Markers of Risk for Nicotine Dependence in Youngsters

描述(申请人提供)：青少年吸烟是一个主要的公共健康问题，这不仅与年轻人口有关， 而且对于成年人的身心健康也是长期的。研究 建议可以阻止大多数成年人成为烟草使用者，如果他们 可以在青春期保持无烟状态。然而，并不是所有的年轻人都从 吸烟会导致尼古丁依赖(ND)。为了做好预防工作 要想让吸烟最有效，重要的是要阐明潜在的 推动ND进展的机制，以及获得更好的 了解脆弱性的个体差异。来自不同领域的数据 一系列研究表明，抑郁症和新城疫之间存在密切联系。 然而，这两种疾病之间联系的潜在机制是 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 同时患有新城疫和抑郁症。采用纵向设计， 这项调查旨在检查 下丘脑-垂体-肾上腺(HPA)调节失调与吸烟风险 四组青少年新城疫的发生和发展：(1)抑郁 不吸烟的青少年；(2)抑郁的青少年 (3)无吸烟史或无吸烟史的正常青少年 烟草使用情况；以及(4)目前有烟草使用情况的正常青少年。试点数据 来自我们实验室的研究表明，睡前皮质醇升高会增加 非尼古丁物质相关疾病和复发的风险 抑郁青少年中的抑郁发作。其他数据表明， 抗抑郁剂(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 AD药物对HPA轴的下调作用。如果我们的初步结果， 显示高皮质醇与药物使用风险之间的关系 精神障碍，延伸到ND，这一发现可能对 确定患有这些疾病的青年亚群谁可能受益最大 来自AD或抗糖皮质激素治疗的策略。这将是非常重要的 临床意义因为，作为一个群体，年轻人往往表现出更多 与成年抑郁症患者相比，AD反应的变异性。更有针对性 在病程早期采取有效的干预措施可能是 有助于降低与新城疫相关的长期发病率和死亡率。 即使只有一小部分有新城疫风险的青少年可以通过 这样的手段，因为有很多直接的以及间接的负面影响 与新城疫相关的后果，这将对公众健康产生重大影响 重要性。

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.