Stress hormone dysregulation at rest and after serotonergic stimulation among alcohol-dependent men with extended abstinence and controls
Stress hormone dysregulation at rest and after serotonergic stimulation among alcohol-dependent men with extended abstinence and controls
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DOI：
10.1111/j.1530-0277.2001.tb02269.x
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发表时间：
2001-05-01
影响因子：
3.2
通讯作者：
Hauger, R
中科院分区：
文献类型：
--
作者：
Anthenelli, RM;Maxwell, RA;Hauger, R
背景：酒精依赖与边缘-下丘脑-垂体-肾上腺（LHPA）轴和5-羟色胺（5-羟色胺[5-HT]）功能的长期改变有关。与酗酒相关的其他情况（吸烟和反社会人格障碍[ASPD]）也与这些相关系统的紊乱有关。我们评估了长期戒酒（平均戒酒时间为4.3个月）的酒精依赖男性和对照组的应激激素对5-羟色胺刺激的反应，以确定酒精中毒、吸烟和ASPD对基线和诱发血浆皮质醇和促肾上腺皮质激素（ACTH）浓度的相对贡献。方法：在一项随机、双盲、安慰剂对照的交叉试验中，109名酒精依赖（62%）、习惯性吸烟（70%）和反社会人格障碍（43%）的戒酒男性接受了D， l-芬氟拉明（100mg / po）治疗。恢复酒精依赖个体组包括戒酒的原发性酒精依赖男性和患有反社会人格障碍的酒精依赖男性，而非酒精依赖男性组包括健康对照组和患有反社会人格障碍的非酒精依赖男性。血浆皮质醇和ACTH水平分别在AM基线和给药后半小时获得。在基线和每30分钟获得药物反应和生理指标的主观评分。结果：在两个挑战日，戒酒的酒精依赖男性的AM基线血浆皮质醇浓度显著低于非酒精依赖男性（约20%）；然而，在静息AM血浆ACTH水平方面，各组之间没有观察到差异。在调整这些基线差异之后。恢复中的酒精依赖男性（曲线下面积= 35.6 +/- 37.4[杯/分升]x分钟）对芬氟拉明的皮质醇反应是非酒精依赖男性（曲线下面积= 17.5 +/- 32.5[杯/分升]x分钟）的两倍（F = 5.1; df = 1105; p < 0.03）。升高的皮质醇反应主要发生在反应曲线的降肢，与非酒精依赖男性相比，酒精依赖男性在210分钟（p < 0.07）和240分钟（p < 0.09）时间点对芬氟拉明的ACTH反应也表现出更大的统计学趋势。吸烟和反社会人格障碍对激素反应没有影响，两组的主观评分和生理指标也无法区分。结论：长期戒酒的酒精依赖男性与年龄和种族匹配的非酒精依赖男性在静息AM和芬氟拉明诱导的血浆皮质醇水平上存在差异。糖皮质激素体内平衡机制的这种功能障碍与酗酒有关，而与吸烟或反社会人格障碍无关。我们还观察到，在酒精依赖男性中，血浆ACTH水平沿反应曲线的下降趋势升高，但统计学趋势不显著。酒精依赖者似乎遗传或获得了对5- ht调节的LHPA轴功能的损害，其确切机制和位置仍有待确定。
Background: Alcohol dependence has been associated with long-lasting alterations in limbic-hypohalamic-pituitary-adrenal (LHPA) axis and serotonin (5-hydroxytryptamine [5-HT]) function. Other conditions that are associated with alcoholism (cigarette smoking and antisocial personality disorder [ASPD]) have been linked with disturbances in these interrelated systems. We evaluated the stress hormone response to 5-HTergic stimulation in alcohol-dependent men with extended abstinence (average abstinence duration, 4.3 months) and controls to determine the relative contributions of alcoholism, cigarette smoking, and ASPD on baseline and provoked plasma cortisol and adrenocorticotropin hormone (ACTH) concentrations.Methods: One hundred nine alcohol-abstinent men with alcohol dependence (62%), habitual smoking (70%), and ASPD (43%) received D,L-fenfluramine (100 mg po) in a randomized, double-blind, placebo-controlled, crossover trial. The group of recovering alcohol-dependent individuals included abstinent primary alcohol-dependent men and alcohol-dependent men with ASPD, whereas the group of non-alcohol-dependent men comprised healthy controls and non-alcohol-dependent men with ASPD. plasma cortisol and ACTH levels were obtained at AM baseline and at half-hour intervals after drug administration. Subjective ratings of drug response and physiological measures were also obtained at baseline and every 30 min.Results: Abstinent alcohol-dependent men had significantly lower (approximately 20%) AM baseline plasma cortisol concentrations than non-alcohol-dependent men on both challenge days; however, no differences between the groups were observed with regard to resting AM plasma ACTH levels. After adjusting for these baseline differences. recovering alcohol-dependent men (area under curve = 35.6 +/- 37.4 [mug/dl] x min) had a twofold greater cortisol response to fenfluramine than non-alcohol-dependent men (area under curve = 17.5 +/- 32.5 [mug/dl] x min) (F = 5.1; df = 1,105; p < 0.03). The elevated cortisol response, which occurred primarily along the descending limb of the response carve, was paralleled by a nonsignificant statistical trend for alcohol-dependent men to also exhibit a greater ACTH response to fenfluramine at the 210-min (p < 0.07) and 240-min (p < 0.09) time points as compared with non-alcohol dependent men. Cigarette smoking and ASPD did not affect hormonal responses, nor could the groups' subjective ratings and physiological measures be distinguished.Conclusions: Alcohol-dependent men with extended abstinence differed from age- and race-matched non-alcohol-dependent men in resting AM and fenfluramine-induced plasma cortisol levels. This dysfunction in glucocorticoid homeostatic mechanisms was associated with alcoholism and not with smoking or ASPD. We also observed a nonsignificant statistical trend for plasma ACTH levels to be elevated among alcohol-dependent men along the descending limb of the response curve. Alcohol-dependent men seemed to have inherited or acquired damage to 5-HT-regulated LHPA axis function, the precise mechanisms and sites of which remain to be determined.