Connan Frances, Lightman Stafford L, Landau Sabine, Wheeler Michael, Treasure Janet, Campbell Iain C
Institute of Psychiatry, KCL, London, SE5 8AF, UK.
J Psychiatr Res. 2007 Jan-Feb;41(1-2):131-43. doi: 10.1016/j.jpsychires.2005.12.005. Epub 2006 Feb 7.
We hypothesised that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in anorexia nervosa (AN) is associated with (a) elevated arginine vasopressin (AVP) activity and (b) enhanced pituitary sensitivity to AVP, as it is in depressive illness. 16 Healthy women and 18 women with active AN participated in a combined dexamethasone (DXM)/corticotrophin releasing hormone (CRH) challenge test and an AVP challenge test. This combination of tests is designed to assess the functional contribution of AVP to HPA axis activity. 10 of the active AN group repeated participation after weight gain. The cortisol response to AVP was reduced by 138% in the active AN group, suggesting an impairment of pituitary sensitivity to AVP, which began to normalise with weight gain. The cortisol and adreno-corticotrophin (ACTH) responses to the DXM/CRH test were not significantly enhanced in the active AN group, suggesting that there was no elevated endogenous AVP activity augmenting the response to CRH in AN. Weight gain was associated with blunting of the endocrine response to the DXM/CRH test, which may have been related to rising oestrogen levels. Thus, contrary to the hypotheses, we did not find (a) evidence of upregulated AVP activity or (b) enhanced pituitary sensitivity to AVP in AN. These findings suggest that the mechanism of HPA axis hyperactivity differs in depression and AN, with greater involvement of AVP in depressive disorder and perhaps more reliance on CRH to drive the axis in AN. The powerful anorexigenic effect of CRH could contribute to the severity of weight loss associated with AN.
我们假设,与抑郁症一样,神经性厌食症(AN)患者下丘脑-垂体-肾上腺(HPA)轴功能亢进与以下因素有关:(a)精氨酸加压素(AVP)活性升高;(b)垂体对AVP的敏感性增强。16名健康女性和18名患有活动性AN的女性参与了一项联合地塞米松(DXM)/促肾上腺皮质激素释放激素(CRH)激发试验以及一项AVP激发试验。这种试验组合旨在评估AVP对HPA轴活性的功能作用。10名患有活动性AN的受试者在体重增加后再次参与试验。在活动性AN组中,皮质醇对AVP的反应降低了138%,这表明垂体对AVP的敏感性受损,而随着体重增加这种敏感性开始恢复正常。在活动性AN组中,对DXM/CRH试验的皮质醇和促肾上腺皮质激素(ACTH)反应并未显著增强,这表明在AN患者中没有内源性AVP活性升高来增强对CRH的反应。体重增加与对DXM/CRH试验的内分泌反应减弱有关,这可能与雌激素水平升高有关。因此,与假设相反,我们没有发现:(a)AN患者存在AVP活性上调的证据;(b)垂体对AVP的敏感性增强。这些发现表明,HPA轴功能亢进的机制在抑郁症和AN中有所不同,在抑郁症中AVP的参与程度更高,而在AN中可能更多地依赖CRH来驱动该轴。CRH强大的厌食作用可能导致了与AN相关的体重减轻的严重程度。