HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients
HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients
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DOI：
10.1016/j.psyneuen.2008.08.018
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发表时间：
2009-01-01
影响因子：
3.7
通讯作者：
Holsboer, F.
中科院分区：
文献类型：
--
作者：
Binder, E. B.;Kuenzel, H. E.;Holsboer, F.
一系列数据表明，下丘脑-垂体-肾上腺（HPA）轴的过度活跃在抑郁症的发病机制中，其正常化是抗抑郁药物临床反应的必要前提。此外，hpa轴的调节已被证明依赖于性激素。因此，我们研究了抑郁症中hpa轴调节的性别差异及其在临床症状缓解期间的正常化。我们采用地塞米松抑制/CRH刺激（Dex-CRH）联合试验来评估194例入院和出院时来自慕尼黑抗抑郁反应特征（MARS）研究的单极抑郁症住院患者的hpa轴失调程度。采用汉密尔顿抑郁量表（HAM-D）监测抗抑郁药物治疗的临床反应。对于两种性别，我们观察到在治疗5周后和出院时，缓解者的hpa轴失调正常化，而非缓解者的hpa轴失调正常化。然而，随着抑郁症状的缓解，hpa轴正常化的模式显示出性别特异性差异。在大多数患者中，住院治疗5周后的缓解与入院时Dex-CRH测试中明显较高的皮质醇反应相关。在女性患者中，5周缓解者和未缓解者入院时的皮质醇反应相当。入院时的皮质醇反应与此时间点的性腺类固醇水平无关，绝经前妇女与绝经后妇女的结果相似。性别相关的生物学特征，可能独立于循环性腺类固醇，因此似乎影响抑郁症中hpa轴的调节。在大多数患者中，除了先前报道的Dex-CRH测试重复测量外，入院时hpa轴失调的单一测量可以作为抗抑郁治疗反应的预测因子。(C) 2008 Elsevier Ltd版权所有。
A concatenation of data implicates a hyperactivity of the hypothalamus pituitary adrenal (HPA)-axis in the pathogenesis of depression and its normalization as a necessary predecessor of clinical response to antidepressant drugs. In addition, regulation of the HPA-axis has been shown to be dependent on sex hormones. We therefore investigated gender differences in HPA-axis regulation in depression and its normalization during remission of clinical symptoms. We used the combined dexamethasone suppression/CRH stimulation (Dex-CRH) test to evaluate the degree of HPA-axis dysregulation in 194 in-patients with unipolar depression from the Munich Antidepressant Response Signature (MARS) study at both admission and discharge. The Hamilton Depression (HAM-D) Rating Scale was used to monitor clinical response to antidepressant treatment. For both genders, we observed a normalization of HPA-axis dysregulation in remitters but not in non-remitters, both after 5 weeks of treatment and at discharge. The pattern of HPA-axis normalization with remission of depressive symptoms, however, showed gender-specific differences. In mate patients, remission after 5 weeks of in-patient treatment was associated with a significantly higher cortisol response in the Dex-CRH test at admission. In female patients, 5-week remitters and non-remitters had a comparable cortisol response at admission. Cortisol response at admission was not correlated with gonadal steroid levels at this time point and the results were similar for pre-menopausal women vs. post-menopausal women. Gender-associated biological characteristics, likely independent of circulating gonadal steroids, thus seem to influence HPA-axis regulation in depression. In mate patients, a single measure of HPA-axis dysregulation at admission may serve as a predictor of response to antidepressant treatment in addition to the previously reported repeated measure of the Dex-CRH test. (C) 2008 Elsevier Ltd. All rights reserved.