of perceived stress and depression may increase the physiological susceptibility and thus, may contribute to a short TL. However, the moderating role of perceived stress and depression within the relationship between physical disability and TL remains unknown. Methods: The participants consisted of 119 male subjects (mean age 54.36 years, range 35-70). Of them, 30 were able-bodied and 86 had a physical disability: 34 were due to Poliomyelitis (polio) and 55 were due to spinal cord injury (SCI). Blood samples for TL analysis were collected; the participants completed questionnaires and underwent disability evaluation. Results: Participants with disability had a shorter TL as well as elevated levels of perceived stress and depression compared with able-bodied controls. Both the perceived stress and depression were correlated with a shorter TL. Nonetheless, perceived stress, rather than depression, moderated the relationship between disability and TL; among participants with higher perceived stress levels, in particular, individuals with physical disability had a shorter TL than the able-bodied controls. Discussion: The present findings suggest that individuals with physical disability and who exhibit high levels of perceived stress may be particularly vulnerable for accelerated cellular aging, suggesting that perceived stress can be used as a valuable target for intervention.

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Telomeres play an important part in aging and show relationships to lifetime adversity, particularly childhood adversity. Meta-analyses demonstrate reliable associations between psychopathology (primarily depression) and shorter telomere length, but the nature of this relationship has not been fully understood. Here, we review and evaluate the evidence for impaired telomere biology as a consequence of psychopathology or as a contributing factor, and the important mediating roles of chronic psychological stress and impaired allostasis. There is evidence for a triadic relationship among stress, telomere shortening, and psychiatric disorders that is positively reinforcing and unfolds across the life course and, possibly, across generations. We review the role of genetics and biobehavioral responses that may contribute to shorter telomere length, as well as the neurobiological impact of impaired levels of telomerase. These complex interrelationships are important to elucidate because they have implications for mental and physical comorbidity and, potentially, for the prevention and treatment of depression. Expected final online publication date for the Annual Review of Clinical Psychology Volume 14 is May 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Objectives: Exposure to captivity increases the risk for multiple disturbances that may intensify during old age. In later phases of life, former-prisoners-of-war (ex-POWs) may suffer from depression as well as from accelerated aging, manifested in older subjective age and leukocyte telomere shortening. The current study assesses the link between these varied facets of increased vulnerability during old age and explores (a) the associations between subjective age and telomere length; (b) the mediating role of changes in subjective age over time within the associations between depression and telomere length. Methods: Eighty eight ex-POWs were assessed prospectively 30 (T1), 35 (T2) and 45 (T3) years after the 1973 Israeli Yom-Kippur War. Depression was assessed at T1; subjective age was assessed at T2 and T3; and telomere length and control variables were assessed at T3. Results: Older subjective age at T3 was associated with concurrent shorter telomeres, beyond the effect of chronological age. Change in subjective age between T2 and T3 mediated the relations between depression at T1 and shorter telomeres at T3 beyond the effects of control variables. Discussion: Findings suggest that the detrimental ramifications of accelerated subjective age involve premature cellular senesces, and may explain the relation between depression and accelerated aging processes among trauma victims. Hence, clinical interventions may seek to address accelerated subjective age among trauma survivors who suffer from depression.
Article
Background: Stress is a part of daily life for graduate students, including graduate nursing students. Contemporary graduate nursing students are facing unprecedented challenges to meet rigorous academic standards as they prepare for their advanced professional role to meet the demands of the nation's complex and ever-changing healthcare system. Empowering graduate nursing students to ease their perceived stress and minimize undesirable health effects may benefit their capacity to adapt and successfully manage perceived stress in their future healthcare role. Aims: To conduct a systematic review to evaluate the existing evidence with the aim of identifying evidence-based self-care interventions for coping with perceived stress. Methods: We conducted a systematic review, searching CINAHL Plus with Full Text, PsycINFO, and MEDLINE. Inclusion criteria included self-care, graduate students, perceived stress as measured by Perceived Stress Scale, quantitative analysis, conducted within the United States, English language, and peer reviewed. Two authors completed an asynchronous review of the articles, and one expert evidence-based practice mentor and one wellness expert conducted rigorous appraisal of the eight identified studies. Evidence was evaluated and synthesized, and recommendations for practice were determined. Results: Eight studies meeting the criteria for this systematic review were critically appraised. The interventions varied from a stress management course to mind-body-stress-reduction (MBSR) techniques, such as yoga, breath work, meditation, and mindfulness. All studies measured the outcome of stress with the Perceived Stress Scale. Each study demonstrated a reduction in perceived stress postintervention. Linking evidence to action: Most effective self-care MBSR interventions include (a) a didactic component, (b) a guided MBSR practice session, and (c) homework. Consideration should be given to a trained or certified MBSR instructor to teach the intervention.
Article
Background: There is evidence that stressful life events (LE) play a crucial role in the etiology of bipolar affective disorder (BD). However, primary studies, as well as narrative reviews, have provided mixed results. The present meta-analysis combined and analyzed previous data in order to address these inconsistencies. Method: Forty-two studies published in 53 records were identified by systematically searching MEDLINE, PsychINFO, and PSYCHINDEX using the terms "bipolar disorder" OR "manic-depressive" OR "bipolar affective disorder" OR "mania" AND "stress" OR "life event" OR "daily hassles" OR "goal attainment". Then, meta-analyses were conducted. Results: Individuals diagnosed with BD reported more LE before relapse when compared to euthymic phases. They also experienced more LE relative to healthy individuals and to physically ill patients. No significant difference in the number of LE was found when BD was compared to unipolar depression and schizophrenia. Limitations: When interpreting the present meta-analytic findings one should keep in mind that most included studies were retrospective and often did not specify relevant information, e.g., if the LE were chronic or acute or if the individuals were diagnosed with BD I or II. We could not entirely rule out a publication bias. Conclusion: The present meta-analyses found that individuals with BD were sensitive to LE, which corroborates recent theoretical models and psychosocial treatment approaches of BD. Childbirth, as a specific LE, affected individuals with BD more than individuals with unipolar depression. Future studies that investigate specific LE are warranted.
Article
Shortened leukocyte telomere length (LTL) is a novel biomarker for age and age-related diseases. Several epidemiological studies have examined the association between telomere length in surrogate tissues (for example, blood cells) and hypertension, and meanwhile the majority of studies reported an association some individual studies do not. We carried out a systematic review and meta-analysis to address the hypothesis that, in humans, telomere length is related with hypertension. Searches were conducted in Pubmed by September 2015 and reference lists of retrieved citations were hand searched. Eligible studies measured telomeres for both hypertensive and normotensive subjects. No restrictions were placed on sample size, publication type, age or gender. We calculated summary estimates using fixed and random effects meta-analysis. Publication bias and heterogeneity among studies were further tested. Meta-analyses from 3097 participants (1415 patients with hypertension and 1682 control subjects) showed a significant standardized mean difference between LTL in hypertensive patients and controls, either in the fixed (P<5 × 10(-6)) or the random model (P<0.005). Heterogeneity among studies was substantial (Q-statistic P-value <0.001, I(2) 97.73%). Sensitivity analysis indicated that no single study changed the standardized mean difference qualitatively (0.022> random model P-value >0.002). Egger's test for asymmetry of effect sizes (intercept±s.e.=-7.278±3.574; P=0.072) did not show evidence for strong study publication bias. Leukocyte telomeres may be shorter in hypertensive than in normotensive individuals. Larger studies controlling for confounder effects are needed to confirm these findings and further explore sources of heterogeneity.Journal of Human Hypertension advance online publication, 30 June 2016; doi:10.1038/jhh.2016.45.
Article
Lipid peroxidation due to oxidative stress (OS) may play an important role in the pathogenesis of chronic systemic inflammatory diseases such as multiple sclerosis (MS). Telomeres, repeated sequences that cap chromosome ends, undergo shortening with each cycle of cell division, resulting in cellular senescence. Research regarding telomere shortening has provided novel insight into the pathogenesis of various diseases. We hypothesized that OS damage leads to inflammatory reactions, which subsequently shortens the telomere length in MS. We enrolled 59 patients with MS, and age- and gender-matched 60 healthy controls. We divided MS subjects into three groups matched for age and gender according to the severity of disability: relatively benign course (BMS), secondary progressive MS, and primary progressive MS (PPMS). We analyzed the telomere length in peripheral blood mononuclear cells and the 8-iso-PGF2α concentration in urine, a reliable and stable marker of lipid peroxidation in vivo. The data showed significant higher levels of urinary 8-iso-PGF2α in MS subjects than in the controls. The lag-time, which represents the direct measurement of the resistance of low-density lipoprotein to oxidation, was shorter in the PPMS subjects than in the groups. Compared to that observed in the controls, the mean telomere length was significantly shorter in the PPMS group, whereas no significant telomere shortening was found between the controls and other subjects. Our data suggest that a decreased telomere length and enhanced lipid peroxidation reflects the severest stage of MS.
Article
Telomeres protect the ends of chromosomes, and short telomere length is associated with poor health and mortality. This study reports a meta-analytic investigation of the relationship between perceived stress and telomere length, including results from eight studies with a total of 1143 participants. A meta-analytic effect size of r = -0.25, p 𰀼 0.001, indicated that higher levels of perceived stress were associated with shorter telomere length. Examination of the studies for moderators of effect size identified some significant moderators, such as a difference in effect sizes between samples comprised of only women and mixed-sex samples. These results are only suggestive as they are based on a small set of studies, and funnel plot analyses indicated a publication bias. A significant relationship between more perceived stress and shorter telomere length is consistent with theoretical frameworks positing that stress induces physiological changes that result in shortened telomeres. Copyright © 2014 John Wiley & Sons, Ltd.
Article
The discovery of stress hormone receptors in the hippocampal formation has fostered research showing that the brain, including its higher cognitive centers, is the key organ of the response to stressors, both in terms of perception of what is stressful and for its ability to determine the consequences of stress for both brain and body via the neuroendocrine, autonomic, immune and metabolic systems. These systems are, in turn, responsible for either successful adaptation or pathophysiology due to the cumulative burden of adaptation to stress and maladaptive lifestyle, known as "allostatic load". The brain, itself, is also a target of stress and stress-related hormones and it undergoes structural and functional remodeling and significant changes in gene expression that are adaptive under normal circumstances but which can lead to damage when stress is excessive. The growing recognition of the adaptive plasticity and stress vulnerability of the brain itself, beginning with the hippocampus, now includes other brain regions such as the amygdala and prefrontal cortex and fear related memories, working memory, and self-regulatory behaviors. The interactions between these brain regions during the biological embedding of experiences over the life course determines whether events in the social and physical environment will lead to successful adaptation or to maladaptation and impaired mental and physical health, with implications for understanding health disparities and the impact of early life adversity and for intervention and prevention strategies.
Article
Monte Carlo computer simulations were used to investigate the performance of three χ–2 test statistics in confirmatory factor analysis (CFA). Normal theory maximum likelihood χ–2 (ML), Browne's asymptotic distribution free χ–2 (ADF), and the Satorra-Bentler rescaled χ–2 (SB) were examined under varying conditions of sample size, model specification, and multivariate distribution. For properly specified models, ML and SB showed no evidence of bias under normal distributions across all sample sizes, whereas ADF was biased at all but the largest sample sizes. ML was increasingly overestimated with increasing nonnormality, but both SB (at all sample sizes) and ADF (only at large sample sizes) showed no evidence of bias. For misspecified models, ML was again inflated with increasing nonnormality, but both SB and ADF were underestimated with increasing nonnormality. It appears that the power of the SB and ADF test statistics to detect a model misspecification is attenuated given nonnormally distributed data. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Study design: Scoping review. Objectives: To gain a better understanding of the prevalence, course and association with age of secondary health conditions in individuals with spinal cord injury (SCI). Setting: Seattle, Washington, USA. Methods: We performed searches of electronic databases for studies published from 1986-2011 that provided information regarding the prevalence, course or associations with age and duration of secondary health conditions in individuals with SCI. Results: Ninety-two studies were included. The findings indicate that: (1) individuals with SCI experience a number of secondary health conditions, many of which occur at a higher rate in those with SCI than the normative population; (2) the most common conditions or symptoms are pain, bowel and bladder regulation problems, muscle spasms, fatigue, esophageal symptom and osteoporosis; (3) a number of conditions, including cardiovascular disease, diabetes, bone mineral density loss, fatigue and respiratory complications or infections, occur with higher frequency in older individuals or those with longer SCI duration, relative to younger individuals or those with shorter SCI duration; and (4) there is a marked lack of longitudinal research examining the natural course of health conditions in individuals aging with SCI. Conclusions: The findings support the conclusion that individuals with SCI show signs of 'premature aging' in different organ systems. Longitudinal research is needed to understand when problems are most likely to emerge, and to develop and test the efficacy of interventions to prevent these health conditions and their negative impact.
Article
Research studies focusing on the psychometric properties of the Beck Depression Inventory (BDI) with psychiatric and nonpsychiatric samples were reviewed for the years 1961 through June, 1986. A meta-analysis of the BDI's internal consistency estimates yielded a mean coefficient alpha of 0.86 for psychiatric patients and 0.81 for nonpsychiatric subjects. The concurrent validitus of the BDI with respect to clinical ratings and the Hamilton Psychiatric Rating Scale for Depression (HRSD) were also high. The mean correlations of the BDI samples with clinical ratings and the HRSD were 0. 72 and 0.73, respectively, for psychiatric patients. With nonpsychiatric subjects, the mean correlations of the BDI with clinical ratings and the HRSD were 0.60 and 0.74, respectively. Recent evidence indicates that the BDI discriminates subtypes of depression and differentiates depression from anxiety.
Article
Young people with disabilities are at greater risk of having mental health problems than are their nondisabled peers. Most research about the relationship between disability and mental health has been cross-sectional and unable to identify mental health status prior to onset of disability or possible mental health pathways following disability. There is a lack of information, therefore, about what happens to young people's mental health when they become disabled. This study aimed to identify the mental health trajectories for young Australian adults after onset of self-reported disability, taking into account their predisability mental health status. Longitudinal data from waves 1 to 7 (2001 to 2007) of the survey of Household, Income and Labour Dynamics in Australia (HILDA) were analyzed using a growth mixture modeling approach. Three distinct mental health trajectories were identified for the 136 young people reporting onset of ongoing disability. The majority (64.7%) of respondents experienced positive mental health before and following onset of disability. However, a significant minority (35.3%) experienced either (a) low mental health both prior to and following onset of disability (19.1%) or (b) mental health deterioration following onset of disability (16.2%). Targeting appropriate interventions to the young people with disabilities in these 2 groups could have a significant impact on enduring mental health status.
Article
Depression is a serious comorbidity in people with disabilities; however, few studies have focused on depressive symptoms in older adults with post-polio syndrome (PPS). This study used a resilience conceptual framework that focused on patient psychosocial strengths to investigate the relationship between psychological resilience factors (e.g., acceptance, self-efficacy, personal resources, interpersonal relationships, self-rated health, spiritual growth, stress management) and depressive symptoms in a large sample (N = 630) of people older than 65 years who were diagnosed with PPS. Forty percent of the sample scored > or = 10 on the Center for Epidemiologic Studies Short Depression Scale (CES-D10), which is a higher percentage than what has been previously cited in other studies; however, 53% of the sample had good or excellent self-rated health, suggesting psychological resilience. Depression scores were regressed on seven selected resilience factors after controlling for functional limitations. Four of the seven variables accounted for 30% of the variance in depressive symptoms, with spiritual growth representing the main predictor (beta = -.26). The implications for rehabilitation nurses in developing a patient-strengths perspective in the assessment and counseling of older adults with PPS are discussed.
Article
This paper presents evidence from three samples, two of college students and one of participants in a community smoking-cessation program, for the reliability and validity of a 14-item instrument, the Perceived Stress Scale (PSS), designed to measure the degree to which situations in one's life are appraised as stressful. The PSS showed adequate reliability and, as predicted, was correlated with life-event scores, depressive and physical symptomatology, utilization of health services, social anxiety, and smoking-reduction maintenance. In all comparisons, the PSS was a better predictor of the outcome in question than were life-event scores. When compared to a depressive symptomatology scale, the PSS was found to measure a different and independently predictive construct. Additional data indicate adequate reliability and validity of a four-item version of the PSS for telephone interviews. The PSS is suggested for examining the role of nonspecific appraised stress in the etiology of disease and behavioral disorders and as an outcome measure of experienced levels of stress.
Article
This article reviews literature examining the psychological adjustment to Spinal Cord Injury (SCI) and illustrates the applicability of a Stress Appraisal and Coping model (SAC) for rehabilitation of this population. Articles concerning psychological adjustment to SCI from the previous three decades have been reviewed and critiqued. When possible the articles have been discussed in a SAC framework. The literature indicates that psychological adjustment to SCI is largely predictable from psychological variables including coping, appraisal and psychosocial resources. Recent literature has suggested psychological intervention can promote positive psychological adjustment following SCI for those individuals at risk of developing clinical levels of depression. The SAC model provides a comprehensive formulation to incorporate the heterogeneity of populations with SCI. Suggestions for future research include developing assessment and treatment regimes specifically tailored to the strengths and weaknesses of an individual as highlighted in the model.
Article
Each person is affected by disease and disability differently. This study examined the role of age and subjective perception of health in determining the links of depressive symptoms with disease and disability among older adults of different ages. The hypothesized effects of age and subjective health were tested using 252 older adults divided into three age groups (i.e., 60s, 80s, and 100s). Two major findings emerged. First, individuals with advanced old age had higher levels of health problems, as expected. However, their perceptions of health and depressive symptoms were less affected by disability when compared to the younger old. Second, regardless of age, the effects of disease and disability on depressive symptoms were mediated through subjective health. Findings suggest age differences in the consequences of health problems, and the importance of subjective perception to bridge physical and mental health. Issues such as age differences within older populations, the resilience of centenarians, and the intervening roles of subjective health are further discussed.
Article
Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases. • psychological stress • telomere length • telomerase • oxidative stress
Article
The factors that determine quality of life (QOL) and disability after traumatic injury are poorly understood. This study identified the unique contributions that characteristics about the injury/hospital admission and acute psychological adjustment make in determining 12-month role-related disability and QOL. Consecutive admissions (n = 363) to a Level I trauma service were assessed just before discharge and followed up at 12 months. Structural equational modeling was used to examine the relationships between the acute factors and 12-month outcomes. Characteristics of the individual's injuries measured in the acute setting significantly predicted 12-month disability but only indirectly predicted 12-month QOL. An individual's acute psychological response directly predicted both the level of disability and QOL at 12 months. Both characteristics about an individual's injury and acute psychological responses play important roles in determining later QOL and role-related disability outcomes. Trauma care systems must consider both physical and psychological injury to offer effective and comprehensive healthcare management.
Article
The predicting value of age on stroke rehabilitation has been controversial. There is a lack of large-scale studies in the Chinese population to examine the effect of age on stroke rehabilitation outcomes. This study examines the predictors of a good outcome after rehabilitation in Chinese stroke patients with special attention to age as a factor. This retrospective cohort study includes stroke patients receiving a standard inpatient multidisciplinary rehabilitation program in a neuro-rehabilitation ward of a convalescence hospital in Hong Kong from January 2000 to December 2003. Functional independence measure (FIM) >or=90 was used to define a good outcome. Multivariate regression analysis was used to assess the independent predictors of a good outcome. There were important differences in clinical characteristics and complications of stroke among patients of three age groups: <65, >or=65 and <80, and >or=80 years. The total FIM scores both upon admission and at discharge were lower in the older age groups. No significant difference was observed in the changes in FIM scores across these age groups. Age was not an independent predictor for a good outcome. FIM upon admission was an independent predictor for a good outcome (discharge FIM >or=90) in all patients and in individual age groups. Having employment before stroke was a predictor for good outcome in all patients. Living at home prior to stroke was a predictor for the total population and the >or=65 and <80 years group. The length of stay predicted a good outcome in the group >or=80 years. Admission functional status, employment and living at home before stroke but not age per se are predictors of a good outcome following stroke rehabilitation. As older patients show comparable improvement during rehabilitation, intensive rehabilitation should not be withheld in stroke patients simply because of advanced age.
Article
Fanconi anaemia (FA) is an autosomal recessive and X-linked disease characterized by severe genetic instability and increased incidence of cancer. One explanation for this instability may be the cellular hypersensitivity to oxidative stress leading to chromosomal breaks. This study explored the possible oxidative damage to telomeres of FA lymphocyte cell line, HSC536/N, and its possible effect on telomere function. We postulated that combination of oxidative damage with overexpression of telomerase may provide a possible model for malignant transformation in FA. The cells were grown in the presence of telomerase inhibitor and exposed for 1 month to H(2)O(2) combined with various antioxidants. This exposure caused shortening of telomere length and damage to the telomere single stranded overhang, which was prevented by several oxidants. This shortening was associated with development of severe telomere dysfunction. Control cells did not exhibit this sensitivity to H(2)O(2). Telomere dysfunction did not evoke damage response in FA cells, in contrast to normal P53 upregulation in control cells. Reconstitution of telomerase activity protected FA telomeres from further oxidative damage. These results suggest a scenario in which oxidative stress causes telomere shortening and ensuing telomere dysfunction may form the basis for malignant transformation in FA cells. Upregulation of telomerase activity in sporadic FA cells may perpetuate that process, thus explaining the malignant character of FA cells in vivo.
The brain on stress: Toward an integrative approach to brain, body, and behavior
  • McEwen
PROCESS: A versatile computational tool for observed variable mediation, moderation, and conditional process modeling
  • A F Hayes
Hayes, A. F. (2012). PROCESS: A versatile computational tool for observed variable mediation, moderation, and conditional process modeling [White Paper]. http://www.afhayes.com.