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[应激反应研究:焦虑、皮质醇和脱氢表雄酮的作用]

[Study of the stress response: role of anxiety, cortisol and DHEAs].

作者信息

Boudarene M, Legros J J, Timsit-Berthier M

机构信息

Bat G, N 266, Cité Djurdjura, Ville Nouvelle, Tizi Ouzou 15010, Algérie, France.

出版信息

Encephale. 2002 Mar-Apr;28(2):139-46.

PMID:11972140
Abstract

AIM OF THE STUDY

Several studies have exhibited the psychological processes that are implied in the stress response and have shown, according to Selye's research, the participation of the hypothalamic-pituitary-adrenal axis and the major role of cortisol. The possible action of another adrenal steroïd, dehydroepiandrosterone (DHEA), is increasingly documented. The beneficial effect of the latter and his antistress role would be related to an antagonistic action to that of cortisol. The aim of our study was, first to assess biological and psychological aspects of the stress response, then to define the relationships that exist between these two processes.

POPULATION AND METHODOLOGY

40 subjects (21 women) aged 42 +/- 12 years, who consulted within a clinic of stress (CITES Prevert, Liege, Belgium) were studied. They all felt stressed but, according to DSM IV, were without mental disorders and drug free when examined. Subjects were asked to accomplish simple cognitive tasks: 1 - to distinguish two different auditory stimulations. The first one was a high-pitched sound of 1 470 Hz, which was presented unfrequently (20%). The second one, a low frequency tone of 800 Hz, was presented more frequently (80%). The interval between both stimuli was 1 s. The subject had to press a button when the rare stimulus was recognized. 2 - to extinguish a light after a warning tone of 64 dB, 50 ms and 1 000 Hz. The light, which followed one second later the tone, consisted of a series of flashes of 18 c/s that the subject had to stop by pressing a button. The purpose of this second procedure was that the subject was warned and had to prepare and anticipate the most rapid response. After that, subjects were submitted to self-evaluation psychological tests. The impact of psychosocial factors was assessed by Amiel-Lebigre life events questionnaire. Personality features and emotional response (state anxiety, related to experimental situation) were assessed by Spielberger inventory (STAI: State and Trait Anxiety Inventory). Psychological tests are practised immediately after experimental situation. Cortisol and DHEAs (dehydroepiandrosterone sulfate) were measured in blood samples taken before (t1) and after (t2) the experimental test. Cortisol was measured by radio-immunology and expressed as ng/ml of plasma. DHEAs was measured by radio-immunoassay and expressed as g/liter of plasma.

RESULTS AND DISCUSSION

The majority of subjects displayed high scores of trait anxiety (37 subjects had a score>42) and life events impact (35 subjects had a score>200). These data confirmed that the subjects were fragile and were obviously stressed. In response to the cognitive tasks, that constituted for each subject a new event with which it was necessary to cope, 25 subjects exhibited high level of state anxiety (score>42) and an increase of cortisol plasmatic concentrations occurred solely in 11 persons. Ten among them were in the group of subjects which displayed a score of state anxiety>42 (p=0,0223, Chi square). Base on these data three types of stress response were identified: 1 - the experimental situation was experienced without anxiety ( psychological silence ) and without any increase in cortisol level ( biological silence ). There was no stress and these subjects were, despite their vulnerability, close to a normal health state . 2 - high emotional reaction (high level of state anxiety) was observed. This response reveals a psychological vulnerability that can be considered as the expression of a consecutive psychological distress induced by a threatening experimental situation. There were no biological manifestations ( biological silence ). 3 - high state anxiety and increased plasma cortisol levels were observed. The corresponding subjects were obviously more vulnerable.

CONCLUSION

These results allow us to propose that the emergence of state anxiety is the first stress response and the primary protest . Up to a certain level, a plateau level, anxiety remains stable. Then, nature of the stress response changes and takes a biological aspect. Increased of cortisol plasma levels, the secondary protest , is observed and gives evidence of an intensified and sustained stress response. Such a gradual phenomenon is particularly reported in elevated psychological distress which is associated with loss of control. It is important to note that identical scores of state anxiety (Mann Whitney test) were observed in anxious subjects with or without rise of plasma cortisol levels. DHEAs was also implied in the stress response. The enhancement of plasma levels of DHEAs were dependent on cortisol, as shown by the close correlation between both hormones (r=0,433, p=0,0033, Spearman test). The hypothesis of an antagonism between these two hormones is based on the fact that DHEAs opposes the action of cortisol and exerts a true anticortisol effect. This antagonism might be related to a competition in their synthesis and release by the adrenal gland. In the present case, high level of anxiety (state and trait) was associated with an increase of cortisol, while low level (of anxiety) was related to an exclusive rise of DHEAs. Intermediate anxious score was observed in subjects who showed increases of both cortisol and DHEAs (p=0,0225, Kruskall Wallis test). Furthermore, a close relationship (negative correlation: Spearman test), was observed between increases in DHEAS and scores of state anxiety (r=- 0,382, p=0,06) and trait anxiety (r=- 0,0097, p=0,527). This means that the worriness and the underlying anxious ruminations and negative anticipations, which characterize trait anxiety, were less important in subjects who increased plasma DHEAs levels. In addition, emotional tension and uneasiness, which accompanies state anxiety, were also less marked. There are no studies reporting a relation between DHEA(s) and state or trait anxiety. Nevertheless, many authors have proposed a beneficial action of DHEA on the feeling of well-being. This beneficial role could be related to a double action of DHEA: a direct effect provided by its transformation into sexual hormones, an indirect one mediated by its competition with cortisol, of which the synthesis and consequently the activity decrease.

摘要

研究目的

多项研究揭示了应激反应中所涉及的心理过程,并且根据塞利的研究表明,下丘脑 - 垂体 - 肾上腺轴参与其中,皮质醇起主要作用。另一种肾上腺类固醇脱氢表雄酮(DHEA)的可能作用也有越来越多的文献记载。后者的有益作用及其抗应激作用可能与其对皮质醇作用的拮抗作用有关。我们研究的目的,首先是评估应激反应的生物学和心理学方面,然后确定这两个过程之间存在的关系。

研究对象与方法

对40名年龄在42±12岁的受试者(21名女性)进行了研究,这些受试者在一家应激诊所(比利时列日的CITES普雷韦尔诊所)咨询。他们都感到有压力,但根据《精神疾病诊断与统计手册》第四版,在检查时没有精神障碍且未服用药物。受试者被要求完成简单的认知任务:1 - 区分两种不同的听觉刺激。第一种是1470赫兹的高音,出现频率较低(20%)。第二种是800赫兹的低频音,出现频率较高(80%)。两种刺激之间的间隔为1秒。当识别出罕见刺激时,受试者必须按下按钮。2 - 在64分贝、50毫秒和1000赫兹的警告音后熄灭灯光。灯光在声音之后一秒出现,由一系列每秒18次的闪光组成,受试者必须通过按下按钮来停止。第二个程序的目的是让受试者得到警告,并必须准备并预期做出最快反应。之后,受试者接受自我评估心理测试。通过阿米尔 - 勒比格雷生活事件问卷评估社会心理因素的影响。通过斯皮尔伯格量表(STAI:状态 - 特质焦虑量表)评估人格特征和情绪反应(与实验情境相关的状态焦虑)。心理测试在实验情境后立即进行。在实验测试前(t1)和后(t2)采集的血样中测量皮质醇和硫酸脱氢表雄酮(DHEAs)。皮质醇通过放射免疫法测量,以血浆中纳克/毫升表示。DHEAs通过放射免疫测定法测量,以血浆中微克/升表示。

结果与讨论

大多数受试者表现出高特质焦虑得分(37名受试者得分>42)和生活事件影响得分(35名受试者得分>200)。这些数据证实受试者较为脆弱且明显处于压力之下。对于每个受试者而言,认知任务构成了一个需要应对的新事件,25名受试者表现出高水平的状态焦虑(得分>42),并且仅11人血浆皮质醇浓度升高。其中10人在状态焦虑得分>42的受试者组中(p = 0.0223,卡方检验)。基于这些数据,确定了三种应激反应类型:1 - 实验情境中无焦虑体验(心理平静)且皮质醇水平无任何升高(生物学平静)。没有应激反应,这些受试者尽管易受影响,但接近正常健康状态。2 - 观察到高情绪反应(高水平的状态焦虑)。这种反应揭示了一种心理脆弱性,可被视为由具有威胁性的实验情境引起的连续心理困扰的表现。没有生物学表现(生物学平静)。3 - 观察到高状态焦虑和血浆皮质醇水平升高。相应受试者明显更易受影响。

结论

这些结果使我们能够提出,状态焦虑的出现是第一种应激反应和主要抗议形式。在达到一定水平,即平稳期之前,焦虑保持稳定。然后,应激反应的性质发生变化并呈现生物学方面。观察到血浆皮质醇水平升高,即第二种抗议形式,这证明了应激反应的加剧和持续。这种逐渐变化现象在与失控相关的高度心理困扰中尤为明显。需要注意的是,在血浆皮质醇水平升高或未升高的焦虑受试者中观察到相同的状态焦虑得分(曼 - 惠特尼检验)。DHEAs也参与了应激反应。血浆DHEAs水平的升高依赖于皮质醇,这两种激素之间的密切相关性表明了这一点(r = 0.433,p = 0.0033,斯皮尔曼检验)。这两种激素之间存在拮抗作用的假设基于这样一个事实,即DHEAs对抗皮质醇的作用并发挥真正的抗皮质醇效应。这种拮抗作用可能与它们在肾上腺中的合成和释放竞争有关。在本研究中,高焦虑水平(状态和特质)与皮质醇增加相关,而低焦虑水平与DHEAs单独升高相关。在皮质醇和DHEAs均升高的受试者中观察到中等焦虑得分(p = 0.0225,克鲁斯卡尔 - 沃利斯检验)。此外,观察到DHEAS升高与状态焦虑得分(r = - 0.382,p = 0.06)和特质焦虑得分(r = - 0.0097,p = 0.527)之间存在密切关系(负相关:斯皮尔曼检验)。这意味着在血浆DHEAs水平升高的受试者中,作为特质焦虑特征的担忧以及潜在的焦虑沉思和消极预期不太重要。此外,伴随状态焦虑出现的情绪紧张和不安也不太明显。没有研究报道DHEA(s)与状态或特质焦虑之间的关系。然而,许多作者提出DHEA对幸福感有有益作用。这种有益作用可能与DHEA的双重作用有关:一种是由其转化为性激素产生的直接作用,另一种是由其与皮质醇竞争介导的间接作用,皮质醇的合成及活性因此降低。

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