ALTERED HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL REGULATION IN HEALTHY-SUBJECTS AT HIGH FAMILIAL RISK FOR AFFECTIVE-DISORDERS
ALTERED HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL REGULATION IN HEALTHY-SUBJECTS AT HIGH FAMILIAL RISK FOR AFFECTIVE-DISORDERS
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DOI：
10.1159/000127023
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发表时间：
1995-10-01
影响因子：
4.1
通讯作者：
KRIEG, JC
中科院分区：
文献类型：
--
作者：
HOLSBOER, F;LAUER, CJ;KRIEG, JC
下丘脑-垂体-肾上腺皮质（HPA）系统的负反馈控制改变是重性抑郁症的常见实验室体征。它与抑郁发作相吻合，并在精神病理学恢复后部分逆转。反馈控制中的这种HPA干扰可以是由于紧张的生活经历而获得的，并且随着年龄的增长而加剧，或者它可以在涉及微调神经内分泌调节的所有水平上被遗传预定。我们调查了在抑郁症患者中观察到的HPA反馈障碍是否存在于其他健康个体中，这些健康个体因其一级亲属患有情感性疾病而具有精神障碍的高风险，我们使用严格的心理诊断技术筛选了431例连续入院的抑郁症患者，并确定了35个具有一个或多个高风险先证者（HRPs）的家庭。联合地塞米松/人促肾上腺皮质激素释放激素（DEX-CRH）试验的结果表明，地塞米松预处理组（1.5毫克; 23.00小时）HRPs释放更多的皮质醇刺激后，与人CRH（100微克; 15.00小时，第二天）比对照组（CP），但少于一组患者的急性重性抑郁发作（DP）。皮质醇峰值为146.1 +/- 147.7 nmol/l（平均值+/- SD）（HRP），75.3 +/- 47.9 nmol/l（CP）和278.2 +/- 199.2 nmol/l（DP），产生显著性差异（F = 9.66，p < 0.001）组间差异，HRPs与CP和HRPs与DP的值在1%水平上显著（t检验）。促肾上腺皮质激素（ACTH）反应的HRPs没有超过控制水平，这表明随着时间的推移，肾上腺皮质腺已经开发了一种超敏反应，可能继发于长期过度分泌ACTH。线性判别分析确定32%的HRPs显示皮质醇反应模式无法区分的DP。这些和其他数据分析显示，存在HPA反馈障碍在相当数量的受试者的风险为affective illness.Our的研究结果表明，负反馈缺陷在一些健康的先证者的风险为affective disorder是由皮质类固醇受体功能紊乱。在没有当前或以前的精神疾病或环境因素，如特定的生活方式，可能导致我们的受试者的皮质类固醇受体功能的适应性变化，我们的结论是，我们的研究结果最好理解为指示遗传传播的风险因素，可能使这些人容易患情感障碍。
Altered negative feedback control of the hypothalamic-pituitary-adrenocortical (HPA) system is a frequent laboratory sign of major depression. It coincides with depressive episodes and partially reverses after recovery from psychopathology. Such an HPA disturbance in feedback control can be acquired as a result of stressful life experiences and be compounded by age or it can be genetically predetermined at all levels involved in fine-tuned neuroendocrine regulation.Major psychiatric disorders run in families and a high familial load for an affective illness therefore increases an individual's risk of becoming affected. We investigated whether the HPA feedback disturbance observed among patients with depression is present in otherwise healthy individuals who are at high risk for psychiatric disorders because they have a first-degree relative with an affective illness.Using rigid psychodiagnostic techniques, we screened 431 consecutively admitted patients with depression and identified 35 families with one or more high-risk probands (HRPs). The results of a combined dexamethasone/human corticotropin-releasing hormone (DEX-CRH) test showed that the group of dexamethasone-pretreated (1.5 mg; 23.00 h) HRPs released more cortisol after stimulation with human CRH (100 mu g; 15.00 h the next day) than a control group (CPs), but less than a group of patients with an acute major depressive episode (DPs). The peak cortisol values were 146.1 +/- 147.7 nmol/l (mean +/- SD) (HRPs), 75.3 +/- 47.9 nmol/l (CPs) and 278.2 +/- 199.2 nmol/l (DPs), yielding significant (F = 9.66, p < 0.001) group differences, with values for HRPs vs. CPs and HRPs vs. DPs being significant at the 1% level (t test). The adrenocorticotropin (ACTH) responses of the HRPs did not exceed control levels, suggesting that over time the adrenocortical gland had developed a hypersensitivity, possibly secondary to long-term overexposure to ACTH. A linear discriminant analysis identified 32% of the HRPs as showing cortisol response patterns indistinguishable from those of DPs. These and other data analyses revealed the presence of an HPA feedback disturbance in a substantial number of subjects at risk for affective illness.Our findings suggest that the negative feedback defect in a number of healthy probands at risk for affective disorder is caused by a disturbed corticosteroid receptor function. In the absence of current or previous psychiatric disorder or environmental factors such as specific lifestyles that could have led to adaptive changes in corticosteroid receptor function in our subjects, we conclude that our findings are best understood as indicating a genetically transmitted risk factor, possibly rendering these individuals susceptible to affective disorders.