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。     

创伤后应激障碍患者的HPA轴功能变化的时间序列特征

已知创伤后应激障碍(posttraumatic stress disorder, PTSD)患者表现出HPA轴(hypothalamic-pituitary- adrenocortical axis)功能异常, 而皮质醇是反映PTSD患者HPA轴功能的重要生物标记。近期的研究结果提示, PTSD患者的皮质醇水平变化可能有明显的时间序列特征, 即应激事件发生后先升高, 后下降至正常水平之下。这一特征受到生物标记的时间特性, 患者病程, 应激源类型和强度, 伴生疾病等因素的干扰和掩蔽。未来研究应进一步采用长期追踪设计, 控制干扰因素的影响, 结合急性应激和慢性应激生物标记来综合验证PTSD患者皮质醇水平变化的时间序列特征|并利用该特征预测PTSD的发生、发展, 以便及时进行干预|考虑皮质醇的代谢、拮抗等机制, 结合多种生物标记综合评估、诊断PTSD患者的HPA轴功能活性。     

急性心理性应激诱发的神经内分泌反应及其影响因素

急性心理性应激源分别通过下丘脑-脑垂体-肾上腺轴(hypothalamus–pituitary–adrenal axis,HPAA)和交感神经-肾上腺髓质轴(sympathetic-adrenal medulla axis)诱发神经内分泌反应。唾液皮质醇被认为是检测急性心理性应激所诱发的HPA轴反应的稳定指标。以特里尔社会应激测试(Trier Social Stress Test,TSST)及其变式作为应激源, 以HPA轴的反应作为应激指标, 影响个体在急性心理性应激情境中发生特异性神经内分泌反应的因素主要包括人口统计学、环境和应激频率三大方面, 未来应加强急性心理性应激所诱发的神经内分泌反应的纵向研究。     

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。     

经前期综合征女性的HPA轴功能失调：一项基于皮质醇水平的元分析

HPA轴(Hypothalamic-Pituitary-Adrenal,HPA)功能失调是压力相关情绪障碍形成或者恶化的决定因素。为系统评价基线状态和面临环境挑战时经前期综合征(PremenstrualSyndrome,PMS)女性基于皮质醇水平的HPA轴功能失调,对1990年以来的32项研究(总样本量N=1280)进行了定量整合,以期为女性经前期综合征的病因和干预提供参考。结果发现：在基线研究中, PMS女性黄体期的皮质醇含量显著低于普通女性,且受到皮质醇测量时间的调节作用;PMS女性卵泡期的皮质醇含量与普通女性无显著差异。环境挑战研究的结果与基线研究类似,PMS女性黄体期的皮质醇含量显著低于普通女性,但卵泡期的皮质醇含量与普通女性无显著差异。该结果提示压力内分泌轴的持久改变和面对压力时的HPA轴反应迟钝是PMS产生的可能病理机制。未来研究应关注应激调节策略来改善PMS的不良反应。     

应激影响脑老化的相关学说与机制

应激是机体受到各种内外环境因素刺激时的适应性反应,当反应持续时间过久或长期处于激活状态,则会对机体产生不良影响。目前认为,老化与糖皮质激素的过量分泌所致大脑相关区域的损伤相关,这些区域不仅参与认知与情绪,而且与下丘脑-垂体-肾上腺轴控制的其他活动相关。除此之外,皮质醇基础水平的差异性、皮质醇在脑内的可用性、糖皮质激素受体的失衡及大脑本身的易损性、回弹性等都是应激影响脑老化的参与因素。本文将对应激所致正常或非正常老化过程的相关影响机制与学说进行综述。     

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。     

神经及内分泌系统对社会支持缓冲应激的调节机制

应激是生活中不可避免的事件,过度应激也是许多疾病发生的诱因。应激会引起一系列生理反应,包括激活自主神经系统及神经内分泌系统,表现为自主神经系统(ANS)和下丘脑–垂体–肾上腺(HPA)活动的增加。社会支持通过改变或抑制应激相关脑区的活动,缓冲了应激引起的ANS和HPA轴活动,使机体快速恢复到应激前水平,避免应激引起的内稳定失衡对机体的伤害。     

负性情绪对分泌型免疫球蛋白A的影响及其神经内分泌机制

本研究考察负性情绪条件下个体粘膜免疫功能与其交感神经系统、下丘脑-垂体-肾上腺皮质轴反应之间的关系。采用负性情绪图片为情绪应激材料,分析观看图片对个体心率、收缩压、舒张压、唾液皮质醇浓度和分泌型免疫球蛋白A(SIgA)浓度、分泌率的影响。结果发现:(1)负性情绪图片可以诱发被试明显的负性情绪,使其收缩压、舒张压、唾液皮质醇水平明显上升,SIgA水平下降;(2)相关分析表明,舒张压和心率变化趋势与被试的SIgA水平呈负相关;(3)实验说明由负性情绪图片诱发的情绪造成了SIgA下降,且与交感神经系统的变化有关。     

特里尔社会应激测验对儿童皮质醇分泌的影响

研究以32名小学儿童（平均年龄10.47岁,男生16人）为被试,采用唾液皮质醇为应激测验的客观指标、以被试主观紧张度为主观指标,考察特里尔社会应激测验对中国儿童皮质醇分泌的影响。结果表明：（1）社会应激测验任务引发儿童皮质醇浓度和主观紧张度的显著上升,任务后的恢复期皮质醇浓度和主观紧张度能够恢复到任务前的水平。（2）社会应激测验任务引发的男生皮质醇水平变化显著高于女生,但是引发的主观紧张度水平变化不存在显著性别差异。社会应激测验中文修订版能够有效引发儿童的压力应激变化,可以用其开展儿童社会应激的相关研究。     

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.     

Individual differences in cortisol responses to fear and frustration during middle childhood

The purpose of this study was to examine individual differences in the activation and regulation of the hypothalamic-pituitary-adrenal (HPA) axis in prepubertal children after exposure to two different stress modalities and to evaluate the utility of an individual differences approach to the examination of HPA axis functioning. After a 30-min controlled baseline period, 73 7-year-olds (40 boys and 33 girls) were randomly assigned to a validity check condition or one of two experimental tasks designed to elicit fear or frustration. This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples were collected, including 12 poststress samples at 5-min intervals. There was a significant stress modality effect, with children exposed to the fear condition reaching peak cortisol levels at 25 min poststress and those exposed to the frustration condition reaching peak levels at 45 min poststress. There was no difference in peak cortisol levels between the stress modalities. Individual variability across conditions was significant, with participants reaching peak levels as early as 10 min poststress and as late as 60 min poststress. Our data suggest that analysis of individual curves prior to making group-level comparisons may improve the explanatory power of HPA axis behavior models.     

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.     

Diurnal patterns of salivary cortisol and DHEA in adolescent anorexia nervosa

Although there is well-documented evidence for hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis function in anorexia nervosa (AN), there has been little research into secretory patterns of salivary cortisol and dehydroepiandrosterone (DHEA) in this condition. The cortisol awakening response (CAR), a prominent and discrete feature of the cortisol cycle, has not been extensively explored in adolescent AN. Saliva samples were collected at awakening, 30?min and 12 h post-awakening on two consecutive weekdays from eight female adolescents with clinically diagnosed AN and 41 healthy control (HC) age-matched females. Adolescent AN patients had greater salivary cortisol and DHEA concentrations than HC girls at all points. Increased hormone secretion was unrelated to body mass index. However, despite hypersecretion of both hormones, the circadian pattern including the CAR paralleled that of the HC group. Findings from this preliminary study confirm dysregulation of HPA axis function in adolescent AN as evidenced by hypersecretion of both cortisol and DHEA, which share the common secretagogue adrenocorticotropic hormone. However, the parallel diurnal profiles for AN and HC participants, including the CAR, may indicate hypersecretion per se rather than differential regulation of the diurnal pattern of these two adrenal steroids in AN.     

Effortful control and parenting: Associations with HPA axis reactivity in early childhood

While activation of the hypothalamic‐pituitary‐adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent–child interactions, may play an important role in shaping the developing HPA system; however, the association of parent affect may be moderated by child factors, especially children's emerging self‐regulatory skills. We therefore tested the relationship between parent affectivity and 160 preschoolers’ cortisol reactivity during a laboratory visit, examining children's effortful control (EC) as a moderator. Greater parent negative affectivity was related to greater initial and increasing cortisol over time, but only when children were low in EC. Higher parent positive affectivity was related to a higher baseline cortisol for children with low EC and lower baseline cortisol for children with high EC. Results indicate that children's EC moderates the extent to which parent affect shapes stress reactive systems in early childhood.     

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.     

Measurement and meaning of salivary cortisol: a focus on health and disease in children

Measurement of salivary cortisol can provide important information about hypothalamic-pituitary-adrenal (HPA) axis activity under normal conditions and in response to stress. However, there are many variables relating to the measurement of cortisol in saliva which may introduce error and therefore may render difficult the comparison and interpretation of data between, and within, laboratories. This review addresses the effects of gender, age, time and location of sampling, units of measurement, assay conditions and compliance with the protocol, all of which have the potential to impact upon the precision, accuracy and reliability of salivary cortisol measurements in the literature. Some of these factors are applicable to both adults and children, but the measurement of salivary cortisol in children introduces aspects of unique variability which demand special attention. The specific focus of this review is upon the somewhat neglected area of methodological variability of salivary cortisol measurement in children. In addition to these methodological issues, the review highlights the use of salivary cortisol measurements to provide information about HPA axis dysfunction associated with psycho- and patho-physiological conditions in children. Novel applications for salivary cortisol measurements in future research into HPA axis activity in children are also discussed.