A Social Neuroscience Perspective on Stress and Health

Psychological stress is a major risk factor for the development and progression of a number of diseases, including cardiovascular disease, cancer, arthritis, and major depression. A growing body of research suggests that long term, stress‐induced activation of the sympathetic nervous system (SNS) and the hypothalamic‐pituitary‐adrenal (HPA) axis may lead to increases in inflammation, which is known to play a key role in the pathophysiology of a variety of diseases. Furthermore, the burgeoning fields of social neuroscience and health neuroscience have begun to identify the neurocognitive mechanisms by which stress may lead to these physiological changes. Here we review the literature examining the neurocognitive correlates of stress‐induced SNS, HPA, and inflammatory responses. Specifically, we summarize the results of neuroimaging studies that have examined the neural correlates of stress‐related increases in SNS, HPA, and inflammatory activity. A set of neural systems involved in threat processing, safety processing, and social cognition are suggested as key contributors to stress‐related changes in physiology. We conclude by offering suggestions for future research in the exciting new field of health neuroscience.     

Enhancing effects of acute psychosocial stress on priming of non-declarative memory in healthy young adults

Social stress affects cognitive processes in general, and memory performance in particular. However, the direction of these effects has not been clearly established, as it depends on several factors. Our aim was to determine the impact of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity to psychosocial stress on short-term non-declarative memory and declarative memory performance. Fifty-two young participants (18 men, 34 women) were subjected to the Trier Social Stress Task (TSST) and a control condition in a crossover design. Implicit memory was assessed by a priming test, and explicit memory was assessed by the Rey Auditory Verbal Learning Test (RAVLT). The TSST provoked greater salivary cortisol and salivary alpha-amylase (sAA) responses than the control task. Men had a higher cortisol response to stress than women, but no sex differences were found for sAA release. Stress was associated with an enhancement of priming but did not affect declarative memory. Additionally, the enhancement on the priming test was higher in those whose sAA levels increased more in response to stress (r(48)?=?0.339, p?=?0.018). Our results confirm an effect of acute stress on priming, and that this effect is related to SNS activity. In addition, they suggest a different relationship between stress biomarkers and the different memory systems.     

Evidence for discrete profiles of children’s physiological activity across three neurobiological system and their transitions over time

The conceptualization of stress‐responsive physiological systems as operating in an integrated manner is evident in several theoretical models of cross‐system functioning. However, limited empirical research has modeled the complexity of multisystem activity. Moreover few studies have explored developmentally regulated changes in multisystem activity during early childhood when plasticity is particularly pronounced. The current study used latent profile analysis (LPA) to evaluate multisystem activity during fall and spring of children's transition to kindergarten in three biological systems: the parasympathetic nervous system (PNS), sympathetic nervous system (SNS), and hypothalamic pituitary adrenal (HPA) axis. Latent transition analysis (LTA) was then used to examine the stability of profile classification across time. Across both timepoints, three distinct profiles of multisystem activity emerged. One profile was characterized by heightened HPA axis activity (HPA Axis Responders), a second profile was characterized by moderate, typically adaptive patterns across the PNS, SNS, and HPA axis (Active Copers/Mobilizers), and a third profile was characterized by heightened baseline activity, particularly in the PNS and SNS (Anticipatory Arousal/ANS Responders). LTA of fall‐to‐spring profile classifications indicated higher probabilities that children remained in the same profile over time compared to probabilities of profile changes, suggesting stability in certain patterns of cross‐system responsivity. Patterns of profile stability and change were associated with socioemotional outcomes at the end of the school year. Findings highlight the utility of LPA and LTA to detect meaningful patterns of complex multisystem physiological activity across three systems and their associations with early adjustment during an important developmental transition.     

Cortisol reactivity and regulation associated with shame responding in early childhood

The purpose of this study was to characterize cortisol response and regulation associated with shame responding in early childhood and to examine how general the relation between shame and cortisol is. It was predicted that children responding to task failure with shame would show a larger and more prolonged cortisol response than other children. Participants were 214 children (124 boys, 90 girls) ranging from 3.7 to 4.5 years of age (M = 4.14 years, SD = 0.24). Shame responding was assessed from children's emotion-expressive behavior in response to failing 6 performance tasks, 2 preceding (initial) and 4 following (subsequent) assessment of hypothalamic-pituitary-adrenal axis activation. Cortisol response and regulation associated with failure were assessed from saliva sampled before and 15, 20, 25, 30, and 40 min following the first of the 2 initial failures. For boys and for some girls, high initial shame was associated with greater cortisol reactivity and slower regulation of the cortisol response. For boys, high initial shame and relatively slow regulation of the associated cortisol response predicted subsequent shame responding occurring after recovery of the cortisol response. For girls, high initial shame, but not cortisol response, predicted subsequent shame responding. (PsycINFO Database Record (c) 2008 APA, all rights reserved).     

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.     

Hypothalamo-Pituitary-Adrenocortical Regulation Following Lesions of the Central Nucleus of the Amygdala

Previous reports indicate that the central nucleus of the amygdala (CeA) stimulates adrenocorticotropin and corticosterone secretion, suggesting a role for this region in central hypothalamo-pituitary-adrenocortical (HPA) stress regulation. To evaluate this hypothesis, this study assessed the impact of CeA lesion on the response of hypophysiotrophic paraventricular nucleus (PVN) neurons to acute restraint and chronic unpredictable stress exposure. In contrast to previous reports, CeA lesions did not affect corticosterone or ACTH secretion induced by acute stress. Acute restraint increased PVN corticotropin releasing hormone (CRH) mRNA expression, increased the number of parvocellular PVN neurons expressing the co-secretagogue arginine vasopressin (AVP), and induced cFOS mRNA expression in the parvocellular PVN. However, there was no additional effect of CeA lesion on any measure of PVN activation. Chronic unpredictable stress exposure induced long-term activation of the HPA axis, noted by thymic involution, adrenal hypertrophy and increased PVN CRH mRNA expression. Stress-induced changes in thymus and adrenal weights were not affected by CeA lesion. Further, CeA lesion rats did not differ from controls in post-stress CRH mRNA expression. However, basal CRH mRNA expression was increased in the PVN of CeA rats, suggesting that the CeA plays a role in long-term inhibition of the PVN. The results of these studies are not consistent with the hypothesis that the CeA is necessary for stress-induced pituitary-adrenocortical activation. Rather, this region may play a stressor-specific modulatory role in regulation of HPA function.     

The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome

The hypothalamo-pituitary-adrenal (HPA) axis plays a major role in the regulation of responses to stress. Human stress-related disorders such as chronic fatigue syndrome (CFS), fibromyalgia syndrome (FMS), chronic pelvic pain and post-traumatic stress disorder are characterized by alterations in HPA axis activity. However, the role of the HPA axis alterations in these stress-related disorders is not clear. Most studies have shown that the HPA axis is underactive in the stress-related disorders, but contradictory results have also been reported, which may be due to the patients selected for the study, the methods used for the investigation of the HPA axis, the stage of the syndrome when the tests have been done and the interpretation of the results. There is no structural abnormality in the endocrine organs which comprise the HPA axis, thus it seems that hypocortisolemia found in the patients with stress-related disorder is functional. It may be also an adaptive response of the body to chronic stress. In this review, tests used in the assessment of HPA axis function and the HPA axis alterations found in CFS and FMS are discussed in detail.     

慢性军事应激致军人海马形态、认知功能和应对方式的变化

通过对572名连续4~16个月高强度军事训练的军人进行SCL-90测评, 研究慢性军事应激条件下军人海马形态、认知、心理特质和特质应对方式的变化特征。将其中l7例焦虑因子分≥3分者(焦虑或伴焦虑)设为研究组(A), 并以匹配法设对照组(B)。检测两组军人血皮质醇, 并用MRI观察海马形态、检测简单和复杂认知作业功能、以STAI测评状态-特质焦虑及以CCSQ测评应对方式, 探讨两组对应变化。研究结果显示：(1)血皮质醇：A、B组均高于正常水平, 有差异显著, A组显著高于B组。(2)海马形态：A组与B组MRI海马形态标准化后, A组海马形态显著萎缩, 与B组相比有显著性差异, 但各组每个同体的左右两侧之间相比无显著性差异。(3)认知作业功能：A组简单认知作业成绩与B组无显著差异, 但复杂认知作业成绩与B组相比有显著性差异。(4)状态-特质焦虑：A组的状态焦虑、特质焦虑分别与B组和常模比较均有显著变化, B组与常模相比状态焦虑变化显著, 特质焦虑变化不显著。(5)应对方式：A组积极应对方式平均值低于B组和常模并有显著性差异, B组高于常模; A组消极应对方式平均值高于B组和常模且有非常显著性差异, B组与常模无显著改变。结论 在慢性军事应激条件下, 特质焦虑个体的海马形态出现双侧萎缩, 复杂认知功能下降, 更易发生状态焦虑, 行为取向表现出积极应对方式降低、消极应对方式增加。     

The central nucleus of the amygdala; a conduit for modulation of HPA axis responses to an immune challenge?

Physical stressors such as infection, inflammation and tissue injury elicit activation of the hypothalamic-pituitary-adrenal (HPA) axis. This response has significant implications for both immune and central nervous system function. Investigations in rats into the neural substrates responsible for HPA axis activation to an immune challenge have predominantly utilized an experimental paradigm involving the acute administration of the pro-inflammatory cytokine interleukin- 1β (IL-1β). It is well recognized that medial parvocellular corticotrophin-releasing factor cells of the paraventricular nucleus (mPVN CRF) are critical in generating HPA axis responses to an immune challenge but little is known about how peripheral immune signals can activate and/or modulate the mPVN CRF cells. Studies that have examined the afferent control of the mPVN CRF cell response to systemic IL-1β have centred largely on the inputs from brainstem catecholamine cells. However, other regulatory neuronal populations also merit attention and one such region is a component of the limbic system, the central nucleus of the amygdala (CeA). A large number of CeA cells are recruited following systemic IL-lβ administration and there is a significant body of work indicating that the CeA can influence HPA axis function. However, the contribution of the CeA to HPA axis responses to an immune challenge is only just beginning to be addressed. This review examines three aspects of HPA axis control by systemic IL-1β: (i) whether the CeA has a role in generating HPA axis responses to systemic IL-1β, (ii) the identity of the neural connections between the CeA and mPVN CRF cells that might be important to HPA axis responses and(iii) the mechanisms by which systemic IL-Iβ triggers the recruitment of CeA cells.     

Differentiating the impact of episodic and chronic stressors on hypothalamic-pituitary-adrenocortical axis regulation in young women.

OBJECTIVE: The goal of this study was to examine the impact of episodic stress and chronic interpersonal stress on indices of HPA regulation. To explore the potential downstream consequences of altered HPA dynamics, the authors also assessed indicators of metabolic control and systemic inflammation. DESIGN: One hundred four medically healthy women between the ages of 15 and 19 participated. Following an in-depth interview of life stress, a sample of blood was drawn through antecubital venipuncture. Over the course of the next 2 days, participants gathered salivary cortisol samples. MAIN OUTCOME MEASURES: Cortisol morning response, cortisol daily output, glucocorticoid receptor (GR) mRNA, C-reactive protein (CRP), insulin, and glucose. RESULTS: The simple presence of episodic stress or chronic interpersonal stress was not reliably associated with cortisol output, GR mRNA, insulin, or glucose. When women were exposed to an episodic stressor in the midst of chronic stress they showed increased cortisol output and reduced expression of GR mRNA. By contrast, when women had low levels of chronic stress, episodic events were associated with decreased cortisol output and increased GR mRNA. Episodic and chronic stress also interacted to predict CRP, but not insulin or glucose. CONCLUSIONS: The impact of episodic stress is accentuated in the midst of chronic interpersonal stress and diminished in its absence. Simultaneous exposure to episodic and chronic stress may create wear and tear on the body, whereas exposure to episodic stress in the context of a supportive environment may toughen the body, protecting it against subsequent stressors.     

Mindfulness Meditation for Symptom Reduction in Fibromyalgia: Psychophysiological Correlates

Objectives Fibromyalgia, a chronic pain syndrome, is often accompanied by psychological distress and increased basal sympathetic tone. In a previous report it was shown that mindfulness-based stress-reduction (MBSR) reduced depressive symptoms in patients with fibromyalgia with gains maintained at two months follow-up (Sephton et al., Arthr Rheum 57:77–85, 2007). This second study explores the effects of MBSR on basal sympathetic (SNS) activation among women with fibromyalgia. Methods Participants (n = 24) responded to a television news appearance, newspaper, and radio advertisements. Effects on anxiety, depressive symptoms, and SNS activation measures were tested before and after MBSR using a within-subjects design. Results The MBSR treatment significantly reduced basal electrodermal (skin conductance level; SCL) activity (t = 3.298, p = .005) and SCL activity during meditation (t = 4.389, p = .001), consistent with reduced SNS activation. Conclusions In this small sample, basal SNS activity was reduced following MBSR treatment. Future studies should assess how MBSR may help reduce negative psychological symptoms and attenuate SNS activation in fibromyalgia. Further clarification of psychological and physiological responses associated with fibromyalgia may lead to more beneficial treatment.     

背景应激对静息态下大脑自发神经活动的影响

本研究试图探究背景应激对应激相关大脑自发神经活动的影响。使用日常应激水平作为背景应激的量化指标。同时，使用静息态fMRI技术，采集了个体在静息态下的大脑自发神经活动，并使用局部一致性（ReHo）作为指标。结果发现，背景应激越高的个体，右侧海马（扩展到丘脑和脑干）静息态下局部一致性水平越高。结果提示，经历了高背景应激的个体会表现出边缘系统脑区的自发神经活动的持续活跃状态。     

Involvement and role of the hypothalamo-pituitary-adrenal (HPA) stress axis in animal models of chronic pain and inflammation

Hypothalamo-pituitary-adrenal (HPA) axis changes have been reported in several disease states, including major depressive disorder, rheumatoid arthritis, multiple sclerosis and various other conditions associated with chronic pain. These observations suggest that stress and the HPA axis may play important roles in the pathology of these diseases. In order to contribute to a better understanding of the role that chronic stress may play in human pathology, this review article explores the involvement of the HPA axis in those animal models of chronic pain and inflammation that entail persistent rather than intermittent stress.     

If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans

The notion that chronic stress fosters disease by activating the hypothalamic-pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed that much of the variability is attributable to stressor and person features. Timing is an especially critical element, as hormonal activity is elevated at stressor onset but reduces as time passes. Stressors that threaten physical integrity, involve trauma, and are uncontrollable elicit a high, flat diurnal profile of cortisol secretion. Finally, HPA activity is shaped by a person's response to the situation; it increases with subjective distress but is lower in persons with posttraumatic stress disorder.     

Maternal separation in early life impairs tumor immunity in adulthood in the F344 rat

Neonatal stress alters the hypothalamic-pituitary-adrenal (HPA) axis in rodents, such that, when these animals are exposed to stress as adults they hypersecrete corticosterone. Given that glucocorticoids are immunosuppressive, we examined the impact of maternal separation on HPA axis reactivity, natural killer (NK) cytotoxicity, and tumor growth in Fischer 344 rats following chronic restraint stress in adulthood. Pups underwent a chronic stress protocol whereby they were separated from their dams for 3 h on postnatal days 1-21. In adulthood, corticosterone responses were assessed following exposure to chronic (6 days for 10 h) restraint stress. Rats allocated to the chronic stress condition were inoculated with MADB106 tumor cells on day 4 of the restraint protocol. Blood was assessed for NK cytotoxicity on the final day of the chronic restraint protocol, and tumor colonization was assessed 3 weeks thereafter. Maternal separation impaired developmental weight gain (P < 0.05), depressed NK cytotoxicity (P < 0.05), and increased tumor colonization in the presence of chronic restraint stress in adulthood (P < 0.00 l). These findings occurred independently of circulating plasma corticosterone as only adult stress exposure potentiated corticosterone responses (P < 0.05). Our findings indicate that maternal separation and chronic stress can impair NK cytotoxicity and hence tumor immunity, but these effects are not directly mediated by perturbations in HPA axis function.     

Evidence that baroreflex feedback influences long-term incidental visual memory in men

Sympathetic nervous system (SNS) activity at the time of acquisition is associated with human memory. However, rather than SNS activity per se, it may be afferent baroreflex feedback that is responsible for this effect. A pharmacological design was employed to unload (SNP, sodium nitro-prusside) and load (norepinephrine) baroreceptors. In addition to two placebo periods, epinephrine and esmolol (a peripherally acting beta1-blocker) served as control conditions for altered cardiac perception. During drug infusion blood pressure, heart rate, and perception of heartbeat were tested. Twenty-four healthy men were participated. The participants viewed emotional slides while their electromyographic eye blink responses to random noise bursts were measured (affective startle modulation paradigm) to determine potential drug impact on emotional processing. Subjects were not informed that memory testing would take place after 4 weeks. Drugs did not impact startle, thus indicating unbiased emotional processing at the time of acquisition. Norepinephrine had no effect on heartbeat perception, but improved (p = .002) recognition memory. SNP (p = .0001) increased heartbeat perception but impaired (p = .038) recognition memory. Epinephrine, on the other hand, increased heartbeat perception (p = .0001) yet did not impair but partially improve memory (effect on high arousing pictures only: p = .05). Heartbeat perception in the placebo condition did not correlate with recognition memory (p's > .5). We suggest that baroreflex unloading, with subsequent feedback activation of the SNS, impairs long-term incidental visual recognition memory in humans while baroreflex loading enhances it. Further, we propose that these memory effects are neither secondary to cardiac sensations that accompany SNS activation nor to altered emotional picture processing at the time of acquisition.     

Wives' and Husbands' Cortisol Reactivity to Proximal and Distal Dimensions of Couple Conflict

Poor marital quality has been linked repeatedly to spouses' health problems, with alterations to physiological stress response systems, such as the hypothalamic‐pituitary‐adrenocortical (HPA) axis, as one putative mechanism. This study assessed wives' and husbands' HPA axis (i.e., cortisol) reactivity to marital criticism during laboratory‐based conflict discussions, in the context of marital aggression experienced during the previous year. Ninety‐five couples provided one saliva sample prior to—and three samples following—a triadic family conflict discussion involving their teenage child. Marital criticism during the conflict discussion was related to heightened HPA reactivity for husbands only. For wives, an interaction emerged between criticism during the conflict and previous‐year marital aggression: only those wives who had experienced high levels of marital aggression demonstrated a positive association between criticism and cortisol output. Husbands thus appeared to be more physiologically reactive to the in‐the‐moment critical behaviors, whereas wives' responses to proximal conflict were related to previous and perhaps more chronic experiences of marital aggression. These findings shed light on ways in which within‐couple processes during family conflicts involving children contribute to individual physiological functioning, enhancing our understanding of the role of family relationships in physical health outcomes.     

Adolescent Personality: Associations With Basal,Awakening, and Stress‐Induced Cortisol Responses

The purpose of the present study was to investigate the associations between personality facets and hypothalamic‐pituitary‐adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress‐induced HPA‐axis activation. We hypothesized that other characteristics of HPA‐axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress‐induced HPA‐axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress‐induced cortisol were not related to personality. Possibly due to its more trait‐like nature, basal cortisol seems more informative than stress‐induced cortisol when investigating trait‐like characteristics such as personality facets.