Long-Term Abstinence Clinical Issues and CNS Disinhibition

描述（由申请人提供）：在过去的几年里，我们的实验室一直在研究长期戒酒者（LTAAs）。这些研究的数据是独特的，可能非常重要。我们发现：1)基本正常的认知功能，2)决策障碍和神经系统样本中与决策障碍有关的区域（杏仁核）的灰质体积减少，3)视觉P300振幅降低和延迟潜伏期，4)精神疾病的终生和当前患病率更高，这表明面对持续的精神疾病，酗酒者可以实现并保持长期戒断。5)主要由亚诊断症状和心理测量异常分数组成的严重共病性精神疾病；6)与正常对照相比，ltaa的共病性精神障碍更大，即使排除了终生或当前的精神诊断；7)反社会人格障碍的当前症状很小，尽管有证据表明存在偏差倾向、冲动和决策能力差；8)最近的数据表明，与对照组相比，ltaa的皮质灰质体积减少。拟议研究的目标是在更大的样本中复制和扩展上述发现，扩大研究范围，包括患有并发性sud的个体，这些个体在认知恢复、共病性精神障碍和去抑制性脑系统功能方面可能与没有并发性sud的LTAAs存在很大差异。我们修改了精神症状评估程序，以便更清楚地了解正在发生的精神疾病以及长期戒断后反社会人格障碍症状的变化。最后，我们还将研究戒酒最初几个月的个体。拟议研究的一个重点是，外化疾病的神经生物学去抑制基础是否随着禁欲而改变，或者这种倾向是否没有改变，但被更高的认知功能所掩盖。对早期禁欲个体的研究将使我们能够比较长期禁欲和早期禁欲，看看是否有迹象表明长期禁欲和最初几个月的禁欲的去抑制功能是不同的。本项目将研究长期戒酒的酗酒者，以复制和扩展我们早期关于认知恢复、共病精神障碍和去抑制/外化连续体的神经生物学基础的研究结果，包括这些现象在长期戒酒中是否、如何以及在多大程度上被改变。这项工作的一个主要扩展将是研究单独的酒精依赖与酒精依赖和其他物质依赖的样本。提出的研究应有助于阐明长期禁欲的临床和神经生物学图景。我们认为这些数据是必不可少的。只有了解在处理具有显著共病的治疗样本中的慢性酒精中毒的成功，社会才能够在促进此类成功方面取得重大进展。

DESCRIPTION (provided by applicant): Over the past years, our laboratory has been studying long-term abstinent alcoholics (LTAAs). The data from those studies are unique and of potential great importance. We have found: 1) essentially normal cognitive functioning, 2) decision- making impairments and reduced gray matter volumes in an area (the amygdala) implicated in decision making impairments in neurologic samples, 3) reduced visual P300 amplitudes and delayed latencies, 4) greater lifetime and current prevalence of psychiatric disorders, suggesting that alcoholics can achieve and maintain long-term abstinence in the face of an ongoing psychiatric disorder, 5) substantial comorbid psychiatric illness that consisted primarily of sub-diagnostic symptoms and abnormal scores on psychological measures, 6) greater comorbid psychiatric disturbance in LTAAs vs. normal controls, even if individuals with lifetime or current psychiatric diagnoses were excluded, 7) that current symptoms of Antisocial Personality Disorder were minimal despite evidence of deviance proneness, impulsivity and poor decision- making, and 8) very recent data that the LTAAs have reduced cortical gray matter volumes compared than controls. The goals of the proposed research are to replicate and extend the above findings in larger samples, expanding the studies to include individuals with comorbid SUDs, who may differ substantially from LTAAs without comorbid SUDs with regard to cognitive recovery, comorbid psychiatric disturbance, and the function of disinhibitory brain systems. We have modified the psychiatric symptom assessment procedure to obtain a much clearer picture of ongoing psychiatric illness and changes in ASPD symptoms with long-term abstinence. Finally, we will also study individuals in the very first months of abstinence. A focus of the proposed research is whether the neurobiological disinhibitory underpinnings of externalizing illness have changed with abstinence, or whether the predisposition is unchanged, but is kept under wraps by higher cognitive functions. The study of individuals in early abstinence will enable us to compare long-term abstinence with early abstinence to see if there are suggestions that disinhibitory function is different in long-term vs. the first months of abstinence. PUBLIC HEALTH RELEVANACE This project will examine long-term abstinent alcoholics to replicate and extend our earlier findings with regard to cognitive recovery, comorbid psychiatric disturbance, and the neurobiological underpinnings of the disinhibition/externalizing continuum, including whether, how, and to what extent these phenomena are modified in long-term abstinence. A major extension of the work will be to study samples with alcohol dependence alone vs. with alcohol dependence and other substance dependence. The proposed studies should help elucidate the clinical and neurobiological picture of long- term abstinence. We believe such data is essential. It is only by understanding the successes in dealing with chronic alcoholism among treated samples with significant comorbidity that society will be able to make significant progress in facilitating such successes in the future.