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）决策障碍和某个区域的灰质体积减少（杏仁核）与神经学样本中的决策障碍有关，3）视觉P300振幅降低和延迟延迟，4）精神障碍的寿命和当前患病率增加，这表明酗酒者在面对持续的精神障碍时可以实现并保持长期的戒酒，5）主要由亚诊断症状和心理测量异常评分组成的大量共病精神疾病，6）LTAA与正常对照相比，即使排除了终生或目前有精神病诊断的个体，7）尽管有异常倾向、冲动和决策能力差的证据，但目前反社会人格障碍的症状是最小的，8）最近的数据表明，与对照组相比，LTAAs减少了皮质灰质体积。拟议研究的目标是在更大的样本中复制和扩展上述发现，将研究扩展到包括患有共病SUD的个体，这些个体在认知恢复、共病精神障碍和去抑制脑系统功能方面可能与没有共病SUD的LTAA有很大差异。我们已经修改了精神症状评估程序，以获得一个更清晰的图片正在进行的精神疾病和长期禁欲的ASPD症状的变化。最后，我们还将研究禁欲最初几个月的个体。拟议研究的一个焦点是，外化疾病的神经生物学去抑制基础是否随着禁欲而改变，或者易感性是否没有改变，但被更高的认知功能所掩盖。对早期戒断个体的研究将使我们能够比较长期戒断与早期戒断，以了解是否有迹象表明，长期戒断与最初几个月戒断的去抑制功能不同。公共卫生相关性本项目将研究长期戒酒者，以复制和扩展我们早期的研究结果，包括认知恢复，共病精神障碍和去抑制/外化连续体的神经生物学基础，包括这些现象是否，如何以及在多大程度上被修改长期戒酒。这项工作的一个主要扩展将是研究单独酒精依赖与酒精依赖和其他物质依赖的样本。这项研究将有助于阐明长期禁欲的临床和神经生物学特征.我们认为这些数据是必不可少的。只有通过了解具有显著并发症的治疗样本在处理慢性酒精中毒方面的成功，社会才能在未来促进这种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.