A risk factor analysis of human brain states related to development of addiction

与成瘾发展相关的人脑状态的危险因素分析

• 批准号: 8725333
• 负责人: Clinton D Kilts
• 金额: $ 35.15万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725333
• 关键词: Adherence; Adolescence; Adolescent; Adult; Affect; Animal Model; Behavior; Behavior Control; Behavioral; Biological Markers; Brain; Classification; Cross-Sectional Studies; Development; Disease; Drug Addiction; Drug Use Disorder; Drug abuse; Drug usage; Early-life trauma; Effectiveness; Exploratory/Developmental Grant; Exposure to; Factor Analysis; Female Adolescents; Functional Magnetic Resonance Imaging; Goals; Human; Human Development; Image; Impulsivity; Individual; Intervention; Life; Life Stress; Link; Mediating; Mental Depression; Modeling; Neurobiology; Neurosciences; Pathway interactions; Pattern; Personality Traits; Pharmaceutical Preparations; Post-Traumatic Stress Disorders; Process; Psychological reinforcement; Psychophysiology; Recording of previous events; Relapse; Research Design; Rewards; Risk; Risk Factors; Sampling; Signal Transduction; Staging; Stress; Testing; Trauma; Woman; Work; addiction; assault; biological adaptation to stress; design; discounting; dysphoria; effective intervention; girls; maltreatment; mental imagery; neural information processing; neurobiological mechanism; non-drug; pediatric trauma; prevent; public health relevance; relating to nervous system; response; trait; young adult

Abstract The chronically relapsing disorder of drug addiction is the product of behavior and brain state transitions as impulsive drug use escalates to compulsive drug abuse. These transition states are well informed by animal models though their human representations are not known. In this revised proposal, we propose to define the human neurobiological mechanisms of transition to drug addiction by characterizing the impact and interaction effects for three putative addiction risk factors: the developmental period of adolescence, exposure to early life trauma, and the presence of potentially problematic drug abuse. Four specific aims are proposed to test project hypotheses. A conceptual model would be tested in which the impact of early trauma on two intermediate personality traits involving negative (reactivity to stress, Aim 1) and positive (impulsivity, Aim 2) behavioral reinforcement processes mediates the heightened risk for transition from impulsive to compulsive drug use. These two traits are central to behavioral reinforcement models of compulsive drug abuse in which relief of stress or dysphoria reinforces drug use and impulsivity or deficits in inhibitory behavioral control reinforces drug use. Both traits are also heightened by early life stress. Groups of adolescent girls differing in having potentially problematic drug use (-/+) or trauma exposure histories (-/+), but not fulfilling syndromal criteria for drug dependence, PTSD or depression, would be compared by task- related functional magnetic resonance imaging (fMRI) responses. Further cross-sectional comparisons would determine whether risk for development of addiction shares a neural correlate of addiction processes with drug-dependent adults (Aim 3). Multivariate, individual-level analyses using fMRI pattern classification and prediction approaches would seek neurobiological explanations of addiction transition risk in the form of altered functional organization of neural information processing networks for the candidate reinforcement processes (Aim 4). The proposed cross-sectional study design would test an overall hypothesis that trauma exposure predisposes affected individuals towards drug use disorders by altering the brain maturation of two behavioral reinforcement processes linked to drug addiction risk: stress reactivity and impulsivity.

摘要 药物成瘾的慢性复发性障碍是行为和大脑状态转换的产物， 冲动性吸毒升级为强迫性吸毒。这些过渡状态是由动物 模型，虽然他们的人类代表是未知的。在本修订建议中，我们建议界定 人类神经生物学机制的过渡到药物成瘾的特点的影响和 三个假定的成瘾风险因素的相互作用：青春期的发育期， 暴露于早期生活创伤，以及存在潜在的问题药物滥用。四个具体目标是 测试项目假设。一个概念模型将被测试，其中早期创伤的影响 两个中间的人格特质，包括消极的（对压力的反应，目标1）和积极的（冲动， 目的2）行为强化过程介导了从冲动到冲动的转变的高风险。 强迫性吸毒这两个特征是强迫性药物行为强化模型的核心 缓解压力或烦躁不安的滥用会加强药物使用和冲动或抑制功能的缺陷 行为控制强化了药物使用。这两种特征也会因早年生活压力而加剧。组 不同的青春期女孩有潜在的问题药物使用（-/+）或创伤暴露史（-/+）， 但不符合药物依赖，创伤后应激障碍或抑郁症的综合征标准，将通过任务进行比较- 相关的功能性磁共振成像（fMRI）反应。进一步的横向比较将 确定成瘾发展的风险是否与成瘾过程的神经相关， 药物依赖成人（目标3）。使用fMRI模式分类的多变量个体水平分析， 预测方法将寻求成瘾过渡风险的神经生物学解释，其形式为 候选强化的神经信息处理网络的改变的功能组织 过程（目标4）。拟议的横断面研究设计将测试一个总体假设，即创伤 暴露易使受影响的个人对药物使用障碍，通过改变大脑成熟的两个 与药物成瘾风险相关的行为强化过程：压力反应和冲动。