Neuronal Risk Markers for Nicotine Dependence in Youth

青少年尼古丁依赖的神经元风险标记

• 批准号: 7020681
• 负责人: UMA RAO
• 金额: $ 34.28万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7020681
• 关键词: adolescence (12-20); behavioral /social science research tag; biomarker; brain morphology; clinical research; cognition; craving; disease /disorder proneness /risk; drug addiction; frontal lobe /cortex; functional magnetic resonance imaging; handedness; human subject; hypothalamic pituitary adrenal axis; interview; limbic system; longitudinal human study; major depression; motivation; neurophysiology; neuropsychology; neurotoxicology; nicotine; reinforcer; smoking; tobacco abuse

DESCRIPTION (provided by applicant): This application is in response to RFA: DA-04-002 "Neuroimaging the Effects of Drugs of Abuse on the Development of the Human Nervous System". Cigarette smoking is a major public health problem that most often begins in adolescence and has a variety of serious negative consequences. Studies in animals and humans suggest that prolonged tobacco use causes neuroadaptation that accompanies the transition from use to dependence. Evidence also suggests that adolescent use of nicotine and other drugs of abuse may induce stronger effects on the systems sub-serving plasticity and cognition than in adults, consequently leading to more severe dependence-related behaviors. However, there are no clinical studies that have systematically examined this issue in youngsters. This proposal seeks to identify characteristics of brain function that can predict the risk for development of nicotine dependence (ND) in adolescents. It employs a prospective design and utilizes functional magnetic resonance imaging (fMRI) to identify possible abnormalities in the reactivity of specific brain regions to cognitive challenges in youth at high- and low-risk for ND. We hypothesize that altered responsivity of the brain circuits involved in motivational-reward processes to cognitive stimuli will be related to the development of ND in a longitudinal study and that the observed brain changes are more prominent in the high-risk group. The adolescents also will participate in follow-up studies of fMRI studies (after the onset of ND in those who develop it) to determine if, and to what extent, changes in brain function occur as a consequence of ND by comparing the baseline and follow-up measurements. The longitudinal design will distinguish pre-existing vulnerability markers for smoking and ND from changes in brain function due to chronic smoking. Distinction between premorbid factors and sequelae has implications for primary prevention and treatment programs. The high-risk group will consist of adolescents with depression, and the low-risk group will be comprised of youth without psychiatric illness. Studies in adolescents and adults have indicated that depression increases the risk for smoking. Also, data from adults suggest that depressed patients have more severe ND than their non-depressed counterparts, and a tendency for greater difficulty with smoking cessation and increased risk for relapse of depressive episodes during attempts to quit. The underlying mechanisms linking these two disorders are not well understood, thereby limiting the development of effective treatments. A systematic examination of the inter-relationships between depression and brain responsivity and the association of these two entities with vulnerability for ND and clinical course of depression will aid in the development of evidence-based algorithms for the diagnosis and treatment of individual patients with these disorders.

描述（由申请人提供）： 本申请是对RFA：DA-04-002“滥用药物对人类神经系统发育影响的神经成像”的回应。吸烟是一个主要的公共卫生问题，通常始于青春期，并产生各种严重的负面后果。对动物和人类的研究表明，长期使用烟草会导致伴随着从使用到依赖的过渡的神经适应。证据还表明，青少年使用尼古丁和其他滥用药物可能会对可塑性和认知系统产生比成年人更强的影响，从而导致更严重的依赖相关行为。然而，没有临床研究系统地研究了青少年的这个问题。 该提案旨在确定可以预测青少年尼古丁依赖（ND）发展风险的大脑功能特征。它采用了前瞻性设计，并利用功能性磁共振成像（fMRI），以确定在特定的大脑区域的反应可能异常的认知挑战的青年在高风险和低风险的ND。我们假设，在一项纵向研究中，参与动机-奖励过程的大脑回路对认知刺激的反应性改变与ND的发展有关，并且观察到的大脑变化在高危人群中更为突出。青少年还将参加fMRI研究的后续研究（在发生ND的人中发病后），以通过比较基线和随访测量结果来确定ND是否以及在多大程度上导致脑功能变化。纵向设计将区分吸烟和ND的预先存在的脆弱性标志物与慢性吸烟引起的脑功能变化。发病前因素和后遗症之间的区别对一级预防和治疗方案有影响。 高风险群体将由患有抑郁症的青少年组成，低风险群体将由没有精神疾病的青年组成。对青少年和成年人的研究表明，抑郁症会增加吸烟的风险。此外，来自成年人的数据表明，抑郁症患者比非抑郁症患者有更严重的ND，并且在尝试戒烟期间戒烟困难更大，抑郁发作复发的风险增加。连接这两种疾病的潜在机制尚未得到很好的理解，从而限制了有效治疗的发展。抑郁症和脑反应性之间的相互关系和这两个实体与ND的脆弱性和抑郁症的临床过程的关联的系统检查将有助于发展基于证据的算法，用于诊断和治疗患有这些疾病的个体患者。