Psychobiological Mechanisms of Stress & Smoking Relapse

描述（由申请人提供）：烟草成瘾是癌症和心血管疾病的主要可预防原因。尽管在过去20年里，人们加快了制定有效戒烟策略的努力，但长期成功率令人失望。大多数吸烟者在尝试戒烟后的两周内复吸。压力是最常见的吸烟复发诱因之一。应激诱发复发的机制尚不清楚。如果没有对吸烟者压力相关的心理生理变化的具体了解，减少吸烟复发的针对性努力将仍然有限。我们研究的长期目标是确定导致吸烟复发的心理生物学机制。该项目的具体目标是确定早期戒烟期间和急性应激反应中垂体肾上腺皮质活动的变化在多大程度上预测吸烟者试图戒烟的复发。我们的中心假设是，在早期戒断期间，通过动态监测和应激反应来测量促肾上腺皮质激素（ACTH）和皮质醇的变化，可以预测复发的时间。这一假设是基于我们之前的研究和观察到的心理社会压力因素会增加吸烟复发的风险。这项拟议的研究将包括在24小时内动态测量皮质醇的昼夜水平和皮质醇的觉醒上升，而参与者仍以正常的吸烟率（基线）吸烟，以及在24-48小时的戒烟期间。该研究还将包括测量血浆ACTH、皮质醇、血压和两次实验室压力测试期间（随意吸烟期间和戒烟48小时后）的戒断症状。在每个课程中，参与者将进行三个有压力的挑战（公开演讲，数学和冷压力）。这项研究的重点是下丘脑-垂体-肾上腺皮质轴，一个重要的生物系统，最近涉及成瘾。该研究综合了激素、血液动力学和心理指标，以确定吸烟者在戒烟尝试的关键时期的压力反应模式，并利用这些信息以前瞻性的方式确定12个月期间复发的特定生物行为标记。这项研究的一个重要目标是确定男性和女性在心理生物学变化方面的差异，并确定这些差异在多大程度上预测复发。研究结果将对制定对戒烟感兴趣和复发风险高的吸烟者的最佳诊断和干预策略具有重要意义。降低复发率将大大有助于减少烟草使用及其破坏性影响。

DESCRIPTION (provided by applicant): Tobacco addiction is the leading preventable cause of cancer and cardiovascular diseases. Although the last two decades have witnessed accelerated efforts to develop effective smoking cessation strategies, the long-term success rates have been disappointing. The majority of smokers relapse within two weeks of a cessation attempt. Stress is one of the most commonly reported precipitants of smoking relapse. Mechanisms responsible for the stress-precipitated relapse are not known. Without specific knowledge of the stress-related psychobiological changes in smokers, targeted efforts to reduce smoking relapse will remain limited. The long-term goal of our research is to determine the psychobiological mechanisms responsible for smoking relapse. The specific goal of this project is to determine the extent to which changes in the pituitaryadrenocortical activity during early abstinence and in response to acute stress predict relapse in smokers attempting to quit. Our central hypothesis is that exaggerated adrenocorticotropic hormone (ACTH) and cortisol changes during early abstinence, as measured during ambulatory monitoring and in response to stress, predict time to relapse. This hypothesis is based on our previous studies and on the observation that psychosocial stressors increase the risk for smoking relapse. The proposed study will include ambulatory measurement of diurnal cortisol levels and awakening rise in cortisol during 24 hours while participants are still smoking at their normal rates (baseline), and during the period of 24-48 hours of abstinence. The study will also include measurement of plasma ACTH, cortisol, blood pressure, and withdrawal symptoms during two laboratory stress sessions (during ad libitum smoking and after 48 hours of abstinence). During each session participants will perform three stressful challenges (public speaking, math, and cold pressor). This research focuses on the hypothalamic-pituitary-adrenocortical axis, an important biological system recently implicated in addiction. The research integrates hormonal, hemodynamic, and psychological indices to determine stress response patterning among smokers during this critical period of a quit attempt, and uses this information in a prospective fashion to identify specific biobehavioral markers of relapse over a 12-month period. An important goal for this research is to determine differences in psychobiological changes between men and women, and establish the extent to which these differences predict relapse. The results will be important in the development of optimal diagnostic and intervention strategies for smokers interested in cessation and at high risk for relapse. Reducing relapse rates will contribute significantly towards decreasing tobacco use and its devastating effects.