A study of depression through neuroendocrinological responses to an _<alpha2> adrenergic receptor against clonidine

最近，中枢单胺能受体敏感性异常被认为是抑郁症的发病机制之一。为了阐明α 2肾上腺素能受体在抑郁症中的反应性，本项目比较了抑郁症患者、神经性抑郁症（心境不良）患者和正常健康对照者急性口服α 2受体抗可乐定的神经内分泌反应（人生长激素：HGH，皮质醇：COR，3-甲氧基-4-羟基苯基-乙二醇：MHPG）。可乐定刺激HGH分泌，显著降低血浆COR和MHPG水平。抑郁症患者HGH、COR和MHPG对可乐定的反应较对照组明显降低。神经性抑郁症患者对可乐定的COR反应与对照组无差异，但与对照组相比，可乐定后HGH分泌减少。对照组和抑郁组血浆co .水平在可乐定加载前比较明显，在可乐定加载后比较明显。可乐定负荷后的最大HGO水平与两组的COR反应（COR从基线水平下降）显著相关。抑郁组负荷后MHPG基线水平与最大HGH水平呈显著负相关，与COR水平呈显著正相关。然而，在对照组中，基线MHPG水平与HGH或COR水平没有显著相关性。由此推测，抑郁症患者α - 2受体的敏感性，尤其是突触后受体的敏感性降低，导致下丘脑-垂体-肾上腺（HPA）系统亢进和HGH分泌减少。我们认为抑郁症突触后α 2受体的低敏感性是由突触前去甲肾上腺素能活性增加引起的，与HPA亢进有关。接下来，检查了可乐定负荷试验的诊断效用。在大多数对照受试者中，可乐定后的最低COR水平分布在6.0mug/dl以下。另一方面，在大约一半的抑郁症患者中，这些都高于这个值。当COR的标准值为6.0马克/分升时，该版本的可乐定负荷试验识别抑郁症患者的敏感性为54.5%，特异性为95.5%，诊断置信度为96.0%。该试验获得的这些值与地塞米松抑制试验（DST）在抑郁症中的结果相当。因此，建议可乐定负荷可能是一种有用的生物学工具，作为抑郁症的诊断测试。少

Recently, abnormality in central monoaminergic receptor sensitivity is postulated as a pathogenesis of depression. In order to clarify the responsiveness of alpha 2 adrenergic receptor in depression, neuroendocrinological responses (human growth hormone: HGH, cortisol: COR,3-methoxy-4-hydroxyphenyl- glycol: MHPG) to acute oral administration of alpha 2 receptor against clonidine were compared between patients with depression, patients with neurotic depression (dysthymic disorder) and normal healthy controls in this project. Clonidine stimulated HGH secretion and significantly reduced plasma COR and MHPG levels in all subject groups. The responses of HGH, COR and MHPG to clonidine in patients with depression were significantly reduced compared with control subjects. In patients with neurotic depression, COR response to clonidine did not differ from that in control subjects, but HGH secretion after clonidine was reduced compared with control subjects. The difference in Plasma COR. level … More seen between the control group and the depressed group before the clonidine loading became more prominent after the clonidine loading. The maximum HGO level after the clonidine loading significantly correlated to COR response (COR fall from baseline level) in the both groups. In depiessed group, baseline MHPG level showed significantly negative correlation with maxioul HGH level and also positive correlation with COR level after the loading. However, no significant correlation between baseline MHPG level and HGH or COR level was observed in controls. From these results, it was speculated that alpha 2 receptor sensitivity, especially postsynaptic one is reduced in depression and the hyposensitivity resulted in hyperactivity of hypothalanic-pituitary-adrenal (HPA) system and in hyposecretion of HGH. It was considered that the hyposensitivity of postsynaptic alpha 2 receptor in depression was caused by increased presynaptic noradrenergic activity associated with HPA hyper.Next, the diagnostic utility of the clonidine loading test was examined. In most of the control subjects, the minimum COR levels after clonidine distributed under 6.0mug/dl. On the other hard, in about a half of depressed patients those were above the value. When the criterion value of COR was 6.0 mug/dl, this version of the clonidine loading test identified depressed patients with a sensitivity of 54.5%, a specificity of 95.5% and a diagnostic confidence of 96.0%. These values obtained by this test are comparable to those by the dexamethasone suppression test (DST) in depression. Therefore, it is suggested that clonidine loading may be useful biological tool as a test for the diagnosis of depression. Less