抑郁患者的早期生活压力：HPA 轴对 GR 和 MR 激动剂的反应。
Early Life Stress in Depressive Patients: HPA Axis Response to GR and MR Agonist.
机构信息
Stress and Affective Disorders - SAD Program, Mental Health Graduate Program, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil.
Stress and Affective Disorders - SAD Program, Mental Health Graduate Program, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil ; Institute of Psychiatry, King's College London , London , UK.
出版信息
Front Psychiatry. 2014 Jan 24;5:2. doi: 10.3389/fpsyt.2014.00002. eCollection 2014.
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.
背景
有证据表明，早期生活压力（ELS）会导致成年后应对压力的下丘脑-垂体-肾上腺（HPA）轴持续变化，从而导致抑郁。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。本研究旨在评估 ELS 对 HPA 轴对 GR 和 MR 激动剂反应的影响在抑郁患者中。
方法
我们纳入了 30 名受试者，其中 20 名为目前患有重度抑郁症（HAM-D21≥17）的患者。根据童年创伤问卷（CTQ）评估 ELS 病史，将患者分为两组。在晚上 10 点使用安慰剂、氟氢可的松（MR 激动剂）或地塞米松（GR 激动剂）后，评估唾液和血浆中的皮质醇水平。
结果
与对照组相比，抑郁患者在服用安慰剂后醒来时唾液皮质醇明显较低。此外，与对照组相比，抑郁患者在服用 MR 激动剂后皮质醇觉醒反应（CAR）较低。在 CTQ 评分、HAM-D21、体重指数和安慰剂、GR 激动剂、MR 激动剂后的 CAR 方面，我们发现线性回归模型中，有 ELS 的抑郁患者（p=0.028）显示 ELS 组与 MR 激动剂组之间的差异（R=0.51;p<0.05），但 GR 激动剂组无差异；在无 ELS 的抑郁患者中，安慰剂与 MR 激动剂之间存在差异（R=0.69;p<0.05）；但是现在安慰剂与 GR 激动剂之间也存在差异（R=0.53;p<0.05）。
结论
我们的研究结果表明，与对照组相比，MR 活性在抑郁患者中受损。此外，尽管存在先前描述的局限性，在有 ELS 的抑郁患者中，MR 激动剂存在抑制作用，表明 ELS 患者对 MR 激动剂敏感。与无 ELS 的抑郁患者不同，我们发现 MR 和 GR 激动剂后均有抑制作用。这些数据表明，在 ELS 中，MR 和 GR 之间存在失衡，MR 功能障碍。
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