DST
Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) [BP230] [BP240] [BPAG1] [DMH] [DT] [KIAA0728]
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Life has persisted for about 3.5 billion years (Gy) despite fluctuating environmental pressures and the aging and mortality of individuals. The disposable soma theory (DST) notoriously contributes to explain this persistence for lineages with a clear soma/germen distinction. Beyond such lineages however, the phylogenetic scope of application of the DST is less obvious. Typically, the DST is not expected to explain the survival of microbial species that comprise single-celled organisms apparently lacking a germen/soma distinction. Here, we present an evolutionary argument that generalizes the explanatory scope of DST to the entire microbial world and provides a novel characterization of the deep molecular and evolutionary roots supporting this expanded disposable soma theory of aging. Specifically, we argue that the germen/soma distinction arose early in evolution and identify DNA semi-conservative replication as a critical process through which two forms of rejuvenation could have evolved in the first microbes. Our hypothesis has fundamental and practical implications. First, whereas unicellular organisms were long thought of as potentially immortal, we suggest instead that all unicellular individuals (prokaryotes or protists alike) are very likely to age, either replicatively or physiologically, or both. Second, our theory introduces a profound reconsideration of microbial individuality, whereby, all microbial individuals, as seen by natural selection, present an obligate transient germen/soma distinction during their life cycles. Third, our work promotes the study of cellular division in prokaryotes and in protist mitosis to illuminate the evolutionary origin of the soma and germen division, traditionally studied in animals. These ideas set the stage for progress in the evolutionary theory of aging from a heretofore overlooked microbial perspective.
MeSH Terms
- Aging
- Animals
- Biological Evolution
- DNA Replication
- Humans
- Phylogeny
Keywords
- Aging
- Asymmetric cell division
- DNA replication
- Disposable Soma Theory
- Epigenetics
- Evolution
- Germen/Soma
- Prokaryotes
- Protists
- Rejuvenation
- Unicellular
Diet quality has been associated with health outcomes and quality of life. However, the association between diet quality and mortality in older people, those aged 80 years and older, is understudied. Therefore, we conducted a prospective study to examine whether better diet quality, assessed by a validated dietary screening tool (DST), was associated with lower mortality in those aged 80 years and older. Our study included 1990 participants (812 men and 1178 women), with a mean age of 84.1 years at baseline (ranging from 80 to 102 years old), from the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Baseline descriptive information was obtained in 2009, and the DST was administered via mailed survey. The DST is composed of 25 food- and behavior-specific questions associated with dietary intake that generate a diet quality score ranging from 0 (lowest) to 100 (highest). Death was identified using electronic medical record and the Social Security Death Index data. Hazard ratios (HRs) and 95% confidence intervals (CIs) across three diet quality categories were calculated by using Cox proportional hazards models after adjusting for potential confounders. Over 8 years of follow-up (October 2009-February 2018), 931 deaths were documented. Higher diet quality was associated with lower mortality risk (P-trend = .04). Participants with high diet quality (defined as DST scores >75) had significantly lower risk of mortality compared with those with low diet quality (defined as DST scores <60) after adjusting for potential risk factors (adjusted HR = 0.76; 95% CI = 0.59-0.97). Diet quality, assessed by DST, is significantly associated with risk of mortality in older adults aged 80 years and older in our prospective cohort. Our results indicate that nutrition may have an important role in healthy aging, and more studies are needed to develop appropriate dietary recommendations for older persons. J Am Geriatr Soc 67:2180-2185, 2019.
MeSH Terms
- Aged, 80 and over
- Diet, Healthy
- Feeding Behavior
- Female
- Healthy Aging
- Humans
- Male
- Mortality
- Nutritional Status
- Prospective Studies
- Quality of Life
- Risk Assessment
- Surveys and Questionnaires
Keywords
- diet quality
- dietary pattern
- healthy aging
- mortality
- older people
To determine the associations between diet quality, body mass index (BMI), and health-related quality of life (HRQOL) as assessed by the health and activity limitation index (HALex) in older adults. Multivariate linear regression models were used to analyze associations between Dietary Screening Tool (DST) scores, BMI and HALex score, after controlling for gender, age, education, living situation, smoking, disease burden and self-vs. proxy reporting. Geisinger Rural Aging Study, Pennsylvania. 5,993 GRAS participants were mailed HRQOL and DST questionnaires with 4,009 (1,722 male, 2,287 female; mean age 81.5 ± 4.4) providing complete data. HALex scores were significantly lower for participants with dietary intakes categorized as unhealthy (<60) (0.70, 95% CI 0.69, 0.72, p<0.05) or borderline (60-75) (0.71, 95% CI 0.70, 0.73, p<0.05) compared to those scoring in the healthy range (>75) (0.75, 95% CI 0.73, 0.77) based on DST scores. HALex scores were significantly lower for underweight (0.67, 95% CI 0.63, 0.72, p<0.05), obese class II (0.68, 95% CI 0.66, 0.71, p<0.05) and class III participants (0.62 95% CI 0.57, 0.67, p<0.05) compared to those with BMI 18.5-24.9. Poor diet quality, as assessed by the DST, is associated with lower HRQOL in adults ≥ 74 years of age.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Body Mass Index
- Cross-Sectional Studies
- Diet
- Female
- Health Behavior
- Humans
- Male
- Motor Activity
- Nutrition Assessment
- Obesity
- Pennsylvania
- Quality of Life
- Rural Population
- Surveys and Questionnaires
- Thinness
Aging is associated with an increased risk of depression in humans. To elucidate the underlying mechanisms of depression and its dependence on aging, here we study signs of depression in male SAMP8 mice. For this purpose, we used the forced swimming test (FST). The total floating time in the FST was greater in SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not observed in 12-month-old mice, when both strains are considered elderly. Of the two strains, only the SAMP8 animals responded to imipramine treatment. We also applied the dexamethasone suppression test (DST) and studied changes in the dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in the cortex, and levels of TPH2. The DST showed a significant difference between SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8 mice presented depression-like behavior that is dependent on senescence process, because it differs from SAMR1, senescence resistant strain.
MeSH Terms
- Aging
- Animals
- Antidepressive Agents, Tricyclic
- Behavior, Animal
- Cerebral Cortex
- Depression
- Disease Models, Animal
- Dopamine
- Imipramine
- Incidence
- Male
- Mice
- Mice, Inbred Strains
- Receptors, Serotonin
- Swimming
- Treatment Outcome
- Tryptophan Hydroxylase
The swallowing mechanism changes significantly as people age, even in the absence of chronic diseases. Presbyphagia, a term that refers to aging-related changes in the swallowing mechanism, may be linked to many health conditions and presents itself in distinct ways. Swallowing disorders are also identified as a major problem amongst the elderly population living in nursing homes. The study sought to determine the prevalence of swallowing disorders in nursing home residents, to identify the relationship between self-perceived swallowing disorders, cognitive functions, autonomy, and depression, and also to analyze which variables explain the score of the Dysphagia Self-Test (DST). For this purpose, the researchers chose to apply a survey conveying questions on demographic aspects, general health, eating and feeding, as well as instruments to assess functional performance and the 3 ounce Water Swallow Test. The sample consisted of 272 elderly people living in eight nursing homes in Portugal. Six did not sign the informed consent form. Of the total, 29% were totally dependent, 33% were depressed, 45% had cognitive impairment, and 38% needed help with feeding. About 43% of the individuals reported having problems related to eating. Regarding the DST, 40% showed signs of dysphagia. With respect to the 3 ounce Water Swallow Test, 38% revealed at least one of the symptoms, wet voice being the most prevalent. Correlation measures showed that age had no linear association with the DST score although correlation with the Barthel Index and Mini Mental State Examination was found to be significant. A linear regression model was estimated with the DST score as the dependent variable and the MMSE and BI scores, gender, age, education, the Geriatric Depression Scale score, 3 ounce Water Swallow Test, and diagnosed conditions (such as neurological disorder, dementia, and cardiorespiratory problems) as explaining variables. Results showed a high prevalence of dysphagia signs amongst a nursing home population. For the purpose of the present study, both a subjective and an objective assessment were applied. Results pointed to a significant statistical relation between objective and subjective measures, thus indicating that a self-perception test should be included in the assessment of swallowing disorders in a nursing home population. Notwithstanding, it should not be used as a single or principal measure as it is influenced by the individuals' cognitive condition.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Cognition
- Cross-Sectional Studies
- Deglutition Disorders
- Depression
- Female
- Geriatric Assessment
- Homes for the Aged
- Humans
- Male
- Nursing Homes
- Prevalence
- Self Concept
Keywords
- deglutition
- deglutition disorders
- elderly
Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70-74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P=0·004), m-DST (10·5 v. 9·8, P=0·005) and m-MMSE (11·5 v. 11·4, P=0·01). A generalised additive regression model showed a positive dose-response relationship between the m-MMSE and choline (P=0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B₁₂ (≤257 pmol/l) concentrations (RR(KOLT)=2·6, 95 % CI 1·1, 6·1; RR(m-MMSE)=2·7, 95 % CI 1·1, 6·6; RR(COWAT)=3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) (≥3·95 μmol/l) concentrations (RR(m-BD)=2·8, 95 % CI 1·3, 6·1). Low betaine (≤31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RR(KOLT)=2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B₁₂ or high MMA on cognitive performance.
MeSH Terms
- Aged
- Aging
- Betaine
- Biomarkers
- Choline
- Choline Deficiency
- Cognitive Dysfunction
- Cohort Studies
- Cross-Sectional Studies
- Diet
- Female
- Follow-Up Studies
- Geriatric Assessment
- Humans
- Male
- Methylmalonic Acid
- Norway
- Risk Factors
- Statistics as Topic
- Vitamin B 12
- Vitamin B 12 Deficiency
Studies of clinical uses of brain natriuretic peptide (BNP) represent one of the most important advances in cardiology since the introduction of echocardiography as a clinical diagnostic procedure. Defining the clinical potential of BNP in canine cardiology has not been completed yet. The aim of this study is to measure BNP concentrations in healthy German Shepherd dogs of different ages as a baseline in resting and when conventional protocol of the dobutamine stress test (DST) is applied to dogs. Concentrations of BNP were measured in blood serum by the radioimmunoassay method. The values of BNP concentrations were compared to cardiac parameters obtained by standard cardiac diagnostic procedures (radiology, electrocardiography and echocardiography). No significant differences in serum BNP concentrations existed in dogs of different ages. A statistically significant increase in BNP concentrations was registered after DST. These changes in BNP concentrations were related to ST/T electrocardiographic changes, and correlated to changes in the left ventricular internal diameter in systole (LVESD). These data suggest that BNP is not increased in aged dogs with normal cardiac systolic function and renal function, and that myocardial ischemia leads to a significant increase in BNP concentrations even in dogs with normal left ventricular function.
MeSH Terms
- Aging
- Animals
- Brain
- Cardiotonic Agents
- Dobutamine
- Dogs
- Echocardiography, Stress
- Female
- Gene Expression Regulation
- Male
- Natriuretic Peptide, Brain
Inflammation plays a significant role in Alzheimer's disease (AD) pathogenesis. Studies have shown that systemic, peripheral infections affect AD patients. Cognitive dysfunction is a consistent finding in AD and periodontal disease is a chronic, peripheral infection often resulting in tooth loss. We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few missing teeth. The effect of PI/tooth loss on cognitive function [measured by Digit Symbol (DST) and Block Design (BDT) tests] was assessed in 70-year old Danish subjects. We found: 1) subjects with PI obtained lower mean DST scores compared to subjects without PI (p < 0.05); 2) subjects with many missing teeth had lower mean DST and BDT scores compared to subjects with few missing teeth (p < 0.05); 3) the association of PI with DST and BDT scores was dependant on the number of missing teeth (interaction: p = 0.03 and p = 0.06); and 4) education and previous cognitive scores (age 50) were important covariates. Subjects with PI had significantly lower adjusted mean DST scores compared to subjects without PI. However for adjusted BDT, the significance held only for subjects with few missing teeth. No difference in the adjusted DST and BDT scores was seen between subjects with many missing teeth compared to those with few missing teeth. These results support the hypothesis that PI may affect cognition.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Analysis of Variance
- Cognition Disorders
- Denmark
- Female
- Humans
- Inflammation
- Longitudinal Studies
- Male
- Neuropsychological Tests
- Periodontal Diseases
- Tooth Loss
A major factor influencing life-history strategies of endotherms is body size. Larger endotherms live longer, develop more slowly, breed later and less frequently, and have fewer offspring per attempt at breeding. The classical evolutionary explanation for this pattern is that smaller animals experience greater extrinsic mortality, which favors early reproduction at high intensity. This leads to a short lifespan and early senescence by three suggested mechanisms. First, detrimental late-acting mutations cannot be removed because of the low force of selection upon older animals (mutation accumulation). Second, genes that promote early reproduction will be favored in small animals, even if they have later detrimental effects (antagonistic pleiotropy). Third, small animals may be forced to reduce their investment in longevity assurance mechanisms (LAMs) in favor of investment in reproduction (the disposable soma theory, DST). The DST hinges on three premises: that LAMs exist, that such LAMs are energetically expensive and that the supply of energy is limited. By contrast, the heat dissipation limit (HDL) theory provides a different conceptual perspective on the evolution of life histories in relation to body size. We suggest that rather than being limited, energy supplies in the environment are often unlimited, particularly when animals are breeding, and that animals are instead constrained by their maximum capacity to dissipate body heat, generated as a by-product of their metabolism. Because heat loss is fundamentally a surface-based phenomenon, the low surface-to-volume ratio of larger animals generates significant problems for dissipating the body heat associated with reproductive effort, which then limits their current reproductive investment. We suggest that this is the primary reason why fecundity declines as animal size increases. Because large animals are constrained by their capacity for heat dissipation, they have low reproductive rates. Consequently, only those large animals living in habitats with low extrinsic mortality could survive leading to the familiar patterns of life-history trade-offs and their links to extrinsic mortality rates. The HDL theory provides a novel mechanism underpinning the evolution of life history and ageing in endotherms, and makes a number of testable predictions that directly contrast with the predictions arising from the DST.
MeSH Terms
- Aging
- Animals
- Biological Evolution
- Body Mass Index
- Body Size
- Body Temperature Regulation
- Energy Metabolism
- Longevity
- Models, Biological
- Reproduction
Results of diagnostic tests for equine pituitary pars intermedia dysfunction (PPID), including endogenous ACTH concentration and the overnight dexamethasone suppression test (DST), are affected by season. New and potentially more sensitive diagnostic tests for equine PPID, such as thyrotropin-releasing hormone (TRH)-stimulated ACTH response, have been developed, but have had limited evaluation of seasonality. Our purpose was to evaluate seasonal changes in plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) responses to TRH administration. Nine, healthy, aged horses with normal DST results. Synthetic TRH (1 mg) was administered IV. Plasma ACTH and α-MSH concentrations were measured at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 180 minutes. Testing was performed in February, July, August, September, October, and November. Mean TRH-stimulated ACTH and α-MSH concentrations were compared across months and time by repeated measures analysis of variance. Significance was set at the P < .05 level. Concentrations of ACTH and α-MSH significantly increased after TRH administration. Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February. Plasma ACTH and α-MSH responses to TRH administration experience seasonal variation, with TRH-stimulated ACTH and α-MSH concentrations increasing from summer through fall. These results support previous evidence of a seasonal influence on the equine pituitary-adrenal axis. More research is warranted with a larger number of horses to determine if seasonal reference ranges for TRH stimulation testing need to be defined.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Female
- Horses
- Male
- Reference Values
- Seasons
- Thyrotropin-Releasing Hormone
- Time Factors
- alpha-MSH
The purpose of this study was to evaluate the variation in plasma adrenocorticotropic hormone (ACTH) concentration and dexamethasone suppression test (DST) results with season, age, and sex in healthy, pony mares (n=15) and pony stallions (n=14) living under semiferal conditions and horse mares (n=10) living at pasture. Plasma ACTH concentrations were measured in September 2002, and in January, May, and September 2003. DSTs were performed in January and September 2003. Plasma ACTH concentrations in September 2002 and September 2003 were similar and were significantly greater than in January and May (P < .001). Plasma ACTH concentration was within the reference range for 38 (97%) of 39 subjects in January, for 39 (100%) of 39 subjects in May, for 2 (5%) of 39 subjects in September 2002, and for 3 (8%) of 39 subjects in September 2003. DST results were within the reference range in all subjects in January and were within the reference range for 29 (74%) of 39 subjects in September 2003. Plasma cortisol concentration at the end of the DST was significantly greater in September than in January (P = .002). Age was positively correlated with plasma ACTH and plasma cortisol concentration at the beginning and end of the DST Within the same season, plasma ACTH concentration in pony mares, pony stallions, and horse mares was not significantly different (P > .05). Seasonal changes in plasma ACTH concentration and DST results should be considered when interpreting endocrine test results.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Body Size
- Cushing Syndrome
- Dexamethasone
- Female
- Horse Diseases
- Horses
- Male
- Seasons
- Sex Factors
Convincing evidences has linked the hypothalamus-pituitary-adrenal (HPA) axis to aging patterns. F excess is implicated in the development of frailty characteristics whereas DHEAS is positively correlated to successful aging. We compared serum F and DHEAS levels of independent community-living (successful group, 19 M and 28 F, 69 to 87 yr) with those of institutionalized elderly (frail group, 20 M and 30 F, 65 to 95 yr). Serum F was determined at 1) baseline (08:00 h, 16:00 h and 23:00 h), 2) after 2 overnight dexamethasone (DEX) suppression tests (DST, using 0.25 and 1.0 mg doses), and 3) 60 min after ACTH stimulation (250 microg i.v. bolus); serum DHEAS was determined at 08:00 h. Basal serum F at 08:00 h, 16:00 h and 23:00 h and serum DHEAS levels were similar in both groups; however F: DHEAS ratio at 08:00 h was higher in the frail, compared to the successful group (mean /- SD: 0.55 /- 0.53 and 0.35 /- 0.41, respectively; p = 0.04). In response to DST, F suppression was less effective in frail elderly after either 0.25 or 1.0 mg doses (9.0 /- 6.0 and 2.0 /- 0.9 microg/dl), as compared to the successful group (5.8 /- 4.4 and 1.5 /- 0.5 microg/dl) (p = 0.01). In addition, a significant correlation was observed between post-DEX F levels (both doses) and parameters of cognitive and physical frailty. Normal and similar F levels were observed after ACTH stimulation in both groups. Our data suggest a deficient feedback regulation of the HPA axis in frail institutionalized elderly, as demonstrated by a higher set point for F suppression. This augmented HPA tonus enforces the hypothesis that even milder F excess may be related to characteristics of frailty in the elderly.
MeSH Terms
- Activities of Daily Living
- Adrenocorticotropic Hormone
- Aged
- Aged, 80 and over
- Aging
- Circadian Rhythm
- Cognition
- Dehydroepiandrosterone Sulfate
- Dexamethasone
- Drug Resistance
- Female
- Frail Elderly
- Glucocorticoids
- Humans
- Hydrocortisone
- Institutionalization
- Male
The present study further examined relationships between postdexamethasone cortisol plasma values and sleep electroencephalogram (EEG) parameters. The dexamethasone suppression test (DST) and polysomnographic recordings were performed in a sample of 300 inpatients with primary major depressive disorder (MDD) (102 men and 198 women, mean age 44 /- 12 years, range 20-74 years) consecutively admitted to Erasme Hospital (Brussels, Belgium) between 1981 and 1992. The DST was abnormal in 40% of the sample. Postdexamethasone cortisol plasma values at 4:00 PM were significantly influenced by age, but not by gender. They were also significantly and positively correlated with weight loss, total scores on the Hamilton Depression Rating Scale, total scores on the Newcastle Scale, percentage of awakenings during sleep, and percent of stage 1. They were significantly and negatively correlated with percent of stage 2, slow-wave sleep, and REM sleep. Multiple regression analyses were conducted in two successive steps. First among clinical variables, only age and depressive symptom severity remained correlated with postdexamethasone plasma cortisol values. In the second step, with age and severity held constant, postdexamethasone plasma cortisol values were positively associated with amount of wake time and stage 1, and negatively with amount of slow-wave sleep. These findings provide further indirect support for an overarousal state in MDD with sympathoadrenal system hyperactivity and impaired sleep continuity. They also underline the importance of taking into account various clinical confounding factors in the interpretation of both DST and sleep EEG results.
MeSH Terms
- Adult
- Aged
- Aging
- Depressive Disorder
- Dexamethasone
- Electroencephalography
- Female
- Hormones
- Humans
- Hydrocortisone
- Male
- Middle Aged
- Multivariate Analysis
- Polysomnography
- Psychiatric Status Rating Scales
- Sex Characteristics
- Sleep
Dysregulation of the hypothalamus-pituitary-adrenal axis (HPA) is more common in elderly patients with depression than in younger depressed patients, and glucocorticoids are known to influence serotonergic function. Elderly depressed patients are also reportedly more resistant to therapeutic effects of antidepressants. In the current study, we measured platelet serotonin transporter binding sites and transport function in young and elderly depressed patients and determined the relationship to HPA status as assessed with the dexamethasone suppression test (DST). The density and affinity of transporter molecules showed no differences between young and elderly depressed patients, regardless of DST results. Nevertheless, transporter function showed a substantial interaction of aging with DST: elderly DST suppressors showed a deficit in [3H]serotonin uptake capabilities and resistance to imipramine inhibition of uptake. No such defects were seen in the young depressed cohort, regardless of DST status, nor in elderly depressed DST non-suppressors. These results are consistent with the view that depression in the elderly exhibits basic biological differences from depression in earlier life, and that such distinctions may account in part for therapeutic ineffectiveness of antidepressants in specific subgroups, associated with the presence or absence of appropriate HPA regulation.
MeSH Terms
- Adult
- Aged
- Aging
- Antidepressive Agents, Tricyclic
- Biological Transport
- Blood Platelets
- Depressive Disorder
- Dexamethasone
- Female
- Glucocorticoids
- Humans
- Hypothalamo-Hypophyseal System
- Imipramine
- Male
- Middle Aged
- Pituitary-Adrenal System
- Receptors, Serotonin
The dexamethasone suppression test (DST) is considered an indicator of the function of the adrenal pituitary axis. The effect of the steroid is mediated by its binding to corticosteroid receptors. We previously suggested that the measurement of corticosteroid receptors in lymphocytes is an index of an analogous pattern in brain. In the present study, corticosteroid Type I and Type II receptors in mononuclear leukocytes were measured in 10 elderly subjects and in 9 young adults, before and after overnight DST (1 mg). Receptors were measured by radioreceptor assay. In all the subjects, dexamethasone was able to suppress plasma cortisol. The number of Type I and Type II receptors before the test was lower in elderly subjects than in adults. In the control group, dexamethasone produced a significant depression of Type I receptors (from 267 /- 72 to 169 /- 71 receptors per cell), which can be interpreted as a primary involvement of Type I receptors in the response to dexamethasone; Type II receptors decreased in half the subjects (from 2849 /- 703 to 2345 /- 569 receptors per cell). In elderly healthy subjects, Type II receptors were also significantly decreased (from 1796 /- 671 to 720 /- 345). We suggest that in young subjects Type II receptors are initially up-regulated by dexamethasone, and then down-regulated, while in aged subjects an up-regulation cannot be achieved, as suggested by the higher values of plasma cortisol usually found in aging subjects.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Aldosterone
- Dexamethasone
- Glucocorticoids
- Humans
- Hydrocortisone
- Leukocytes, Mononuclear
- Male
- Middle Aged
- Receptors, Steroid
The pharmacokinetics of amitriptyline (AMI) have been extensively studied, and a large interindividual variability between oral dose and concentration of the drug in plasma has been documented. The aim of this study was twofold: first, to compare AMI kinetics in depressed patients with those of healthy controls and, second, to describe the relationship between AMI levels in plasma and hypothalamic-pituitary-adrenal (HPA) system changes during depression. Thirty-eight patients with a DSM-III-R diagnosis of major depression and 13 healthy control persons received 75 mg of AMI daily for 6 weeks. Levels of AMI and nortriptyline in plasma were determined, and neuroendocrine testing with the combined dexamethasone-suppression/CRH-stimulation test (DST) was done before AMI administration and after weeks 1, 3, and 6 of medication. AMI levels in plasma were significantly higher in the patient group compared with controls during the entire treatment period, whereas nortriptyline levels did not differ between the two groups. Drug levels correlated significantly with age, but gender had no effect on the concentration of the drug in plasma. Twenty-two patients remitted after treatment. There was no difference in drug levels between responders and nonresponders. Fifteen patients were DST nonsuppressors before treatment; 23 patients and all controls suppressed cortisol after dexamethasone. DST suppressors had significantly higher AMI levels in plasma at weeks 3, 5, and 6 compared with DST nonsuppressors. In comparison to patients with high AMI levels in plasma, those with low drug concentration had higher postdexamethasone cortisol and adrenocorticotropic hormone levels and an increased hormone release after additional CRH.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Amitriptyline
- Antidepressive Agents, Tricyclic
- Depressive Disorder
- Dexamethasone
- Female
- Humans
- Hypothalamo-Hypophyseal System
- Male
- Middle Aged
- Nortriptyline
- Pituitary-Adrenal Function Tests
- Pituitary-Adrenal System
- Psychiatric Status Rating Scales
- Sex Characteristics
The dexamethasone suppression test (DST) was developed from the neuroendocrine research strategy to provide indirect information about the integrity of the limbic system in patients with endogenous depression (ED). Abnormal test results occur in close temporal relationship to clinical episodes of ED, but not during the intervals between episodes. The neuroendocrine disinhibition revealed by the test is not a trait marker of individuals predisposed to develop ED. A standardized DST procedure has been established and can be applied in outpatient or inpatient routine clinical practice, with good sensitivity (50-65%) and high specificity (96%). The conditional probability principles of interpreting the test results are discussed and the effect of prevalence on the predictive value of the test results is emphasized. The DST should not be used as a screening test for all psychiatric patients but should be reserved for cases where clinical indications for its use are present. These indications include diagnostic confirmation of ED, monitoring the response to treatment, prediction of relapse or new episodes, and possibly prediction of suicide risk in patients with ED. The test may be especially useful in the diagnostic assessment of patients with difficult or confusing presentations of ED such as catatonia, depressive pseudodementia, depression in adolescents or children, "masked" depression, depression complicated by a personality disorder, and schizoaffective depression.
MeSH Terms
- Aging
- Catatonia
- Depressive Disorder
- Dexamethasone
- Factitious Disorders
- False Positive Reactions
- Half-Life
- Humans
- Personality Disorders
- Psychotic Disorders
- Suicide
The plasmatic levels of free, sulfoconjugated and total dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of noradrenaline, have been measured in thirty DSM3 major depressive inpatients and in thirty healthy controls matched for sex and age. DOPEG levels have been measured by a radioenzymatic assay. Almost fifty per cent of depressed inpatients were D.S.T. non suppressors, thirteen patients were unipolar and thirteen bipolar. Plasmatic DOPEG levels were significantly lower in depressed patients as compared to healthy controls despite a wide interindividual range of DOPEG values. However, the ratio of free over conjugated DOPEG was not statistically different in the two groups. DOPEG levels were slightly higher in the female population of healthy volunteers but not in the depressed patients. In the healthy volunteers, but not in depressed patients, there was a trend for free DOPEG to increase and for conjugated DOPEG to decrease with age. There was no statistical correlation between the DOPEG levels and Hamilton Depression Scores. Also plasmatic DOPEG values were not different in uni or bipolar patients and in DST suppressor or DST non suppressor inpatients. The significance of the decrease of plasmatic DOPEG levels in depressed patients is discussed: this diminution may reflect a deficiency in noradrenaline metabolism in CNS or else may be attributed to other factors e.g. alteration in circadian rhythms, differences in motor activity, in level of anxiety, in sleep and feeding behaviors; cotreatment with benzodiazepine and opiate compounds; monoamine oxidase activity.
MeSH Terms
- Adult
- Aged
- Aging
- Bipolar Disorder
- Brain
- Circadian Rhythm
- Depressive Disorder
- Dexamethasone
- Female
- Glycols
- Humans
- Male
- Methoxyhydroxyphenylglycol
- Middle Aged
- Norepinephrine
- Pituitary-Adrenal Function Tests
- Recurrence
Dexamethasone suppression tests (DSTs) were performed for 18 moderately demented elderly patients, 66 depressed elderly outpatients, and 25 age- and sex-matched healthy elderly control subjects. Seventeen percent of the demented patients and 4% of the normal subjects were DST nonsuppressors, compared to 38% of the total depressed group. The postdexamethasone plasma cortisol levels of the dementia group fell between those of the normal and the depressed subjects. In addition, demented patients had postdexamethasone cortisol levels significantly lower than those of depressed patients with high Hamilton depression scores. Older subjects in all diagnostic categories, including normal subjects, had higher postdexamethasone plasma cortisol levels.
MeSH Terms
- Aged
- Aging
- Ambulatory Care
- Dementia
- Depressive Disorder
- Dexamethasone
- Diagnosis, Differential
- Female
- Humans
- Hydrocortisone
- Male
- Middle Aged
- Psychiatric Status Rating Scales
Hematologic data and results of diagnostic tests were compared between aged (greater than or equal to 20 years old) and young (less than or equal to 5 years old) horses to identify hematologic and metabolic changes associated with aging. Initial data were obtained from 8 aged and 6 young mares (group 1). Similar data were collected from a second group of aged (3 mares and 3 geldings) and young (1 mare and 5 geldings) horses (group 2). Dexamethasone suppression tests (DST) and necropsies were performed on 6 additional mares and mare 8 from group 1 (group 3). Complete blood counts and serum biochemical profiles were compared between young and aged horses of groups 1 and 2. Mean corpuscular volume was higher (P less than 0.05) in aged horses. Oral glucose tolerance and insulin response to orally administered glucose were measured in 13 aged horses (groups 1 and 2) and 6 young mares of group 1. In group 1, plasma ascorbic acid values were lower (P less than 0.05) in aged horses than in young horses maintained under the same conditions and feeding regimens. An apparent age-related hyperinsulinemic response to orally administered glucose identified in group-1 mares was probably a result of a high occurrence of subclinical hypophyseal and/or thyroid adenomas. Of 13 aged horses necropsied (groups 2 and 3), 10 had hypophyseal and/or thyroid adenomas that, in group 2, were consistently associated (P less than 0.05) with hyperinsulinemic responses to orally administered glucose. All horses in groups 2 and 3 were given a 24-hour DST.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Animals
- Blood Cell Count
- Blood Chemical Analysis
- Dexamethasone
- Female
- Glucose Tolerance Test
- Hematologic Tests
- Horses
- Hydrocortisone
- Insulin
- Male
The abnormal performance of the DST in depressive illness has been shown to be one of the most reproducible findings in biological psychiatry. Initial claims of its very high diagnostic specificity for the diagnosis of endogenous depression have not been substantiated: an abnormal response appears to reflect a biological dysfunction that cuts across the clinically established boundaries of psychiatric nosology. This lack of diagnostic utility does not reduce its prognostic value and abnormal DST response may indicate or reflect a versatile component in psychiatric disturbance and could serve therefore to predict or monitor the effects of physical and psychological intervention. Contributory factors to abnormal DST response are explored: factors such as stress, nutrition and age are reviewed and discussed. Concepts of biogenetic (neurohumoral) and psychological (psychodynamic and psychosocial) vulnerability and initiation/promotion are invoked and an integrated hypothesis is suggested: emotional strain provokes neurohumoral and neuroendocrine changes; these changes lead to vegetative disturbances including loss of appetite and weight with subsequent nutritional deficiencies that promote/reverse their neurohumoral and neuroendocrine changes. The role of 5-hydroxytryptamine is emphasized. Supportive evidence for aspects of this hypothesis is provided including animal studies and studies of the clinical and biological correlates of abnormal DST response.
MeSH Terms
- Adrenal Cortex Hormones
- Adrenocorticotropic Hormone
- Aging
- Animals
- Antidepressive Agents
- Corticotropin-Releasing Hormone
- Depressive Disorder
- Dexamethasone
- Electroconvulsive Therapy
- Humans
- Hypothalamo-Hypophyseal System
- Macaca mulatta
- Male
- Mental Disorders
- Mice
- Models, Theoretical
- Nutritional Physiological Phenomena
- Pituitary-Adrenal System
- Prognosis
- Rats
- Receptors, Serotonin
- Serotonin
- Social Dominance
- Stress, Physiological
- Tryptophan
Eleven-beta-hydroxylase activity was measured before and after acute adrenocorticotrophic hormone (ACTH) stimulation in 28 controls, 25 depressed Dexamethasone Suppression Test (DST) suppressors, 13 DST nonsuppressor patients, and 8 patients with Cushing's syndrome to investigate changes in states of cortisol hypersecretion. Eleven-beta-hydroxylase activity was equivalent among groups both before and after stimulation. Such 11-beta-hydroxylase stability, however, resulted in higher cortisol and 11-deoxycortisol poststimulation levels in both depressed DST nonsuppressors and Cushing's patients than in controls. Basal 11-beta-hydroxylase activity is positively correlated and 11-deoxycortisol is negatively correlated with age in controls and DST suppressors, but not in the patients tested with evidence of cortisol hypersecretion. These findings suggest that in vivo basal 11-beta-hydroxylase activity rises gradually with age, but does not rise after acute administration of exogenous ACTH. The age relationship is lost in states of cortisol hypersecretion, but the lack of response to acute exogenous ACTH is not affected.
MeSH Terms
- Adrenocorticotropic Hormone
- Adult
- Aging
- Cortodoxone
- Cushing Syndrome
- Depressive Disorder
- Dexamethasone
- Female
- Humans
- Hydrocortisone
- Male
- Middle Aged
- Sex Factors
- Steroid 11-beta-Hydroxylase
- Steroid Hydroxylases
A study of 60 healthy volunteers ranging from 19-88 yr of age found nonsuppression rare (5%) and confirmed that the dexamethasone suppression test (DST) of the reactivity of the hypophyseal-pituitary-adrenal axis to negative feedback inhibition requires 0800 h plasma dexamethasone (DEX) levels in excess of 220 ng/dl. All of the subjects with inadequate DEX levels (N = 3) were older than 50 yr of age as were the nonsuppressors (N = 3); two of the three nonsuppressors had inadequate DEX concentrations. Thus, DST may be more often invalid in elders than in younger adults because of inadequate plasma dexamethasone (DEX) concentration, indicating that plasma DEX levels should be assayed concomitantly with DST in elders.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Dexamethasone
- Female
- Humans
- Hydrocortisone
- Male
- Middle Aged
- Reference Values
The dexamethasone suppression test (DST) is commonly accepted as an indicator of hypothalamus-pituitary-adrenal (HPA) axis functioning in clinical practice. In this study, DST was carried out in a geriatric population composed of patients with dementia of Alzheimer type (DAT), stroke and age-matched controls. The stress state of the subjects was also functionally assessed by the Symptoms Rating Test (SRT). The results disclosed no significant differences in basal cortisol levels in the three groups. A positive correlation between age and log-transformed basal cortisol levels was found in the entire population as well as in each group. After dexamethasone administration, 20% of controls, 49% of DAT patients, and 48% of stroke patients were non-suppressors. At 8.00 a.m. and 11.00 p.m. after dexamethasone, cortisol levels were significantly lower (p less than 0.02) in controls than in pathological groups. A significant positive correlation between age and symptoms of depression and anxiety was found. One-third of stroke patients showing lesions in the right hemisphere were non-suppressors, and presented mostly subcortical infarcts, while 1/4 of them had depressive disorders. This study demonstrated a progressive increase in basal cortisol levels and depressive symptoms with age, a poor diagnostic value of DST in age-related pathological conditions such as DAT and stroke, and the role of these cerebral pathologies in amplifying the neuroendocrine dysregulation due to the ageing process itself. DST is a useful biological marker for disclosing the vulnerability of the ageing brain, but it has no diagnostic value.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Biomarkers
- Brain
- Cerebrovascular Disorders
- Dexamethasone
- Female
- Humans
- Hydrocortisone
- Hypothalamo-Hypophyseal System
- Male
- Neurosecretory Systems
- Pituitary-Adrenal System