Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State

Wikgren, Mikael; Maripuu, Martin; Karlsson, Thomas; Nordfjäll, Katarina; Bergdahl, Jan; Hultdin, Johan; Del-Favero, Jurgen; Roos, Göran; Nilsson, Lars‐Göran; Adolfsson, Rolf; Norrbäck, Karl-Fredrik

doi:10.1016/j.biopsych.2011.09.015

Cited by 156 publications

(158 citation statements)

References 64 publications

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“…We have recently shown in a larger study which contained a major depression patient sample consisting of older outpatients (partly overlapping with the patient sample of the present study) which employed the same DST as the one presently used, that major depression patients exhibited both a significantly higher fraction of subjects with an increased negative feedback response compared with controls and the degree of suppression among patient hypersuppressors was more pronounced compared with the control hypersuppressors. 39 The study also confirmed that both patient hypersuppressors and control hypersuppressors exhibited significantly lower basal state cortisol levels providing further support to the claim that an elevated negative feedback response of the HPAaxis is associated with a hypocortisolemic state. 39 Low basal cortisol levels have together with low post-DST cortisol levels, as captured by a low dose DST, as well as a reduced adrenocortiocal reactivity upon challenge (eg, corticotrophin releasing hormone [CRH] or adrenocorticotropic hormone [ACTH] administration) all been recognized as characteristics of hypocortisolism, but one reason why the basal cortisol measure is considered a less reliable marker for hypocortisolism could be the large degree of intra-individual variability observed between the circadian cycles, from day to day.…”

Section: Discussionsupporting

confidence: 72%

Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

Karling

Wikgren

Adolfsson

et al. 2016

J Neurogastroenterol Motil

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Background/AimsGastrointestinal symptoms and hypothalamus-pituitary-adrenal (HPA) axis dysfunction are frequently observed in patients with major depression. The primary aim of the study was to investigate the relationship between HPA-axis function and self-perceived functional gastrointestinal symptoms in major depression. MethodsPatients with major depression (n = 73) and controls representative of the general population (n = 146) underwent a weightadjusted very low dose dexamethasone suppression test (DST). Patients and controls completed the gastrointestinal symptom rating scale-iritable bowel syndrome (GSRS-IBS) and the hospital anxiety depression scale. Medical records of the patients were screened over a ten year period for functional gastrointestinal disorder and pain conditions. ResultsPatients with high GSRS-IBS scores (above median) exhibited HPA-axis hypersuppression more often than controls (defined by the lowest 10% cutoff of the post-DST cortisol values among controls, adjusted OR 7.25, CI 1.97-26.7) whereas patients with low GSRS-IBS scores did not differ from controls concerning their post-DST cortisol values. Patients who had consulted primary care for functional gastrointestinal disorder (P = 0.039), lumbago (P = 0.006) and chronic multifocal pain (P = 0.057) also exhibited an increased frequency of hypersuppression. Conclusions

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Section: Discussionsupporting

confidence: 72%

Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

Karling

Wikgren

Adolfsson

et al. 2016

J Neurogastroenterol Motil

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“…The numbers of men and women in the short TL/high TA groups were similar, but there was no indication of comparable trends in physiological responses (Tables S1 and S2). Studies relating shorter telomeres to life stress have involved both men and women (10,11,14,18,20). Previous research relating telomeres to acute physiological stress responses have been carried out with female but not male samples (15,21,24), although associations between health risk and the combination of shorter telomeres and raised TA have been reported in both men and women (16,25).…”

Section: Discussionmentioning

confidence: 99%

“…One of the factors thought to influence telomere dynamics is psychosocial stress (10,11). Epel et al (12) demonstrated that the severe stress experienced by mothers of chronically ill children was correlated with reduced leukocyte TL.…”

mentioning

confidence: 99%

Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources

Zalli

Carvalho

Lin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Recent work has linked psychological stress with premature cellular aging as indexed by reduced leukocyte telomere length. The combination of shorter telomeres with high telomerase activity (TA) may be indicative of active cell stress. We hypothesized that older individuals characterized by shorter telomeres with high TA in unstimulated leukocytes would show signs of high allostatic load and low levels of protective psychosocial resources. We studied 333 healthy men and women aged 54-76 y who underwent laboratory testing in which we measured cardiovascular, neuroendocrine, and inflammatory responses to standardized mental stress tasks. The tasks elicited prompt increases in blood pressure (BP), heart rate, cortisol, and mediators of inflammation and reductions in heart rate variability, returning toward baseline levels following stress. However, men having shorter telomeres with high TA showed blunted poststress recovery in systolic BP, heart rate variability, and monocyte chemoattractant protein-1, together with reduced responsivity in diastolic BP, heart rate, and cortisol, in comparison to men with longer telomeres or men with shorter telomeres and low TA. Shorter telomeres with high TA were also associated with reduced social support, lower optimism, higher hostility, and greater early life adversity. These effects were independent of age, socioeconomic status, and body mass index. We did not observe differences among older women. Our findings suggest that active cell stress is associated with impaired physiological stress responses and impoverished psychosocial resources, reflecting an integration of cellular, systemic, and psychological stress processes potentially relevant to health in older men. cellular senescence | allostasis | psychological distress T elomeres are nucleoprotein structures composed of tandem hexanucleotide repeats of the sequence TTAGGG that cap the ends of eukaryotic chromosomes, protecting them from end-to-end fusion and degradation during cell division. Human telomeric DNA naturally shortens with age during somatic cell divisions and as a result of oxidative attack (1, 2). At critical shortness, telomeres exhibit impaired function, leading to genomic instability, apoptosis, and cell senescence, often with altered transcriptional programming and mitochondrial dysfunction (1). Telomere attrition represents one of the hallmarks of aging (3). In humans, Mendelian singlegene mutations that directly compromise telomere maintenance cause premature mortality and onset of a spectrum of diseases overlapping with the age-related diseases common in the population (4). In addition, genome-wide association studies show that certain combinations of SNPs at genetic loci encoding known telomere-maintenance factors are associated with increased relative risks for pulmonary and coronary diseases (5). Shorter telomere length (TL) in white blood cells is linked and, in some cases, anticipates aging-related morbidity and mortality from conditions with immune system involvement, such as infectious disease...

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“…Stress is a natural reaction of the human body to an outside perturbing factor. The physiological responses to stress are correlated with variations in heart rate, blood volume pulse, skin temperature, pupil dilation, electro-dermal activity [18,17,13]. Stress may have beneficial effects on fighting the stress factor, like increasing reflexes, but it was determined that long term stress is correlated with various health problems like depression and premature ageing [16], [9].…”

Section: Introductionmentioning

confidence: 99%

Stress Detection Using Wearable Physiological Sensors

Sandulescu

Andrews

Ellis

et al. 2015

Lecture Notes in Computer Science

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Abstract. As the population increases in the world, the ratio of health carers is rapidly decreasing. Therefore, there is an urgent need to create new technologies to monitor the physical and mental health of people during their daily life. In particular, negative mental states like depression and anxiety are big problems in modern societies, usually due to stressful situations during everyday activities including work. This paper presents a machine learning approach for stress detection on people using wearable physiological sensors with the final aim of improving their quality of life. The presented technique can monitor the state of the subject continuously and classify it into "stressful" or "non-stressful" situations. Our classification results show that this method is a good starting point towards real-time stress detection.

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Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State

Cited by 156 publications

References 64 publications

Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression

Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources

Stress Detection Using Wearable Physiological Sensors

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