Long-Term Abstinence Clinical Issues and CNS Disinhibition

描述(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(LTAA)。这些研究的数据是独一无二的，具有潜在的重要意义。我们发现：1)认知功能基本正常，2)神经样本中与决策障碍有关的区域(杏仁核)的决策障碍和灰质体积减少，3)视觉P300波幅降低和潜伏期延迟，4)精神障碍的终生和当前患病率增加，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酒，5)主要由亚诊断症状和心理测量异常分数组成的实质性共病精神疾病，6)与正常对照组相比，LTA患者更严重的合并精神障碍，即使排除了一生或当前精神诊断的个人，7)尽管有越轨倾向、冲动和糟糕的决策的证据，但目前反社会人格障碍的症状是轻微的，以及8)最近的数据显示，与对照组相比，LTAA组的皮质灰质体积减少了。这项拟议研究的目标是在更大的样本中复制和扩展上述发现，将研究扩大到患有肥皂水的个体，这些人在认知恢复、合并精神障碍和去抑制大脑系统的功能方面可能与没有合并肥皂水的LTAA有很大不同。我们已经修改了精神症状评估程序，以便更清楚地了解持续的精神疾病和长期戒酒后ASPD症状的变化。最后，我们还将研究禁欲最初几个月的个体。这项拟议的研究的一个重点是，外在性疾病的神经生物学抑制基础是否随着禁欲的改变而改变，或者易感性是否没有变化，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将长期禁欲与早期禁欲进行比较，看看是否有迹象表明，长期禁欲与最初几个月的禁欲具有不同的去抑制功能。公共卫生研究这个项目将研究长期戒酒的人，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发现，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仅有酒精依赖的样本与酒精依赖和其他物质依赖的样本。拟议中的研究应该有助于阐明长期禁欲的临床和神经生物学图景。我们认为这样的数据是必不可少的。只有通过了解在患有严重共病的治疗样本中处理慢性酒精中毒的成功，社会才能在促进未来取得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.