Telomeres in a Life-Span Perspective: A New "Psychobiomarker"?

ABSTRACT— In order to more fully understand associations between psychological stress and health, it is helpful for researchers to identify "psychobiomarkers," or biological measures that are regulated in part by psychological function and that predict longevity. Telomere length appears to be such a measure. Telomeres, the protective caps at the tips of chromosomes, shorten with age, and this shortening predicts disease and longevity. Leukocyte telomere length may be best viewed through a life-span approach, as it reflects in part the cumulative number of cell divisions that have occurred and the long-term biochemical environment. Recently, a critical mass of studies demonstrated that telomeres appear to shorten with chronic stress, although the mechanisms are unknown. This paper reviews what appear to be malleable determinants of rate of telomere attrition, focusing on early life chronic stressors and metabolic adversity (poor nutrition during development, and obesity). The next generation of research will benefit from experimental and longitudinal models integrating genetic variation, social environments, life experience, and health behaviors.     

Chronic social stress during adolescence in mice alters fat distribution in late life: prevention by antidepressant treatment

Obesity and visceral fat accumulation are key features of the metabolic syndrome that represents one of the main health problems in western societies due to its neurovascular and cardiovascular complications. Epidemiological studies have identified chronic stress exposure as an important risk factor for the development of obesity and metabolic syndrome, but also psychiatric diseases, especially affective disorders. However, it is still unclear if chronic stress has merely transient or potentially lasting effects on body composition. Here, we investigated the effects of chronic social stress during the adolescent period on body fat composition in mice one year after the cessation of the stressor. We found that stress exposure during the adolescent period decreases subcutaneous fat content, without change in visceral fat, and consequently increases the visceral fat/subcutaneous fat ratio in adulthood. Further, we demonstrated that treatment with a selective serotonin reuptake inhibitor (paroxetine) during stress exposure prevented later effects on body fat distribution. These results from a recently validated chronic stress paradigm in mice provide evidence that stressful experiences during adolescence can alter body fat distribution in adulthood, thereby possibly contributing to an increased risk for metabolic diseases. Antidepressant treatment disrupted this effect underlining the link between the stress hormone system, metabolic homeostasis and affective disorders.     

Diabetes mellitus as a model of psychosomatic and somatopsychic interrelationships

The article reviews research on the problem of interrelationship between different physical and psychosocial factors in type 1 diabetes mellitus (DM1). The authors consider methodological principles of health-related quality of life (HRQoL) assessment in DM1 patients and stress the need for an integrated biopsychosocial approach to the management of the disease. DM1 is a chronic metabolic disease with an absolute requirement for insulin replacement therapy. The stress-inducing nature of DM1 is associated with its unexpected and dramatic manifestation in juvenile years, life-threatening nature of severe hypo-/hyperglycaemias and long-term complications, with the burden of diabetes self-management, threat of work disability, employment and career problems etc. These features of DM1 increase the likelihood of the development of anxiety and depressive disorders, which, in turn, may negatively influence the course of diabetes and in particular, diabetes self-care. This necessitates early diagnosis of emotional and behavioral disturbances in DM1 using self-report instruments as well as clinical assessment. Evidence suggests that active problem-focused coping behavior and adequate social support promote adherence to diabetes regimes and may act as a buffer against negative effects of the disease on HRQoL in DM1 patients. The core element in the HRQoL structure is personal disease picture (as opposed by objective clinical picture)--the cognitive-affective-behavioral complex reflecting the patient's personal perception of the disease. Examination of the personal disease picture and attitude towards the ailment in DM1 patients may help to improve understanding of the mechanisms of poor adjustment. Problems in disease adjustment can be detected also by diabetes-specific HRQoL assessment. The measures of HRQoL can be applied as screening instruments useful in increasing the effectiveness of patient-provider interactions and diabetes care.     

The Impact of Race on Metabolic Disease Risk Factors in Women With and Without Posttraumatic Stress Disorder

The literature on PTSD and metabolic disease risk factors has been limited by lacking investigation of the potential influence of commonly comorbid disorders and the role of race. In this study data were provided by a sample of 134 women (63 PTSD and 71 without PTSD). Separate sets of models examining associations of psychiatric disorder classifications with metabolic disease risk factors were used. Each model included race (African American or Caucasian), psychiatric disorder, and their interaction. There was an interaction of race and PTSD on body mass index, abdominal obesity, and triglycerides. While PTSD was not generally associated with deleterious health effects in African American participants, PTSD was related to worse metabolic disease risk factors in Caucasians. MDD was associated with metabolic disease risk factors, but there were no interactions with race. Results support the importance of race in the relationship between PTSD and metabolic disease risk factors. Future research would benefit from analysis of cultural factors to explain how race might influence metabolic disease risk factors in PTSD.     

Stress and eating: Definitions,findings, explanations,and implications

As high stress has become ubiquitous in modern society, so too has the prevalence of overweight and obesity, leading many to question whether these changes are related. Does stress affect eating? In this article, we summarize research investigating associations between stress and eating and describe the mechanisms that may explain such associations. Our review indicates that regardless of how stress and eating are operationalized, manipulated, or analyzed, and regardless of sample characteristics, associations of stress with eating behavior are observed quite consistently, with some variability due to individual differences. There is also evidence that the link between stress and eating involves both biological and behavioral processes. We discuss the possible longer term implications of stress–eating associations for weight gain, weight stigma, and subsequent health, and we identify specific methodological and conceptual advances needed to improve further research and application.     

Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety

Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.     

Just world beliefs, causal beliefs, and acquaintance: Associations with stigma toward eating disorders and obesity

The current study investigated the relationship between just world beliefs and stigmatizing attitudes toward eating disorders and obesity. Further, the associations between stigma and causal beliefs, and between stigma and acquaintance with these conditions, were examined. Participants (n = 447) read four vignettes describing an individual with anorexia nervosa, bulimia nervosa, binge eating disorder, or obesity. After each vignette, participants completed questionnaires assessing stigmatizing attitudes, just world beliefs, causal beliefs, and acquaintance with the condition depicted in the vignette. Stronger just world beliefs were associated with greater stigma toward all three eating disorders, as well as obesity (rs ranging from −.11 to −.18). More stigmatizing attitudes were associated with greater attribution of individual responsibility for the development of the disorder. However, participants with personal experience or who knew someone with the depicted problem did not have lower stigma scores than those who did not. The current study suggests that justification ideologies such as just world beliefs and controllability beliefs may underlie the stigmatization of eating disorders and obesity. These findings provide support for stigma reduction efforts aimed at targeting justification ideologies and altering causal beliefs.     

Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of obesity

Obesity has negative health consequences related to fat distribution, particularly the central or visceral accumulation of fat. The major complications associated with visceral obesity, termed the "Metabolic Syndrome of Obesity," or "Syndrome X," are type II diabetes, hypertension, and dyslipidemia. As with certain mood disorders, the syndrome may be a consequence of neuroendocrine perturbations typically associated with chronic stress. Our work with bonnet macaque monkeys provides an animal model for the relationship between early stress, behavioral and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and Syndrome X. During their infant's first half-year, mothers face a variable foraging demand (VFD), in which ample food varies unpredictably in the difficulty of its acquisition, and the offspring show persistent abnormalities in systems known to modulate stress and affective regulation. Early work on the bonnet macaque noted the emergence of a sample of spontaneously obese subjects as they matured. Using the VFD model, the current study showed that there was a clear relationship between early cerebrospinal fluid corticotropin-releasing factor levels and subsequently measured body mass index, supporting the hypotheses regarding the interactive roles of early experience and HPA axis dysregulation in the ontogeny of both metabolic and mood disorders.     

代谢综合征发病机制研究进展

随着经济的发展和人们生活水平的提高以及生活方式的改变,代谢综合征（metabolic syndrome,MS）的患病率逐年上升。代谢综合征是一种涉及多种代谢异常、与心血管病紧密联系的疾病状态。肥胖或超重、糖调节异常或糖尿病、高血压和高血脂是MS的重要组成元素。代谢综合征一直是人们关注的热点,但截止目前确切机制仍不明确。主要围绕肥胖与胰岛素抵抗展开研究,特别是在脂毒性和脂肪分泌因子的调控以及各种炎性因子的影响方面取得了一些进展。     

神经影像视角下的肥胖脑机制研究

肥胖作为一种全球性流行病,与许多慢性非传染性疾病密切相关。本文主要从脑功能和脑结构层面对现有肥胖研究做系统梳理。脑功能上,个体在加工食物线索时奖赏环路的过度激活、认知控制环路的活动缺失构成了肥胖的易感因子。脑结构上,全脑灰质体积、白质纤维束完整性和整体弥散水平的降低,从不同的影像层面提供了肥胖的神经解剖证据。未来研究可以从纵向研究的开展、干预措施的扩展和多模态脑成像数据的整合等方面展开。     

Chronic stress accelerates atherosclerosis in the apolipoprotein E deficient mouse

Conventional cardiovascular risk factors such as cholesterol and blood pressure do not account fully for variation in coronary heart disease suggesting the involvement of additional mechanisms. We have examined the effects of a chronic psychological stress protocol on the development of atherosclerosis in the apolipoprotein E knockout mouse. We observed a 3-fold increase in staining for atheroma accompanied by a 10-fold increase in corticosterone concentrations in mice stressed for 12 weeks. These data suggest that chronic mild stress can induce or accelerate the development of atherosclerosis.     

Chronic stress, cognitive functioning and mental health

This review aims to discuss the evidence supporting the link between chronic stress, cognitive function and mental health. Over the years, the associations between these concepts have been investigated in different populations. This review summarizes the findings that have emerged from older populations as well as from populations suffering from pathological aging, namely Mild Cognitive Impairment and Alzheimer's Disease. Although older adults are an interesting population to study in terms of chronic stress, other stress-related diseases can occur throughout the lifespan. The second section covers some of these stress-related diseases that have recently received a great deal of attention, namely burnout, depression, and post-traumatic stress disorder. Given that chronic stress contributes to the development of certain pathologies by accelerating and/or exacerbating pre-existing vulnerabilities that vary from one individual to the other, the final section summarizes data obtained on potential variables contributing to the association between chronic stress and cognition.     

代谢综合征：动脉粥样硬化危险因素的聚集

代谢综合征是动脉粥样硬化危险因素的聚集状态,包括肥胖、高血压、血糖异常、血脂紊乱等,共同的病理基础是肥胖和胰岛素抵抗。高胰岛素血症、脂肪因子、高血糖、血脂异常和高血压导致内皮细胞损伤和血管炎症,促进动脉粥样硬化发展。提高对代谢综合征的认识有助于从整体观念出发防治肥胖带来的相关疾病。     

Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners

While no single factor accounts for the significant increases in overweight and obesity that have emerged during the past several decades, evidence now suggests that sugars, in general, and sugar-sweetened beverages, in particular, may be especially problematic. One response to this concern has been an explosion in the availability and use of noncaloric sweeteners as replacements for sugar. While consumers have been led to believe that such substitutes are healthy, long-term epidemiological data in a number of cohorts have documented increased risk for negative outcomes like type 2 diabetes, heart disease, and stroke among users of artificial sweeteners. Experimental data from animals has provided several plausible mechanisms that could explain this counterintuitive relationship. In particular, my research has demonstrated that artificial sweeteners appear to interfere with basic learned, predictive relations between sweet tastes and post-ingestive consequences such as the delivery of energy. By interfering with these relations, artificial sweeteners inhibit anticipatory responses that normally serve to maintain physiological homeostasis, and over the long term, this interference could result in negative health effects like those seen in the human cohort studies. These data suggest that reducing the consumption of all sweeteners is advisable to promote better health.     

急性心理应激对多囊卵巢综合征患者的影响

为了了解PCOS患者易患抑郁症、肥胖、代谢综合征、心血管疾病、糖尿病的原因。通过对28例PCOS患者和28例体重指数、年龄匹配的健康对照组回应公众演讲压力进行分析,在回应公众演讲压力时,PCOS组和对照组均有比较显著的焦虑程度、ACTH、皮质醇、心率和血压升高（P均〈0．01）;但PCOS患者焦虑程度、ACTH、皮质醇...     

Are Large Physiological Reactions to Acute Psychological Stress Always Bad for Health?

How we react physiologically to stress has long been considered to have implications for our health. There is now persuasive evidence that individuals who show large cardiovascular reactions to stress are at increased risk of developing cardiovascular disease, particularly hypertension. By implication, low reactivity is protective or benign. However, there is recent evidence that low reactivity may predict elevated risk for a range of adverse health outcomes, such as depression, obesity, poor self-reported health and compromised immunity. In addition, low cortisol and cardiovascular reactivity may be a characteristic of individuals with addictions to tobacco and alcohol, as well as those at risk of addiction and those who relapse from abstinence. Our ideas about reactivity may have to be revised in the light of such findings.     

Stress and inflammatory disease: widening roles for serotonin and substance P

Serotonin has been implicated in mediating the hypothalamo-pituitary-adrenal (HPA) axis response to stress and is an important therapeutic target for a number of psychiatric disorders including depression. The neurokinin substance P has been shown to inhibit stress-induced HPA axis activity and we have demonstrated that endogenous substance P is able to reduce the duration of the HPA axis response to stress suggesting an important role in the termination of the stress response. This may be important in controlling the transition from acute to chronic stress and substance P has recently attracted attention as a potential antidepressant.In addition to these central effects, serotonin and substance P are considered to be pro-inflammatory agents. Despite being implicated in mediating inflammation there have been few studies investigating the effects of manipulations of serotonergic or substance P systems on chronic inflammatory disease. Treatment of rats with adjuvant-induced arthritis(AA), a model of chronic inflammatory stress, with a substance P antagonist specific for the NK1 receptor subtype resulted in a reduction in hind paw inflammation suggesting substance P may influence inflammation. We have noted that depletion of whole body serotonin and selective central depletion of serotonin results in a decrease in the severity of inflammation in rats with adjuvant arthritis. Furthermore, treatment with a selective serotonin reuptake inhibitor results in an earlier onset and increased severity of inflammation in adjuvant arthritis, confirming a pro-inflammatory role for serotonin. Serotonin is also present in the immune tissues and concentrations in the spleen fall following the development of inflammation in adjuvant arthritis. Concentrations of serotonin are significantly higher in normal female spleen than in males, and this may underlie the greater predisposition of females to certain autoimmune diseases.There is increasing evidence of a role for transmitters such as serotonin and substance P,both centrally and peripherally, in mediating a wide variety of inflammatory and psychiatric disorders. A better understanding of the mechanisms of action of these transmitters and the development of suitable drugs targeting specific receptor subtypes has great potential to impact on clinical practice in the near future. The purpose of this review is to consider the separate roles of serotonin and substance P in relation to HPA axis stress responses, in the context of a model of chronic inflammatory disease, highlighting novel directions of current research for each of these transmitters.     

Review of Family Relational Stress and Pediatric Asthma: The Value of Biopsychosocial Systemic Models

Asthma is the most common chronic disease in children. Despite dramatic advances in pharmacological treatments, asthma remains a leading public health problem, especially in socially disadvantaged minority populations. Some experts believe that this health gap is due to the failure to address the impact of stress on the disease. Asthma is a complex disease that is influenced by multilevel factors, but the nature of these factors and their interrelations are not well understood. This paper aims to integrate social, psychological, and biological literatures on relations between family/parental stress and pediatric asthma, and to illustrate the utility of multilevel systemic models for guiding treatment and stimulating future research. We used electronic database searches and conducted an integrated analysis of selected epidemiological, longitudinal, and empirical studies. Evidence is substantial for the effects of family/parental stress on asthma mediated by both disease management and psychobiological stress pathways. However, integrative models containing specific pathways are scarce. We present two multilevel models, with supporting data, as potential prototypes for other such models. We conclude that these multilevel systems models may be of substantial heuristic value in organizing investigations of, and clinical approaches to, the complex social–biological aspects of family stress in pediatric asthma. However, additional systemic models are needed, and the models presented herein could serve as prototypes for model development.     

Long-term relations of personality and health: dynamisms, mechanisms, tropisms

There is now little doubt that individuals who are well-adjusted, socially stable, and well-integrated into their communities are at significantly lower risk for disease and premature mortality than those who are more unstable, impulsive, isolated, and alienated. The reasons for these associations, however, are complex and the pathways insufficiently studied. This article employs a life-span data set to explore how childhood personality relates to health-related growth and development (dynamisms), patterns of reactions and health behaviors (mechanisms), and movements toward and away from suitable environments (tropisms). Illustrations from the 7-decade Terman longitudinal data reveal important areas in which previous, cross-sectional research has misinterpreted associations between personality and health. In particular, Sociability has been overrated as a life-span health risk factor, Conscientiousness has been underrated, and Neuroticism has been confused. Without sufficient attention to the processes underlying the associations between personality and health, significant suboptimal allocations of intervention resources result.