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

通过针对可乐定的 _<alpha2> 肾上腺素能受体的神经内分泌反应来研究抑郁症

• 批准号: 62570490
• 负责人: KISHIMOTO Akira
• 金额: $ 0.32万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570490/
• 关键词: adrenergic alpha_2 receptor; clonidine; cortisol; human growth hormone; MHPG; depression; アドレナリン性α_2-受容体; コルチゾール; 成長ホルモンプロラクチン; アドレナリン性α_<>受容体; プロラクチン; セロトニン

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

最近，中枢单胺能受体敏感性异常被认为是抑郁症的一种发病机制。为了阐明α2受体在抑郁症中的反应性，本研究比较了抑郁症患者、神经性抑郁症(心境恶劣障碍)患者和正常对照组的神经内分泌反应(人生长激素：HGH、皮质醇：COR、3-甲氧基-4-羟基苯乙醇：MHPG)对急性口服可乐定的影响。可乐定可刺激HGH的分泌，显著降低所有受试者的血浆COR和MHPG水平。抑郁症患者HGH、COR和MHPG对可乐定的反应明显低于对照组。神经症性抑郁症患者对可乐定的COR反应与对照组无差异，但可乐定后HGH分泌较对照组减少。血浆COR的差异。Level…在可乐定负荷后，可乐定负荷变得更加突出之前，对照组与抑郁组之间的差别更大。两组在可乐定负荷后的最大HGO水平与COR反应(COR从基线水平下降)显著相关。脱毛组基础MHPG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，基础MHPG水平与HGH或COR水平之间没有明显的相关性。推测抑郁症患者α2受体敏感性降低，尤其是突触后受体敏感性降低，导致下丘脑-垂体-肾上腺(HPA)系统活动增加，HGH分泌减少。突触后α2受体在抑郁症中的低敏感性被认为是由于突触前去甲肾上腺素能活动增加与HPA升高有关。在大多数对照组中，可乐定的最低血药浓度分布在6.0mug/dl以下。另一方面，在大约一半的抑郁症患者中，这些都高于价值。当COR标准值为6.0mug/dl时，可乐定负荷试验诊断抑郁症的敏感度为54.5%，特异度为95.5%，诊断准确度为96.0%。这些测定值与抑郁症地塞米松抑制试验(DST)的测定值相当。因此，可乐定负荷可能是诊断抑郁症的一种有用的生物学工具。较少

项目成果

Kishimoto, A.,: "Abnormality of alpha_2 adrenergic receptor sensitivity in depression" "Japanese Journal of Neuropsychopharmacology".

Kishimoto, A.，：“抑郁症中 α_2 肾上腺素受体敏感性异常”，《日本神经精神药理学杂志》。

Kishimoto,A.,et al.: "Clonidine-induced secretion of human growth hormone is correlated to decrease of cortisol" Japanese Journal of Psychiatry and Neurology.

Kishimoto,A.,et al.：“可乐定诱导的人类生长激素分泌与皮质醇的减少相关”《日本精神病学和神经病学杂志》。

中村準一: "アドレナリン性α_2受容体アゴニスト負荷によるうつ病の神経内分秘反応とα_2受容体機能について" 九州神経精神医学. 34. 239-251 (1988)

Junichi Nakamura：“关于肾上腺素能 α_2 受体激动剂负载引起的抑郁症中的神经元内分泌反应和 α_2 受体功能”九州神经精神病学 34. 239-251 (1988)。

Kishimoto, A.,: "Clonidine-induced secretion of human growth hormone is correlated to decrease of cortisol" "The Japanese Journal of Psychiatry and Neurology".

Kishimoto, A.：“可乐定诱导的人类生长激素分泌与皮质醇的减少相关”“日本精神病学和神经病学杂志”。

Nakamura, J.: "Neuroendocrinological response to an alpha 2 adrenergic receptor against in depression" The Kyushu Neuro-Psychiatry. 34. 239-251 (1988)

Nakamura, J.：“抑郁症中α2肾上腺素受体的神经内分泌反应”九州神经精神病学。