Early Life Stress in Depressive Patients: HPA Axis Response to GR and MR Agonist.
Early Life Stress in Depressive Patients: HPA Axis Response to GR and MR Agonist.
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DOI：
10.3389/fpsyt.2014.00002
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发表时间：
2014
影响因子：
4.7
通讯作者：
Juruena MF
中科院分区：
文献类型：
--
作者：
Baes Cv;Martins CM;Tofoli SM;Juruena MF
背景资料：有证据表明，早期生活应激（ELS）可以诱导下丘脑-垂体-肾上腺（HPA）轴的持续变化，以应对成年生活中导致抑郁症的应激。这些似乎与HPA激素通过与糖皮质激素（GR）和盐皮质激素受体（MR）结合而受损有关。本研究的目的是评估ELS对抑郁症患者HPA轴对GR和MR激动剂刺激反应的影响。方法：选取30例受试者，20例抑郁症患者（HAM-D21 ≥ 17）。根据儿童期创伤问卷（CTQ）评估的ELS病史，将患者分为两组。在使用后（在晚上10：00）评价唾液和血浆中的皮质醇测量。安慰剂、氟氢可的松（MR激动剂）或地塞米松（GR激动剂）。结果：与对照组相比，抑郁症患者在服用安慰剂后清醒时唾液皮质醇显著降低。此外，皮质醇觉醒反应（CAR）后MR激动剂被发现在抑郁症患者低于对照组。与安慰剂、GR激动剂、MR激动剂治疗后的CTQ评分、HAM-D21、体重指数和CAR进行线性回归分析，发现ELS抑郁患者（p = 0.028）显示安慰剂与MR激动剂之间的差异（R = 0.51; p < 0.05），但GR激动剂治疗后无差异;在抑郁症患者中，无ELS，数据显示安慰剂与MR激动剂之间存在差异（R = 0.69; p < 0.05）;但现在也是安慰剂对比GR激动剂（R = 0.53; p < 0.05）。结论：我们的研究结果表明，与对照组相比，抑郁症患者的MR活动受损。此外，尽管存在上述局限性，但在患有ELS的抑郁患者中，MR激动剂存在抑制作用，表明患有ELS的患者对MR激动剂敏感。与没有ELS的抑郁症患者相比，我们发现MR和GR激动剂后抑制。这些数据表明，在ELS中MR和GR之间存在不平衡，MR功能障碍。
Background: Evidence indicates that early life stress (ELS) can induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress in the adult life that leads to depression. These appear to be related to the impairment of HPA hormones through binding to glucocorticoid (GR) and mineralocorticoid receptors (MR). The aim of this study was to evaluate the impact of ELS in HPA axis response to challenges with GR and MR agonists in depressed patients. Methods: We included 30 subjects, 20 patients with current major depression (HAM-D21 ≥ 17). Patients were recruited into two groups according to ELS history assessed by the Childhood Trauma Questionnaire (CTQ). The cortisol measures in the saliva and plasma were evaluated after using (at 10:00 p.m.) placebo, fludrocortisone (MR agonist), or dexamethasone (GR agonist). Results: Depressed patients showed a significantly lower salivary cortisol upon waking after placebo compared with controls. Moreover, cortisol awakening responses (CAR) after MR agonist were found to be lower in depressed patients than in controls. With CTQ scores, HAM-D21, body mass index and CAR after placebo, GR agonist, MR agonist we found in a Linear Regression model that depressive patients with ELS (p = 0.028) show differences between placebo vs. MR agonist (R = 0.51; p < 0.05) but not after GR agonist; in depressive patients, without ELS the data show differences between placebo vs. MR agonist (R = 0.69; p < 0.05); but now as well placebo vs. GR agonist (R = 0.53; p < 0.05). Conclusion: Our findings indicate that MR activity is impaired in depressed patients compared with controls. Furthermore, in spite of the previous limitations described, in depressed patients with ELS, there was suppression by MR agonist, indicating that patients with ELS are sensitive to MR agonists. In contrast with depressed patients without ELS, we find suppression after both MR and GR agonist. These data suggested that in ELS an imbalance exists between MR and GR with MR dysfunction.
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影响因子：
10.5
作者：
CARROLL, BJ
通讯作者：
CARROLL, BJ
影响因子：
3.7
作者：
Adam, Emma K.;Doane, Leah D.;Zinbarg, Richard E.;Mineka, Susan;Craske, Michelle G.;Griffith, James W.
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Veldhuis, J. D.
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作者：
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通讯作者：
Parker, Gordon