Neurodevelopmental Correlates of Reward Processing and Adolescent Substance Abuse

描述（由申请人提供）：药物滥用是一种影响数百万美国人的毁灭性疾病。这种疾病的经济和人际影响是巨大的。那些在早期就面临逆境的人滥用药物的风险更大，但我们对导致这种脆弱性的机制知之甚少。这项研究计划以青少年为重点，将描述参与奖励和决策过程的大脑系统的发展。尽管儿童和青少年时期的行为发生了戏剧性的变化，并增加了对药物的实验，但人们对这段时间内药物使用，滥用和脆弱性的神经生物学相关性知之甚少。对药物滥用人群的研究表明，决策和奖励过程发生了变化。本申请中提出的研究旨在通过研究早期逆境如何影响奖励和决策过程来阐明更多关于这些联系的内容。奖励敏感性和延迟奖励的能力将使用功能性磁共振成像进行检查。一个修改后的赌博任务也将被用来行为探测决策的风险青少年。这一提议的独特之处在于，大量的努力集中在1）控制潜在的重要神经心理学差异和2）更异质地定义风险。通过采用生活压力访谈，一个半结构化的访谈，我们的目的是更准确地探讨主观和客观方面的早期压力遭受。我们假设，早期的逆境，如虐待或贫困，可能会影响重要的大脑结构，如前额叶皮层和脑桥核，导致奖励处理和决策的异常模式。通过使用情感神经科学和发展心理病理学的工具，我们的目标是揭示早期逆境如何可能有助于药物滥用的脆弱性，并为高危儿童制定有效的治疗方案提供信息。 流行病学统计数据显示，美国近1350万儿童和青少年面临早期逆境，如极端贫困或虐待儿童。了解这些经历所传达的神经生物学脆弱性对公共卫生治疗和干预至关重要。此外，那些在发育早期遭受压力的人往往会使用和滥用更多的药物，频率也更高。了解脆弱性的这些方面可能对公共卫生预防和干预工作产生重大影响。此外，调查易受药物滥用的风险样本可能对理解药物滥用的一般发展轨迹有独特的见解。

DESCRIPTION (provided by applicant): Substance abuse is a devastating disorder that affects millions of Americans. The economic and interpersonal impact of this disease is immense. Those who have faced early adversity are at increased risk for substance abuse, yet we know little about the mechanisms that contribute to this vulnerability. This research proposal, focused on adolescence, will characterize the development of brain systems involved in reward and decision-making processes. Despite dramatic behavioral changes and increased experimentation with drugs during childhood and adolescence, little is known the neurobiological correlates of substance use, abuse, and vulnerability during this time. Research in substance abusing populations indicates changes in decision-making and reward processing. The research proposed in this application is designed to illuminate more regarding these connections by examining how early adversity impacts reward and decision-making processes. Reward sensitivity and the ability to delay reward will be examined using functional magnetic resonance imaging. A modified gambling task will also be used to behaviorally probe decision-making in at-risk adolescents. Unique to this proposal, great effort has been focused on 1) controlling for potentially important neuropsychological differences and 2) defining risk more heterogeneously. By employing the Life-Stress Interview, a semi-structured interview, we aim to more accurately probe the subjective and objective aspects of early stress suffered. We hypothesize that early adversity, such as maltreatment or poverty, may affect important brain structures such as the prefrontal cortex and the nucleus accumbens, causing aberrant patterns in reward processing and decision-making. By using the tools of affective neuroscience and developmental psychopathology, we aim to uncover how early adversity may contribute to the vulnerability for substance abuse and inform the development of effective treatment programs for at-risk children. Epidemiological statistics indicate that nearly 13.5 million children and adolescents in the US face early adversity, such as extreme poverty or child maltreatment. Understanding the neurobiological vulnerability conveyed by these experiences is crucial to public health treatment and interventions. Those who have suffered stress early in development in addition tend to use and abuse more drugs and with greater frequency. Understanding these facets of vulnerability could have major impacts on public health prevention and intervention efforts. In addition, investigating vulnerability to substance abuse in at-risk samples could have unique insights on understanding the general developmental trajectory of substance abuse.