Brain Morbidity in Treatment-Naive Alcoholics

描述（由申请人提供）：在前五年的工作中，我们表明，对接受治疗的酗酒者的便利样本的研究体现了一种偏见，称为“Berkson's Fallacy”，即接受治疗的AD患者与普通人群中未接受过治疗的AD患者不同，后者构成了大多数酗酒者。我们研究了21-50岁的主动饮酒治疗初治AD（TNAD）和年龄和性别相当的对照组，并将其与我们正在进行的长期戒酒治疗AD（ATAD）研究进行比较。我们发现，在开始酗酒后的初始阶段，酒精摄入量，TNAD不只是治疗AD观察早期的疾病进展，而是包括一个亚群与较低的初始重型酒精消费比ATAD。关于精神共病，我们发现TNAD组比非酒精对照组（NAC）有更多的精神障碍，但比ATAD组精神障碍少。我们还发现，TNAD在MRI上比ATAD有更多的正常大脑结构，并且尽管有大量饮酒，TNAD在认知上是正常的。在目前的建议中，我们将研究35- 60岁的TNAD，他们中的大多数人会比我们以前的TNAD更长时间地酗酒（并且一生的酒精摄入量要高得多）。本研究的主要目的是：1）确定35-60岁TNAD与年龄相当的NAC以及短期和长期ATAD在脑结构和功能方面是否存在差异（可从我们的待定项目中获得）; 2）确定35-60岁的TNAD是否与NAC以及短期和长期ATAD在共病情绪，焦虑，和外化障碍诊断、症状和特征; 3）确定与TNAD中脑结构和功能损伤相关的因素（包括共病情绪、焦虑和外化障碍诊断的存在和严重程度、症状和特征、作为功能储备量度的病前脑大小（如通过MRI上的颅内穹窿体积所指示的）、饮酒的模式和严重程度，戒断症状的频率（包括严重程度）和诱发因素，如酒精问题的家族史或电生理学和行为最终表型酒精中毒标志物）; 4）确定男性和女性在这些比较中是否不同;和5）确定伴随药物滥用/依赖对这些比较的影响。公共卫生相关性我们以前已经表明，30岁的治疗初治酒精依赖者是非酒精控制和治疗酗酒者之间的中间。在目前的提案中，我们计划继续这项工作，研究35 - 60岁的治疗初治酒精依赖者。这些人应该有一个更大的终身酒精负担比以前研究的30岁的样本。此外，我们纳入了初治药物和酒精依赖个体的样本，以提供对美国人群更大的普遍性，并检验以下假设：伴随药物依赖与更严重的AD、更严重的精神合并症以及更严重的认知和脑结构发病率相关。这些中年TNAD占所有酗酒者的40%左右，绝大多数从未寻求治疗。由于美国大多数关于酗酒的研究都使用了治疗中的酗酒者（所有酗酒者中的少数）的便利样本，因此拟议的研究对于了解AD对美国人口的影响至关重要。

DESCRIPTION (provided by applicant): In the first five years of work, we showed that the study of convenience samples of treated alcoholics embody a bias, called `Berkson's Fallacy', in that treated individuals with AD differ from treatment naive individuals with AD in the general population, who comprise the majority of alcoholics. We studied 21-50 year old actively drinking treatment naive AD (TNAD) and age and gender comparable controls, and compared them to our other ongoing study of long-term abstinent treated AD (ATAD). We showed that with regard to alcohol intake in the initial period after starting abusive drinking, TNAD were not simply treated AD observed earlier in the progression of the disease, but rather comprise a subpopulation with lower initial heavy alcohol consumption than ATAD. Regarding psychiatric comorbidity, we showed that TNAD had more psychiatric disorder than non-alcoholic controls (NAC), but less psychiatric disorder that ATAD. We also showed that TNAD have more normal brain structure on MRI than ATAD, and that TNAD are cognitively normal despite active heavy drinking. In the current proposal, we will study TNAD 35--60 years of age, most of whom would have drank abusively for longer periods (and have a much higher total lifetime alcohol intake) than our former TNAD. The major goals of the proposed research are: 1) to determine whether 35-60 year old TNAD differ in brain structure and function from age-comparable NAC, and from both short- and long-term ATAD (to be available from our pending project); 2) to determine whether 35-60 year old TNAD differ from NAC and from both short- and long-term ATAD in the presence and severity of comorbid mood, anxiety, and externalizing disorder diagnoses, symptoms and traits; 3) to determine the factors associated with impairments in brain structure and function in TNAD (including presence and severity of comorbid mood, anxiety, and externalizing disorder diagnoses, symptoms and traits, premorbid brain size as a measure of functional reserve (as indexed by intracranial vault volume on MRI), the pattern and severity of drinking, the frequency of withdrawal symptoms (including severity), and predisposing factors such as the family history of alcohol problems or electrophysiological and behavioral end phenotypic alcoholism markers)); 4) to determine whether men and women differ in these comparisons; and 5) to determine the effect of concomitant drug abuse/dependence on these comparisons. PUBLIC HEALTH RELEVANCE We have previously shown that 30-year old treatment-naive alcohol dependent individuals are intermediate between non-alcoholic controls and treated alcoholics. In the current proposal, we plan to continue this work, studying 35 - 60 year old treatment naive alcohol dependent individuals. Such individuals should have a much greater lifetime alcohol burden than the 30 year old samples studied previously. Additionally, we are including a sample of treatment-naive drug and alcohol dependent individuals, to provide greater generalizabilty to the U.S. population, and test the hypothesis that concomitant drug dependence is associated with more severe AD, greater psychiatric comorbidity, and greater cognitive and brain structural morbidity in treatment naive AD. These middle-aged TNAD comprise about 40% of all alcoholics, and the great majority never seek treatment. Since most studies of alcoholism in the U.S. use convenience samples of alcoholics in treatment (a minority of all alcoholics), the proposed studies are essential to understand the impact of AD on the US population.