Schuckit M A, Tsuang J W, Anthenelli R M, Tipp J E, Nurnberger J I
Department of Psychiatry (116A), Veterans Affairs Medical Center, San Diego, USA.
J Stud Alcohol. 1996 Jul;57(4):368-77. doi: 10.15288/jsa.1996.57.368.
Alcoholism is a complex disorder that demonstrates genetic heterogeneity. Genetic linkage studies of alcohol dependence also suffer from the probability that many individuals who inherit an enhanced risk never develop the clinical syndrome. Thus, studies of genetic influences in alcohol abuse or dependence would benefit from the identification of characteristics of an individual that are associated with the probability of developing the disorder. A reduced responsivity to alcohol has been reported to characterize almost 40% of sons of alcoholics and to predict future alcohol abuse or dependence a decade later. This study explores the existence of this characteristic in a more heterogeneous sample that is part of a genetic pedigree study of families of alcoholics.
Eighteen to 30 year old subjects who were sons of alcohol dependent fathers and who were drinkers but not alcohol dependent were selected from pedigrees of alcoholics at all six sites of the Collaborative Study on the Genetics of Alcoholism (COGA) study. Family history negative controls matched on demography and substance use histories were selected for each subject. Data were obtained on 20 pairs of high-risk and low-risk men (40 subjects) following a challenge with 0.72 g/kg (0.9 ml/kg) of ethanol. Evaluations included measures of subjective feelings of intoxication and body sway, and changes in cortisol, ACTH and prolactin.
The data corroborate a lower level of intensity of response to alcohol in the sons of alcoholics especially as measured by changes in cortisol, with similar but less robust changes in subjective feelings and other measures.
The results expand upon earlier studies by using a more heterogeneous population of men at high alcoholism risk. The data highlight the possible usefulness of the reduced response to alcohol as an adjunct to future linkage analyses.
酒精中毒是一种表现出遗传异质性的复杂疾病。酒精依赖的遗传连锁研究也存在这样的可能性，即许多遗传了增加风险的个体从未发展出临床综合征。因此，对酒精滥用或依赖的遗传影响进行研究，若能识别出与该疾病发生概率相关的个体特征将大有裨益。据报道，近40%的酗酒者之子对酒精的反应性降低，且能预测十年后未来的酒精滥用或依赖情况。本研究在一个更具异质性的样本中探究这一特征的存在情况，该样本是酗酒者家庭遗传谱系研究的一部分。
从酒精中毒遗传学协作研究（COGA）的所有六个研究地点的酗酒者谱系中，选取年龄在18至30岁之间、父亲为酒精依赖者、饮酒但非酒精依赖的男性作为研究对象。为每个研究对象选取在人口统计学和物质使用史方面匹配的家族史阴性对照。在给予0.72 g/kg（0.9 ml/kg）乙醇激发后，获取了20对高风险和低风险男性（40名研究对象）的数据。评估包括醉酒主观感受、身体摇摆的测量，以及皮质醇、促肾上腺皮质激素和催乳素的变化。
数据证实了酗酒者之子对酒精的反应强度较低，尤其是通过皮质醇变化来衡量，主观感受和其他测量方面也有类似但不太明显的变化。
本研究结果通过使用一个更具异质性的高酒精中毒风险男性群体，扩展了早期研究。数据突出了酒精反应性降低作为未来连锁分析辅助手段的潜在有用性。
