Mechanisms Relating Conduct Disorder and Drug Abuse

说明(由申请人提供)：根据NIDA/NIMH RFA(DA-03-007)，本提案正通过R21机制提交供资金审议。这项研究的主要目的是在高危青少年男女样本中确定与行为障碍(CD)和药物使用有关的生物行为机制。为此，将使用结构方程模型的横断面设计来检查情绪反应性缺陷和额叶-边缘功能障碍的生理和行为指标在多大程度上解释行为症状和药物问题之间的关系。这些变量的重要性将与行为问题和药物使用共同存在的既定环境风险因素结合起来进行权衡。我们将在少年教养所检查总共250名青少年男性和女性。我们正在进行的工作表明，与从其他环境招募的青年相比，这一群体中的行为问题和毒品参与范围更广。这一人群中广泛的反社会行为和药物使用将允许对CD症状与毒品问题之间的机制进行更有力的测试。情绪反应性和额叶-边缘功能的外周表达将使用以下三个指标进行评估：(1)应激激素皮质醇的变化，(2)情绪调节的惊吓范式，以及(3)Bechara赌博任务的表现，这是一个既定的客观实验室任务，旨在捕捉额叶-边缘区域控制的特定类型的加工。我们认为，品行问题，特别是青春期之前和药物使用前出现的问题，可能是潜在的额叶-边缘功能障碍的标志。这种潜在的功能障碍可能在一定程度上解释了为什么行为问题的儿童特别容易在以后出现药物使用障碍。额叶-边缘功能障碍相关行为问题的发现可能导致药物滥用，这将为这些疾病的常见生物行为病因提供见解，并为改进预防和治疗努力指明方向。

DESCRIPTION (provided by applicant): This proposal is being submitted for funding consideration through the R21 mechanism in response to the NIDA/NIMH RFA (DA-03-007). The major purpose of this study is to identify biobehavioral mechanisms relating conduct disorder (CD) and drug use among a sample of high risk adolescent males and females. To this end, a cross-sectional design using structural equation modeling will be used to examine the extent to which physiologic and behavioral indices of deficient emotional reactivity and frontal-limbic dysfunction account for the relationship between conduct symptoms and drug problems. The significance of these variables will be weighed in combination with established environmental risk factors common to both conduct problems and drug use. We will examine a total of 250 adolescent males and females at a juvenile correctional facility. Our ongoing work indicates a broader range of conduct problems and drug involvement in this population relative to youth recruited from other settings. The broad spectrum of antisocial behavior and substance use in this population will allow for a more robust test of mechanisms relating CD symptoms with drug problems. Peripheral expression of emotional reactivity and frontal-limbic function will be assessed using the following three indicators: (1) changes in the stress hormone cortisol, (2) emotion-modulated startle paradigm, and (3) performance on the Bechara Gambling Task, an established objective laboratory task designed to capture the particular kinds of processing governed by frontal-Iimbic regions. We believe that conduct problems, especially those that occur prior to adolescence and to substance use, may be a marker for underlying frontal-limbic dysfunction. This underlying dysfunction may, in part, explain why children with conduct problems are especially prone to later substance use disorders. A finding of frontal-limbic dysfunction associated conduct problems that confers liability for drug misuse would provide insights into common biobehavioral etiologic factors of these disorders and point the way toward improved prevention and treatment efforts.