Depression gets old fast: Do stress and depression accelerate cell aging? Depression and Anxiety, 27(4), 327-338

Depression and Anxiety (Impact Factor: 4.41). 04/2010; 27(4):327 - 338. DOI: 10.1002/da.20686


Depression has been likened to a state of “accelerated aging,” and depressed individuals have a higher incidence of various diseases of aging, such as cardiovascular and cerebrovascular diseases, metabolic syndrome, and dementia. Chronic exposure to certain interlinked biochemical pathways that mediate stress-related depression may contribute to “accelerated aging,” cell damage, and certain comorbid medical illnesses. Biochemical mediators explored in this theoretical review include the hypothalamic–pituitary–adrenal axis (e.g., hyper- or hypoactivation of glucocorticoid receptors), neurosteroids, such as dehydroepiandrosterone and allopregnanolone, brain-derived neurotrophic factor, excitotoxicity, oxidative and inflammatory stress, and disturbances of the telomere/telomerase maintenance system. A better appreciation of the role of these mediators in depressive illness could lead to refined models of depression, to a re-conceptualization of depression as a whole body disease rather than just a “mental illness,” and to the rational development of new classes of medications to treat depression and its related medical comorbidities. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.

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    • "Thus, the association between rs7676614 and symptoms of retardation may not only explain the lack of a stronger link between the SNP and overall MDD diagnosis, but also offer mechanistic clues as to the specific biological pathway through which this SNP may increase MDD risk. A largely independent line of research drawing on human postmortem gene expression data has demonstrated a significant overlap between molecular pathways implicated in depression and normal aging (Wolkowitz et al., 2010; Sibille, 2013). Specifically, it has been proposed that MDD or risk thereof may stem at least partially from molecular processes resulting in gene expression patterns reminiscent of premature, or accelerated, aging of the brain (Douillard-Guilloux et al., 2013; Sibille, 2013). "
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    ABSTRACT: The A allele of the FRAS1-related extracellular matrix protein 3 (FREM3) rs7676614 single nucleotide polymorphism (SNP) was linked to major depressive disorder (MDD) in an early genome-wide association study (GWAS), and to symptoms of psychomotor retardation in a follow-up investigation. In line with significant overlap between age-and depression-related molecular pathways, parallel work has shown that FREM3 expression in postmortem human brain decreases with age. Here, we probe the effect of rs7676614 on amygdala reactivity and perceptual processing speed, both of which are altered in depression and aging. Amygdala reactivity was assessed using a face-matching BOLD fMRI paradigm in 365 Caucasian participants in the Duke Neurogenetics Study (DNS) (192 women, mean age 19.7 ± 1.2). Perceptual processing speed was indexed by reaction times in the same task and the Trail Making Test (TMT). The effect of rs7676614 on FREM3 mRNA brain expression levels was probed in a postmortem cohort of 169 Caucasian individuals (44 women, mean age 50.8 ± 14.9). The A allele of rs7676614 was associated with blunted amygdala reactivity to faces, slower reaction times in the face-matching condition (p < 0.04), as well as marginally slower performance on TMT Part B (p = 0.056). In the postmortem cohort, the T allele of rs6537170 (proxy for the rs7676614 A allele), was associated with trend-level reductions in gene expression in Brodmann areas 11 and 47 (p = 0.066), reminiscent of patterns characteristic of older age. The low-expressing allele of another FREM3 SNP (rs1391187) was similarly associated with reduced amygdala reactivity and slower TMT Part B speed, in addition to reduced BA47 activity and extraversion (p < 0.05). Together, these results suggest common genetic variation associated with reduced FREM3 expression may confer risk for a subtype of depression characterized by reduced reactivity to environmental stimuli and slower perceptual processing speed, possibly suggestive of accelerated aging.
    Frontiers in Psychology 10/2015; 6. DOI:10.3389/fpsyg.2015.01377 · 2.80 Impact Factor
    • "Therefore, such psychosocial stress, both early in life as well as more recent stress, is assumed to affect biological systems, such as the immune system (Segerstrom and Miller, 2004), autonomic nervous system, and hypothalamic– pituitary–adrenal (HPA) axis (Geenen et al., 2006). These disrupted stress systems have been associated with increased levels of oxidative stress, which in turn may accelerate cellular aging (Wolkowitz et al., 2010). One widely used indicator of cellular aging is TL. "
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    ABSTRACT: Psychosocial stress has been associated with an increased risk for mental and somatic health problems across the life span. Some studies in younger adults linked this to accelerated cellular aging, indexed by shortened telomere length (TL). In older adults, the impact of psychosocial stress on TL may be different due to the lifetime exposure to competing causes of TL-shortening. This study aims to assess whether early and recent psychosocial stressors (childhood abuse, childhood adverse events, recent negative life events, and loneliness) were associated with TL in older adults. Data were from the Netherlands Study of Depression in Older Persons (NESDO) in which psychosocial stressors were measured in 496 persons aged 60 and older (mean age 70.6 (SD 7.4) years) during a face-to-face interview. Leukocyte TL was determined using fasting blood samples by performing quantitative polymerase chain reaction (qPCR) and was expressed in base pairs (bp). Multiple regression analyses, adjusted for age, sex, and chronic diseases, showed that childhood abuse, recent negative life events and loneliness were unrelated to TL. Only having experienced any childhood adverse event was weakly but significantly negatively associated with TL. Our findings did not consistently confirm our hypothesis that psychosocial stress is associated with shorter TL in older adults. Healthy survivorship or other TL-damaging factors such as somatic health problems seem to dominate a potential effect of psychosocial stress on TL in older adults.
    International Psychogeriatrics 08/2015; DOI:10.1017/S1041610215001155 · 1.93 Impact Factor
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    • "This may be due in part to possible neuropathological contributors of each disorder including white matter damage, not assessed in the study. For example, a recent review suggests that depression might represent accelerated cellular aging, reflected in abnormalities in cortisol, neurotrophic factors, oxidative damage, and telomere length (Wolkowitz et al., 2010). Diabetes may play a role in brain aging as well. "
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    ABSTRACT: Objective The purpose of this study was to examine the relationship between verbal learning and memory performance and hippocampal volume in subjects with co-morbid type 2 diabetes and major depression compared with healthy control subjects and subjects with type 2 diabetes alone. Methods Twenty four subjects with type 2 diabetes and 20 subjects with type 2 diabetes and major depression were recruited from endocrinology clinics and were compared with 32 healthy control subjects recruited from the community. Subjects were scanned on a 1.5 T GE scanner, and hippocampal volumes were measured using Freesurfer. The California Verbal Learning Test assessed learning and memory. Significant predictors of verbal learning performance (e.g., age, gender, education, blood pressure, stroke risk, hemoglobin A1c, and hippocampal volume) were determined using a stepwise linear regression. ResultsSubjects with diabetes and depression had significantly worse performance on verbal list learning compared with healthy control subjects. Hippocampal volume was a strong predictor of performance in healthy control subjects, and age and hippocampal volume were strong predictors in subjects with type 2 diabetes alone. Age alone was a significant predictor of verbal learning performance in subjects with diabetes and depression. Conclusions The relationship between hippocampal volume and performance on the California Verbal Learning Test is decoupled in subjects with type 2 diabetes and major depression and this decoupling may contribute to poor verbal learning and memory performance in this study population. Copyright (c) 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 04/2015; 30(4). DOI:10.1002/gps.4149 · 2.87 Impact Factor
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