Interoceptive Dysregulation in Adolescents At Risk for Substance Dependence

项目1：青少年使用苯丙胺类药物是一个重大的公共卫生问题， 老年人使用甲基苯丙胺或非处方的药用苯丙胺 （MTF，2008）。内感受是指通过传入纤维感知和处理体内状态， 整合在岛叶皮层中。先前的研究已经将岛叶皮层功能 成瘾的各个方面。然而，内感受系统和岛叶皮层在脑内的确切作用还不清楚。 药物依赖的发展尚不清楚。在这里，我们假设岛叶皮层反应迟钝 对内感受性刺激，但对有物质风险的青少年的药物线索反应过度 依赖性是基于青年时期的反复实验。在这个项目中，我们将比较 内感受性系统对正、负效价内感受性和药物线索刺激的反应 之间：（1）处于危险之中的青少年谁是目前使用安非他明，（2）弹性青少年谁是 曾经使用过安非他明，但在没有达到依赖性标准的情况下停止使用，和（3）控制 没有安非他明使用史的青少年。其目的是：（1）确定企业的作用， 处理内感受性信息的青少年在安非他明依赖的风险，青少年谁出现 对苯丙胺依赖有弹性的青少年和健康对照青少年;（2）确定 有苯丙胺依赖风险的青少年在处理线索相关信息时的反应， 对苯丙胺依赖有弹性的青少年和健康对照青少年;（3）修改神经影像学 响应项目3（动物研究）的范例，以更好地表征内感受回路在 在有安非他明风险的青少年中，直接的正（高）与负（戒断/宿醉）效应 依赖性;（4）通过比较，研究青少年内感受系统的发展 青少年对照组和成人对照组（来自项目2）对内感受性和药物线索的激活模式 任务总之，这些研究将有助于确定内感受性失调如何在将 有使用安非他明风险的青少年。这些见解将用于未来的研究，旨在改变 岛叶皮层的反应性作为预防或治疗物质依赖的一种方式。组合结果 从项目1和2将产生重要的见解岛叶皮层和interocepfive的作用， 一般都有依赖安非他明的风险。最后，这项研究的结果将使我们做好准备， 在本中心的P50扩展中进行内感受性功能障碍的纵向研究。

Project 1: Adolescents' use of amphetamine drugs is a major public health concern, as 11% of high school seniors have used methamphetamine or a pharmaceufical amphetamine taken other than for prescribed purposes (MTF, 2008). Interoception refers to sensing and processing the internal body state via afferent Cfibers, which is integrated in the insular cortex. Previous invesfigafions have linked insular cortex functioning to aspects of addiction. However, the precise role of the interoceptive system and insular cortex in the development of substance dependence is unclear. Here, we hypothesize that the insular cortex is hyporesponsive to interoceptive stimulation, but hyper-reactive to drug cues in adolescents at risk for substance dependence based on repeated experimentation during youth. In this project, we will compare activity of the interoceptive system in response to positively and negatively valenced interoceptive and drug cue stimuli between: (1) at-risk adolescents who are current users of amphetamines, (2) resilient adolescents who are former users of amphetamines but stopped without ever meeting dependence criteria, and (3) control adolescents with no history of amphetamines use. The aims are: (1) to determine the role of the insula in processing interoceptive information in teens at risk for amphetamine dependence, teens who appear resilient to amphetamine dependence, and healthy control adolescents; (2) to determine the role of the insula in processing cue-related informafion in teens at risk for amphetamine dependence, teens who have been resilient to amphetamine dependence, and healthy control adolescents; (3) to modify neuroimaging paradigms in response to Project 3 (animal studies) to better characterize the role of interoceptive circuitry in the direct posifive (high) versus negafive (withdrawal/hangover) effects among teens at risk for amphetamine dependence; and (4) examine the development of the interoceptive system in adolescence by comparing adolescent controls and adult controls (from Project 2) on activation patterns to interoceptive and drug cue tasks. Together, these studies will help determine how interoceptive dysregulation plays a role in putting adolescents at risk for amphetamine use. These insights will be used in future studies aimed at altering the reactivity of the insular cortex as a way of preventing or treating substance dependence. Combining results from Projects 1 and 2 will yield important insights into the role of the insular cortex and interocepfive functioning in risk for amphetamine dependence in general. Finally, the outcome of this study will prepare us for longitudinal studies of interoceptive dysfunction in a P50 extension of this Center.