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

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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