Long-Term Abstinence Clinical Issues and CNS Disinhibition

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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.