Brain Morbidity in Treatment-Naive Alcoholics

描述（由申请人提供）：大多数关于酒精影响的研究 对大脑的依赖性已经检查了治疗中的个体。它们可能体现了 一种偏见，叫做“伯克森？S谬误”，如果变量之间的关联（例如， 酒精中毒和脑萎缩或脑功能）在人群之间存在差异 治疗中的酗酒者和一般人群中的酗酒者。我们 假设未接受过治疗的酗酒者有较少的精神共病 与治疗样本相比，精神病发病率的降低是 与大脑结构损伤的严重程度减轻有关， 功能 本研究的主要目的是确定：（1）是否 未经治疗的酗酒者在大脑结构和功能上与 从治疗中心招募的酗酒者，2）是否未经治疗 酗酒者与从治疗中心招募的酗酒者不同， 共病情绪和外化障碍症状的存在和严重程度， 特征，3）哪些因素与大脑结构的损伤有关， 在未接受过治疗的酗酒者和接受过治疗的酗酒者中的作用 中心（包括共病情绪、焦虑和 外化障碍症状和特征，APOE-4等位基因的存在， 发病前头部大小作为功能储备的衡量标准（如指数 MRI上的颅内穹窿体积），以及 戒断症状），4）男性和女性在这些比较中是否不同， 和5）跟踪未治疗的酗酒者， 评估预测他们酗酒过程的因素（特别是 寻求治疗，以及大脑结构和功能的变化）。 我们将在五年内研究380名受试者：220名未经治疗的受试者 酒精依赖受试者，80例门诊酒精依赖受试者 治疗组和80个终生光照/非饮酒者对照组。处理试样 将从门诊治疗中心抽取。初治样本 将从马林县第一次犯罪饮酒司机（FODD）招募 程序.将从社区招募轻度/不饮酒对照。 将使用MRI检查大脑结构，并将包括分割 大脑进入？组成组织分类，特定组织的描述 结构（例如，海马、小脑和胼胝体），以及 将图像变换到标准坐标系中（以便于 区域皮质体积差异的分析）。功能评估将 包括神经心理学和行为测试以及电生理学 记录，侧重于抑制/去抑制过程，执行 功能，视觉空间能力，步态和平衡，以及处理和记忆 情绪刺激的。

DESCRIPTION (provided by applicant): Most studies of the impact of alcohol dependence on the brain have examined individuals in treatment. They may embody a bias, called "Berkson?s fallacy", if the association between variables (e.g., alcoholism and brain atrophy or brain function) differ between the population of alcoholics in treatment and alcoholics in the general population. We hypothesize that treatment-naive alcoholics have less psychiatric comorbidity compared to treatment samples, and that this reduced psychiatric morbidity is associated with a lessened severity of impairments in brain structure and function. The major goals of the proposed research are to determine: 1) whether treatment-naive alcoholics differ in brain structure and function from alcoholics recruited from treatment centers, 2) whether treatment-naive alcoholics differ from alcoholics recruited from treatment centers in the presence and severity of comorbid mood and externalizing disorder symptoms and traits, 3) what factors are associated with impairments in brain structure and function in treatment-naive alcoholics and in alcoholics drawn from treatment centers (including presence and severity of comorbid mood, anxiety, and externalizing disorder symptoms and traits, presence of the APOE-4 allele, premorbid headsize as a measure of functional reserve (as indexed by intracranial vault volume on MRI), and the frequency (and severity) of withdrawal symptoms), 4) whether males and females differ in these comparisons, and 5) to follow the treatment-naive alcoholics for future longitudinal assessment of factors that predict the course of their alcoholism (especially the seeking of treatment, and changes in brain structure and function). We will study 380 subjects over five years: 220 treatment-naive alcohol-dependent subjects, 80 alcohol-dependent subjects in outpatient treatment, and 80 lifetime light/non-drinker controls. The treatment sample will be drawn from outpatient treatment centers. The treatment-naive sample will be recruited from the Marin County First Offender Drinking Driver (FODD) program. The light/non-drinker controls will be recruited from the community. Brain structure will be examined using MRI, and will include segmentation of the brain into its? component tissue classes, delineation of specific structures (e.g., the hippocampus, cerebellum, and corpus callosum), and transformation of the images into a standard coordinate system (to facilitate analysis of regional cortical volume differences). Functional assessment will include neuropsychological and behavioral testing and electrophysiological recordings, focusing on inhibitory/disinhibitory processes, executive functions, visuospatial abilities, gait and balance, and processing and memory of emotional stimuli.