Hubers A A M, van der Mast R C, Pereira A M, Roos R A C, Veen L J, Cobbaert C M, van Duijn E, Giltay E J
Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
J Neuroendocrinol. 2015 Mar;27(3):234-44. doi: 10.1111/jne.12255.
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in Huntington's disease (HD). In non-HD populations, alterations in HPA axis activity have been associated with depression and suicidality. The present study aims to compare HPA axis activity between HD mutation carriers and controls, and examine its association with depressive symptoms and suicidality. To this end, salivary cortisol concentrations at seven time points, as well as depressive symptoms and suicidality, were assessed in 49 pre-motor, 102 motor symptomatic mutation carriers and 55 controls, at baseline and follow-up combined. Differences in parameters of HPA axis activity between these three groups, and their associations with depressive symptoms and suicidality in HD mutation carriers, were analysed using multilevel regression analyses. There were no differences in parameters of HPA axis activity between mutation carriers and controls, whereas pre-motor symptomatic mutation carriers had a significantly higher area under the curve to the increase (AUCi ) compared to motor symptomatic mutation carriers. In the entire HD cohort, HPA axis activity was not associated with depressive symptoms or suicidality. After stratifying mutation carriers into pre-motor, early and advanced disease stages, β values differed between these groups. Remarkably, a higher AUCi was significantly associated with depressive symptoms in pre-motor and early disease stage mutation carriers, with a reverse nonsignificant association in advanced disease stage mutation carriers. The lower AUCi in motor symptomatic mutation carriers and the varying associations with depressive symptoms and suicidality in pre-motor, early and advanced disease stages could possibly be explained by exhaustion of the HPA axis after prolonged stress-induced HPA axis hyperactivity and deserves further longitudinal study.
据报道，亨廷顿舞蹈病（HD）患者存在下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进。在非HD人群中，HPA轴活性改变与抑郁和自杀倾向有关。本研究旨在比较HD突变携带者与对照组之间的HPA轴活性，并研究其与抑郁症状和自杀倾向的关联。为此，对49名运动前期、102名有运动症状的突变携带者和55名对照者在基线和随访时的七个时间点的唾液皮质醇浓度以及抑郁症状和自杀倾向进行了评估。使用多水平回归分析，分析了这三组之间HPA轴活性参数的差异，以及它们与HD突变携带者抑郁症状和自杀倾向的关联。突变携带者与对照组之间的HPA轴活性参数没有差异，而运动前期有症状的突变携带者与有运动症状的突变携带者相比，曲线下面积增加值（AUCi）显著更高。在整个HD队列中，HPA轴活性与抑郁症状或自杀倾向无关。将突变携带者分为运动前期、疾病早期和晚期后，这些组之间的β值有所不同。值得注意的是，较高的AUCi与运动前期和疾病早期突变携带者的抑郁症状显著相关，而与疾病晚期突变携带者呈反向非显著关联。有运动症状的突变携带者的AUCi较低，以及运动前期、疾病早期和晚期与抑郁症状和自杀倾向的不同关联，可能是由于长期应激诱导的HPA轴功能亢进后HPA轴耗竭所致，值得进一步进行纵向研究。
