Glucocorticoid receptor antagonism and cognition in alcoholics

酒精依赖是一种慢性复发性疾病，据卫生部最近估计，其发病率占成年人口的7%。目前，在设法戒酒的酗酒者中，高达90%的人会在一年内重新酗酒。酒精依赖是一个主要的健康问题，饮酒会导致许多其他的医疗疾病和广泛的社会问题。50%至80%的酗酒者因饮酒而导致记忆问题，许多人还存在其他健康问题，特别是抑郁症。前者的症状很难治疗，很大程度上是因为导致记忆问题的大脑变化尚不清楚，也因为过度饮酒的模式不同。如果了解了记忆问题所涉及的机制，这将使有效的治疗方法得以开发，从而提高生活质量并降低医疗成本。最近的实验室和临床研究表明，当一个人停止过度饮酒时，大脑的变化是导致记忆缺陷的原因。众所周知，过量的应激激素糖皮质激素会损害大脑中的神经，导致记忆力丧失，在酒精解毒过程中，这些激素会释放出高浓度的激素。研究还表明，一种名为米非司酮的药物可以阻止重要的应激激素皮质醇对一种名为II型糖皮质激素受体的特定大脑蛋白质的作用，这种药物对患有记忆问题的人和临床上患有抑郁症的人都有有益的影响，但这一点尚未在酗酒者中进行研究。然而，实验室研究表明，阻止皮质醇对这种受体蛋白的作用可以减少长期饮酒造成的神经损伤。该项目将测量药物米非司酮在一组进入治疗单元接受酒精戒毒的酗酒者中的效果。将对认知能力测试中的表现和抑郁症状进行衡量，因为后者可能导致记忆力丧失。如果这个项目的结果是肯定的，这将表明受体蛋白参与了记忆缺陷和/或抑郁症状的发生。这些知识将有助于开发新的治疗方法，为大量酗酒者遭受的这些问题提供有效的治疗方法。

Alcohol dependence is a chronic relapsing disease, the incidence of which was recently estimated by the Department of Health to be 7% of the adult population. Currently, up to 90% of alcoholics who manage to stop drinking relapse back to the alcohol within a year. Alcohol dependence is a major health problem, and the alcohol consumption causes many other medical disorders and extensive social problems. Between 50 and 80% of alcoholics suffer from memory problems caused by the alcohol consumption and many also have other medical problems, particularly depression. The former symptoms are very difficult to treat, largely because the changes in the brain that cause the memory problems are not yet understood, and also because there are different patterns of excess alcohol drinking. If the mechanisms involved in the memory problems are understood, this will enable effective treatments to be developed that will improve quality of life and reduce health costs. Recent laboratory and clinical studies have suggested that changes in the brain when someone stops drinking excessively are responsible for memory deficits. Excess of the stress hormones known as glucocorticoids is known to result in damage to nerves in the brain and to result in memory loss, and these are released in high concentrations during alcohol detoxification. Work has also shown that a drug, mifepristone, that prevents actions of the important stress hormone cortisol on a particular brain protein, known as the Type II glucocorticoid receptor, has beneficial effects in those who suffer from memory problems and also in people who are clinically depressed, but this has not yet been studied in alcoholics. Laboratory studies, however, demonstrated that prevention of actions of cortisol at this receptor protein decreases the nerve damage caused by cessation of long term alcohol consumption. This project will measure the effects of the drug mifepristone in a group of alcoholics who enter the treatment unit to undergo alcohol detoxification. Measures will be made of performance in tests of cognitive ability, and also depressive symptoms, since the latter can contribute to memory loss. If the results of this project are positive it will suggest that the receptor protein is involved in the genesis of the memory deficits and/or the depressive symptoms. Such knowledge will aid the development of new treatments that would provide effective therapy for these problems that are suffered by large numbers of alcoholics.