Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children

The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to elicit fear (N = 33) or frustration (N = 32), or a validity check condition (N = 8). This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples for cortisol analysis were collected including 12 post-stress samples at 5-min intervals. Reactive and proactive aggression levels were assessed via the teacher-completed Aggression Behavior Teacher Checklist (Dodge and Coie, J Pers Soc Psychol, 53(6), 1146–1158, 1987). Reactive aggression significantly predicted total and peak post-stress cortisol regardless of stress modality. Proactive aggression was not a predictor of any cortisol index. Examination of pure reactive, proactive, combined, or non-aggressive children indicated that reactive aggressive children had higher cortisol reactivity than proactive and non-aggressive children. Our data suggest that while an overactive HPA-axis response to stress is associated with reactive aggression, stress induced HPA-axis variability does not seem to be related to proactive aggression.     

Working memory performance after acute exposure to the cold pressor stress in healthy volunteers

Effects of acute stress exposure on learning and memory have been frequently studied in both animals and humans. However, only a few studies have focused specifically on working memory performance and the available data are equivocal. The present study examined working memory performance during the Sternberg item recognition task after exposure to a predominantly adrenergic stressor. Twenty four healthy subjects were randomly assigned to a stress group or a control group. The stress group was exposed to the cold pressor stress test (CPS; i.e. insertion of the dominant hand into ice water for 60s), while 37 °C warm water was used with the control group. Twenty minutes after the stress exposure, working memory performance was tested with the Sternberg item recognition task with three levels of cognitive load. Sympathetic nervous system and hypothalamic pituitary adrenocortical (HPA) axis activation during CPS, were assessed by measuring heart rate and salivary cortisol before and during (heart rate) or 30 min after (cortisol) the stress procedure. Exposure to the CPS test was associated with a significant increase in heart rate but no increase in salivary cortisol. Participants exposed to the stress procedure showed significantly shorter reaction times during trials with higher cognitive load but tended to show higher false alarm rates than control subjects. The present results indicate that exposure to CPS can be associated with signs of both enhanced and impaired working memory performance. The observed behavioral pattern might represent a form of streamlined information processing advantageous in a threatening situation.     

儿童版特里尔社会应激测试对儿童唾液皮质醇、唾液α-淀粉酶和情绪的影响

研究以150名五、六年级的学生为被试,考察儿童版特里尔社会应激测试（TSST-C）对儿童客观生理反应（唾液皮质醇和唾液α-淀粉酶）和主观情绪反应的影响。结果发现,TSST-C引起了儿童显著的应激反应,包括皮质醇和唾液α-淀粉酶水平的升高,以及主观消极情绪（如焦虑和紧张）的增加,这表明TSST-C在中国儿童中的适用情况良好,能够有效诱发儿童的应激反应。同时,研究也发现,皮质醇反应和唾液α-淀粉酶反应不存在相关,生理反应和情绪反应之间也不存在相关。     

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.     

The cortisol awakening response and the big five personality dimensions

The present study investigated the association between the big five personality dimensions and the cortisol awakening response (CAR), a physiological parameter reflective of HPA axis activity. One hundred and seven participants completed the big five inventory (BFI; John, Donahue, & Kentle, 1991) and collected salivary cortisol samples at 0, 30, and 60 min after awakening on a weekday morning. The cortisol awakening response under the curve (CARauc) and the cortisol awakening response with respect to increase (CARi) were used as outcome variables in the statistical analyses. Hierarchical linear regression analyses were conducted using the data of 92 participants. Gender and age were included as covariates in block one of the regressions, followed by the personality dimensions in block two. Extraversion emerged as a significant predictor of CARauc. No other personality dimensions were significantly predictive of CARauc or CARi. Interestingly, gender emerged as the strongest predictor in the CARauc, with females exhibiting greater cortisol release across the awakening period than males. Our results suggest that extraversion and gender may be particularly important variables to consider in the regulation of the HPA axis.     

Circadian activity of the hypothalamic-pituitary-adrenal axis is differentially affected in the rat chronic mild stress model of depression

The altered activity of the hypothalamic-pituitary-adrenal (HPA) axis is often observed in stress-related disorders. According to the literature, about 60% of patients with major depressive disorder elicit high levels of cortisol. It is still unclear why high cortisol levels are not observed in all patients. In this study, we used the chronic mild stress (CMS) rat model of depression, which is based on continuous exposure to unpredictable stressors, to track longitudinal changes in HPA function using fecal corticosterone metabolites (FCM) as a read out. The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Our results show (1) a disturbance in diurnal corticosterone rhythm measured as fluctuations of the diurnal FCM peak, (2) differences in corticosterone levels between stress-susceptible and stress-resilient animals, (3) recovery of diurnal corticosterone rhythm after 8 weeks of CMS, and (4) alterations in sensitivity to dexamethasone in negative feedback regulation of corticosterone secretion during the time course of CMS. Thus, a disruption of HPA axis circadian rhythmicity coincides with the initial state in the development of depression-like behavior. This chronobiological abnormality, as well as the hypersecretion of corticosterone, is state, rather than trait, dependent.     

Effects of stress and sex on acquisition and consolidation of human fear conditioning

We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after acquisition and retention of fear conditioning. Results showed two effects of endogenous cortisol. Post-acquisition cortisol correlated with fear acquisition in male but not female participants. In addition, post-acquisition cortisol correlated with consolidation of fear but only in those participants with high cortisol levels. We conclude that in the short term, a robust and sexually dimorphic relationship exists between fear learning and stress hormone levels. For those participants whose fear learning is accompanied by high stress hormone levels, a long-term relationship exists between cortisol release and memory consolidation. These short-term and long-term effects may relate to the differential involvement of mineralocorticoid and glucocorticoid receptor subtypes, respectively. The findings have implications for understanding the role of stress, sex, and hormones in different stages of fear learning and memory.     

重复性急性应激对攻击行为的影响及调控机制

关于急性应激对攻击行为的影响, 现有研究多集中于单次急性应激情境下。然而, 相比单次急性应激, 对重复暴露于同一应激源的研究更能反映人们在现实生活中经历的应激事件。与单次应激不同, 重复性急性应激与应激适应有关, 能够节省资源, 具有很强的进化和适应意义, 但目前关于重复性急性应激对攻击行为的影响却知之甚少。鉴于此, 研究运用事件电位相关技术、鼻喷催产素和催产素受体基因型分析方法, 探讨重复性急性应激对攻击行为的影响及内部机制, 并进一步探讨通过内部和外部调控重复性急性应激反应后攻击行为的变化。     

Physiological Correlates of Choice‐Induced Dissonance: An Exploration of HPA‐Axis Responses

Choice can produce a negatively arousing cognitive conflict (called dissonance), which is thought to motivate the chooser to spread their preferences for the relevant options (called Spreading of Alternatives, or SA). The current work aimed to determine the relationship between HPA‐axis activity and both choice‐induced dissonance and its reduction (i.e. SA) among individuals with varying cultural backgrounds. European–Americans and Asians made a choice between two equally attractive CDs either in the presence of a cue indicative of social eyes (i.e. public‐choice condition) or in the absence thereof (i.e. private‐choice condition). As predicted, European–Americans and Asians showed a reliable SA primarily in the private and public choice conditions, respectively. Importantly, a sharp decline of salivary cortisol was observed over the span of 30 min, and, moreover, this decline was reliably predicted by the magnitude of SA regardless of either culture or the choice being private vs. public. These results suggest that although choice‐induced dissonance is too weak to elicit an HPA‐axis stress response, SA is associated with variability in the decline of salivary cortisol during the laboratory task. Copyright © 2015 John Wiley & Sons, Ltd.     

皮质醇日常节律与儿童问题行为及心理社会因素的关系

HPA轴(下丘脑?垂体?肾上腺皮质轴, hypothalamic-pituitary-adrenal cortex axis)是人体应对压力的重要神经内分泌系统, 其终产物皮质醇常作为测量压力的生物学指标。目前的研究多通过皮质醇日常节律表示静息状态下HPA轴的活动, 而日常节律因其较高的稳定性和可靠性成为儿童生理健康评估的最佳指标。儿童期迅速发育的神经内分泌系统与儿童的行为相互作用, 并受到多种心理社会因素的影响。以往研究主要关注皮质醇日常节律与儿童问题行为及心理社会因素的关系, 未来研究应讨论逆境条件下影响儿童成长的危险性因素和保护性因素, 并探索环境对儿童行为影响可能存在的内分泌机制。     

Stress impairs acquisition of delay eyeblink conditioning in men and women

In rodents stress impairs delay as well as trace eyelid conditioning in females, but enhances it in males. The present study tested the effects of acute psychosocial stress exposure on classical delay eyeblink conditioning in healthy men and women. In a between subject design, participants were exposed to psychosocial stress using the Trier Social Stress Test (TSST) or a control condition which was followed by a delay eyeblink classical conditioning procedure. Stress exposure led to a significant increase in salivary cortisol and impaired acquisition of conditioned eyeblink responses (CRs). This was evident by a later first CR and an overall lower CR rate of the stress group. The stress-induced acquisition impairment was observed in both women and men. Subjects failing to show a stress-induced cortisol increase (cortisol non-responder) were not impaired in acquisition. Our findings indicate that acute stress, possibly via activation of the hypothalamus–pituitary–adrenal (HPA) axis, reduces the ability to acquire a simple conditioned motor response in humans.     

Peer Victimization and Aggression: Moderation by Individual Differences in Salivary Cortiol and Alpha-Amylase

This research examined whether variations in salivary measures of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (alpha amylase [sAA]) contribute to individual differences in the association between peer victimization and aggression. Children (N = 132; M age = 9.46 years, SD = 0.33) completed a measure of peer victimization, teachers rated children’s aggression, and children’s saliva was collected prior to, and following, participation in a laboratory-based peer-oriented social challenge task. Children rated their level of frustration at the end of the task. Results revealed that victimization interacted with cortisol and sAA measured in anticipation of the task to predict aggression; the victimization × cortisol contribution to aggression was partly mediated by children’s self-reported frustration level. Victimization also was associated with heightened frustration in girls with high task-related sAA reactivity. Task-related sAA reactivity was associated with heightened aggression, but only for girls. These findings suggest that associations between peer victimization and aggression are moderated by variation in the activity of the major components of the psychobiology of stress; results are discussed in relation to theoretical models of individual differences in biological sensitivity to context.     

The effects of exposure to an acute naturalistic stressor on working memory, state anxiety and salivary cortisol concentrations

Exposure to an acute naturalistic stressor induces both psychological and physiological changes in humans. The two studies reported here explored the impact of exposure to an acute naturalistic stressor on state anxiety, working memory and HPA axis activation (salivary cortisol). In both experiments, ten healthy male participants were exposed to an acute naturalistic stressor, helicopter underwater evacuation training (HUET), and their physiological and behavioural responses before (first study) and after (second study) the stressor were compared to ten non-stressed controls. The results of both experiments showed that working memory performance was preserved during anticipation of an acute stressor, but impairments were observed immediately after stress exposure. Participants reported significantly higher state anxiety levels during anticipation and following stress exposure, whereas significant elevations in cortisol levels were only observed 25 min post exposure to stress, but not before or immediately after stress exposure. The results of both experiments demonstrated a dissociation between behavioural and biochemical measures and provided evidence for a dissociation of the effects of stress on cognitive and physiological measures depending on the time of testing, with cognitive impairments most evident following stress exposure.     

应激神经成像的研究述评

HPA轴(hypothalamic-pituitary-adrenal cortex axis)是人体的重要内分泌应激系统, 大脑通过控制HPA轴活动影响机体在应激情境中皮质醇(cortisol)的分泌, 同时皮质醇分泌对大脑也具有负反馈作用, 影响着大脑边缘系统的重塑; 海马、杏仁核、前额叶皮层和脑干都参与了应激反应中的皮质醇调节; 未来研究要进一步对应激源细化分类, 并且试图找到适合事件相关电位技术的社会心理性应激实验范式。     

Repeated measurement of salivary cortisol within and across days among shy young adults

Temperamental shyness emerges early in childhood and remains relatively stable throughout development and has been associated with high and low levels of the stress hormone cortisol. Studies examining the relation between shyness and cortisol have been limited because they have traditionally collected only one measure of cortisol on a single day in the laboratory, restricting the reliability and diurnal profile of the measure in the participant’s everyday environment. We collected 15 saliva samples across three separate days (i.e., upon waking, +60 min post-waking, +8 h post-waking, +10 h post-waking, and bedtime) in a sample of healthy young adults selected for high and low shyness in order to characterize a portion of the diurnal cortisol rhythm. Overall, shy individuals demonstrated relatively lower cortisol across the day and across multiple mornings than non-shy adults. Higher self-reported social anxiety across multiple measures was also related to lower total cortisol levels across all participants. The present study replicates and extends our previous findings of low salivary cortisol measured in the laboratory in shy adults to repeated measurement in their everyday environments.     

人类应激内分泌轴功能状态的测量

HPA轴(下丘脑?垂体?肾上腺皮质轴, hypothalamic-pituitary-adrenal cortex axis)是人类重要的应激内分泌轴, 静息与应激条件下HPA轴的机能障碍能引发应激相关疾病, 而HPA轴机能障碍的表现和原因并不明确。皮质醇作为HPA轴的终端产物能直接反映HPA轴活动, 唾液皮质醇优于其他生物样本皮质醇的特性使其成为测量HPA轴活动的最优指标, 因此寻找到合适的唾液皮质醇标识来反映静息与应激条件下的HPA轴调节变化, 能促进理解HPA轴机能障碍与疾病间的神经内分泌通路。近来研究常用的是以皮质醇觉醒反应(cortisol -awakening response, CAR)与特里尔社会应激测试(Trier social stress test, TSST)来分别表示静息与应激条件下的HPA轴活动。未来研究将结合应激反应的生理、心理指标, 进一步考察HPA轴调节的脑网络, 为应激反应提供脑-神经内分泌通路的生物基础。     

Gender differences in cardiovascular and hypothalamic-pituitary-adrenal axis responses to psychological stress in healthy older adult men and women

Gender differences in the neuroendocrine and cardiovascular response to psychological stress may contribute to the gender differences in the prevalence of diseases associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity such as cardiovascular disease (CVD), diabetes and hypertension. We measured plasma ACTH, cortisol, heart rate (HR), and blood pressure (BP) responses in 8 men and 8 women (55-75 years) exposed to the Matt Stress Reactivity Protocol (MSRP), a psychological challenge. The MSRP elicited significant increases in HR, systolic-, and diastolic BP, ACTH and cortisol (all p<0.01). Men had significantly greater cortisol and diastolic BP responses compared to women (p<0.05). Additionally, a positive correlation between the ACTH and cortisol responses was only found in the males (r=0.71, p<0.05). There were no group differences in HR, systolic BP, or ACTH responses. We conclude, that among older adults, men respond to psychological stress with greater increases in cortisol, compared to women. This greater activation of the HPA axis could translate into an elevated risk for CVD, diabetes and hypertension and may be related to the higher prevalence of these diseases in males. Gender differences in brain structures and/or cognitive processes may be responsible for these sexually dimorphic stress responses.     

儿童受欺负与急性社会应激中应激反应的关系

研究旨在考察受欺负经历与儿童下丘脑-垂体-肾上腺轴系统应激功能的关系。根据受欺负得分挑选出52名受欺负和未受欺负儿童,考察两类儿童在特里尔社会应激测验(Trier Social Stress Test,TSST)中的皮质醇分泌及主观紧张度的特征差异。结果发现:(1)在TSST中,受欺负者的皮质醇浓度显著高于未受欺负者;(2)两类儿童在TSST中的主观紧张度不存在显著差异。研究结果与慢性应激破坏HPA轴应激功能的过程是从敏化到钝化的理论假说相一致。     

Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function

The search for novel anxiolytics and antidepressants has focused on compounds with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within the central nervous system, conceivably plays an important role in activating the neural sites involved in stress modulation. Deactivation of the HPA axis by glutamatergic neurotransmission modulation may represent a novel therapeutic approach. Accordingly, the acute intravenous effects of the novel metabotropic (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata) undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent measures were the magnitude of the increase of plasma cortisol and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the effects of 6 weeks of chronic oral administration of LY354740 on baseline (postcapture) plasma cortisol and MHPG levels in comparison to the identical measure in untreated controls were assessed. Subjects chronically treated with LY354740 received yohimbine infusions which were compared to yohimbine infusions and saline infusions in non-LY354740-treated subjects. Preliminary evidence supports the view that acute LY354740 infusion resulted in a marked diminution of yohimbine-induced stress response, as manifest by a substantial attenuation of cortisol and MHPG response observed in comparison to the saline-treated yohimbine condition. Chronic oral administration of LY354740 led to postcapture baseline cortisol levels which were markedly reduced (approximately 50 percent) in comparison to untreated control subjects; however, there were no significant parallel differences in MHPG levels. Yohimbine infusions elicited an increase in cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated subjects, in comparison to declines in cortisol values observed following vehicle infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects failed to achieve cortisol levels comparable in range to those of untreated subjects primarily because of their low baseline cortisol levels. In contrast, despite equivalent baselines, yohimbine-induced MHPG values were increased overall in the chronically treated group compared to the saline and yohimbine-alone groups. Thus, LY354740 markedly reduced the acute corticoid and noradrenergic response elicited by yohimbine infusion. Chronic administration of LY354740 appears to present a safe and effective mechanism to markedly down-modulate the HPA axis while retaining noradrenergic responsivity.     

Parent support is less effective in buffering cortisol stress reactivity for adolescents compared to children

The goal of the present study was to investigate developmental differences in the effectiveness of parent support to alleviate hypothalamic‐pituitary‐adrenal (HPA) axis stress responses of children (ages 9–10, N = 40) and adolescents (ages 15–16, N = 41). We experimentally manipulated the provision of parent support during the speech preparation period before a modified Trier Social Stress Test (TSST) and examined its effect on levels of salivary cortisol secreted in response to this laboratory stressor. Analyses revealed a significant interaction of condition and age group such that social support from the parent (versus a stranger) significantly eliminated the cortisol stress response in children, but had no effect on the response among adolescents.