Zimmermann Ulrich, Spring Konstanze, Kunz-Ebrecht Sabine Ruth, Uhr Manfred, Wittchen Hans-Ulrich, Holsboer Florian
Max-Planck-Institute of Psychiatry, Kraepelinstrasse, Munich, Germany.
Neuropsychopharmacology. 2004 Jun;29(6):1156-65. doi: 10.1038/sj.npp.1300395.
Familial risk and environmental stress promote the development of alcohol dependence. This study tested two hypotheses: that a family history for alcoholism is associated with (i) a greater stress response and (ii) more effective stress response dampening by alcohol. We studied 29 high-risk subjects with a paternal history of alcoholism (PHA) and 23 family history negative (FHN) controls all aged 18-26 years, who were recruited using a representative sample of the local area population. Psychosocial stress was induced by having subjects deliver a speech and perform mental arithmetics in front of an audience on two separate days, after drinking either placebo or alcohol (0.6 g/kg) in a randomized double-blind crossover design. Plasma cortisol and adrenocorticotropin (ACTH) were measured up to 90 min after the test. The stress task induced a phasic increase of both hormones in PHA and FHN subjects during all experimental conditions except in tests where FHN subjects received alcohol during the second day. ACTH secretion was higher in PHA subjects during placebo experiments, but equal to controls after alcohol administration. The alcohol-induced attenuation of ACTH response was statistically significant in PHA, but not FHN, subjects. Cortisol response was higher in PHA than FHN probands if placebo was administered during the first test, but equal if subjects received alcohol first. The increased stress response and its stronger dampening by alcohol in sons of alcoholic fathers suggest a mechanism by which predisposition to develop alcohol use disorders might be expressed, implying that a transient favorable alcohol effect might occur in PHA, but not FHN, subjects.
家族风险和环境压力会促使酒精依赖的发展。本研究检验了两个假设：酗酒家族史与（i）更强的应激反应以及（ii）酒精对应激反应的更有效抑制有关。我们研究了29名有父亲酗酒家族史（PHA）的高危受试者和23名无家族史（FHN）的对照者，所有受试者年龄在18 - 26岁之间，他们是从当地人口的代表性样本中招募的。通过让受试者在两天内分别在观众面前进行演讲和做心算来诱发心理社会压力，采用随机双盲交叉设计，受试者在饮用安慰剂或酒精（0.6 g/kg）后进行测试。在测试后长达90分钟内测量血浆皮质醇和促肾上腺皮质激素（ACTH）。在所有实验条件下，应激任务都会使PHA和FHN受试者体内这两种激素呈阶段性升高，但在第二天FHN受试者饮用酒精的测试中除外。在安慰剂实验期间，PHA受试者的ACTH分泌较高，但饮酒后与对照组相当。酒精诱导的ACTH反应减弱在PHA受试者中具有统计学意义，但在FHN受试者中则不然。如果在第一次测试中给予安慰剂，PHA先证者的皮质醇反应高于FHN先证者，但如果受试者先饮酒，则两者相当。酗酒父亲的儿子中应激反应增强以及酒精对其更强的抑制作用表明了一种可能表达酒精使用障碍易感性的机制，这意味着在PHA受试者而非FHN受试者中可能会出现短暂的酒精有益效应。
