Markers of Risk for Nicotine Dependence in Youngsters

青少年尼古丁依赖的风险标志

• 批准号: 6424690
• 负责人: UMA RAO
• 金额: $ 38.23万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6424690
• 关键词: adolescence (12-20); behavioral /social science research tag; biomarker; blood tests; clinical research; comorbidity; cortisol; depression; developmental psychology; disease /disorder proneness /risk; hormone regulation /control mechanism; human subject; hypothalamic pituitary adrenal axis; interview; longitudinal human study; neuropsychology; nicotine; public health; saliva; smoking; substance abuse epidemiology; substance abuse related behavior; tobacco abuse; tobacco abuse prevention

DESCRIPTION (provided by applicant): Cigarette smoking in adolescents is a major public health problem, which not only relates to the younger population, but also for the long-term physical and mental health of adults. Studies suggest that most adults could be prevented from becoming tobacco users if they could be kept tobacco-free during adolescence. However, not all youth who begin smoking develop nicotine dependence (ND). In order for the prevention efforts for smoking to be most effective, it is important to elucidate the underlying mechanisms that drive the progression to ND, as well as to gain a better understanding of the individual differences in vulnerability. Data from diverse lines of research suggest a close connection between depression and ND. However, the mechanisms underlying the linkages between these two disorders are poorly understood, thereby limiting the development of effective treatments. Studies in both humans and animals suggest that the stress-response system may be involved in both ND and depressive disorder. Using a longitudinal design, this investigation seeks to examine the association between hypothalamic-pituitary-adrenal (HPA) dysregulation and risk for smoking initiation and progression to ND in four groups of adolescents: (1) depressed adolescents with no previous or current tobacco use; (2) depressed adolescents with current tobacco use; (3) normal adolescents with no previous or current tobacco use; and (4) normal adolescents with current tobacco use. Pilot data from our laboratory have shown that elevated cortisol near bedtime increases the risk for non-nicotine substance-related disorders and for recurrent depressive episodes in depressed adolescents. Other data suggest that antidepressant (AD) agents are helpful in reducing nicotine/other substance use in addition to improving depressive symptoms, which might be due to down-regulation of the HPA axis by the AD drugs. If our preliminary results, showing a relationship between high cortisol and risk for substance use disorders, are extended to ND, the findings potentially might be helpful in identifying the subgroup of youth with these disorders who might benefit most from AD or anti-glucocorticoid treatment strategies. This would have important clinical implications because, as a group, youngsters tend to show more variability in AD response compared with adult depressed patients. More focused and effective interventions early in the course of the disorder might be helpful in reducing the long-term morbidity and mortality associated with ND. Even if only a small subgroup of youngsters at risk for ND can be identified by such means, because of the many direct as well as indirect negative consequences associated with ND, this will be of great public health importance.

描述（由申请人提供）：青少年吸烟是一种 主要的公共卫生问题，这不仅关系到年轻人口， 也是为了成年人的长期身心健康。研究 这表明，大多数成年人可以避免成为烟草使用者，如果他们 在青少年时期不吸烟。然而，并不是所有开始 吸烟会产生尼古丁依赖（ND）。为了预防 为了使吸烟最有效，重要的是要阐明潜在的 驱动ND进展的机制，以及获得更好的 了解脆弱性的个体差异。数据来自不同的 一系列的研究表明抑郁症和ND之间有密切的联系。 然而，这两种疾病之间联系的机制是 人们对此知之甚少，从而限制了有效治疗方法的发展。 对人类和动物的研究表明，压力反应系统可能 既有神经衰弱又有抑郁症采用纵向设计， 这项调查旨在研究 下丘脑-垂体-肾上腺（HPA）失调与吸烟风险 在四组青少年中开始和进展到ND：（1）抑郁 既往或当前未吸烟的青少年;（2）抑郁青少年 （3）正常青少年，无既往或当前吸烟史 烟草使用;（4）目前吸烟的正常青少年。导频数据 我们实验室的研究表明， 非尼古丁物质相关疾病和复发性 抑郁青少年的抑郁发作。其他数据表明， 抗抑郁药（AD）有助于减少尼古丁/其他物质的使用 除了改善抑郁症状，这可能是由于 通过AD药物下调HPA轴。如果我们的初步结果， 显示高皮质醇和物质使用风险之间的关系 疾病，扩展到ND，研究结果可能有助于 确定患有这些疾病的青年亚组， 或抗糖皮质激素治疗策略。这将对 临床意义，因为作为一个群体，年轻人往往表现出更多的 与成年抑郁症患者相比，AD反应的变异性。更专注 在疾病早期进行有效的干预 有助于降低与ND相关的长期发病率和死亡率。 即使只有一小部分有ND风险的青少年可以通过以下方法确定， 由于许多直接和间接的负面影响， 与ND相关的后果，这将是伟大的公共卫生 重要性