Neurobehavioral mechanisms linking childhood adversity to increased risk for smoking

将童年不幸与吸烟风险增加联系起来的神经行为机制

• 批准号: 10670365
• 负责人: Maggie M Sweitzer
• 金额: $ 56.47万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670365
• 关键词: 21 year old; Accounting; Adolescent; Adult; Age; Animal Model; Behavioral; Behavioral Mechanisms; Behavioral Paradigm; Brain; Cigarette; Corpus striatum structure; Dependence; Dopamine; Dose; Exposure to; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Household; Human; Individual; Individual Differences; Intranasal Administration; Laboratories; Laboratory Study; Lead; Link; Literature; Measures; Mediating; Methods; Modeling; Neurobiology; Nicotine; Nicotine Nasal Spray; Nose; Outcome; Participant; Pathway interactions; Physiological; Placebos; Prevention; Procedures; Process; Protocols documentation; Psychological reinforcement; Reaction; Recording of previous events; Research; Rewards; Risk; Role; Severities; Sex Differences; Smoker; Smoking; Smoking treatment; Socioeconomic Status; Stress; Substance Use Disorder; Testing; Time; Tobacco use; Translations; Visit; Woman; Work; addiction; adverse childhood events; childhood adversity; cigarette smoke; cognitive control; depressive symptoms; design; drug of abuse; early life adversity; early life stress; experience; high risk population; insight; men; neglect; neurobehavioral; neuroimaging; neuromechanism; nicotine exposure; nicotine use; non-smoker; non-smoking; preference; prospective; response; reward anticipation; reward processing; sex; smoking exposure; smoking initiation; translational framework; young adult

Adverse childhood experiences (ACEs) have been linked to increased risk of tobacco use and other substance use disorders. In particular, individuals with a higher number of ACEs are more likely to smoke cigarettes, initiate smoking at earlier ages, progress to heavier smoking, have higher levels of dependence, and are less likely to quit. However, very few human laboratory studies have been conducted to examine interactions between ACEs and risk for smoking, and the mechanisms underlying these associations are poorly understood. Based on several converging lines of evidence, we propose a translational framework in which ACEs are associated with alterations in corticostriatal circuitry contributing to dysregulated reward processing, which in turn increases sensitivity to reinforcing effects of drugs of abuse, including nicotine. The proposed research will apply a laboratory model of initial nicotine exposure using nasal spray to examine subjective reactions and reinforcing effects of nicotine among young adult non-smokers (n=150) with a history of ACEs ranging from 0 to 4 or more. Participants will first complete a functional neuroimaging protocol designed to assess mesolimbic reactivity to monetary reward, prefrontal inhibitory control, and corticostriatal functional connectivity. Subjective reactions to 0, .5, or 1 mg doses of nicotine nasal spray will be assessed during three separate fixed-dose visits. We will then evaluate reinforcing effects of nicotine during a choice session. In general, we hypothesize that increased exposure to ACEs will be associated with greater positive subjective and reinforcing effects of nicotine, that deficits in corticostriatal circuitry will mediate the association between ACEs and nicotine reactions, and that this association will be stronger among women. These results will provide a critical translation from animal models demonstrating consequences of early life stress on neurobiological pathways relevant to addiction. Moreover, this work will help to explain the increased risk for smoking among individuals exposed to ACEs and will have implications for prevention and treatment of smoking in this high-risk population and beyond.

不良童年经历（ACE）与烟草使用风险增加有关， 其他物质使用障碍。特别是，ACE数量较多的个体 可能吸烟，在较早的年龄开始吸烟，吸烟量增加， 更高的依赖性，更不可能戒烟。然而，很少有人类实验室 已经进行了研究来检查ACE和吸烟风险之间的相互作用， 对这些关联的机制知之甚少。基于几 收敛线的证据，我们提出了一个翻译框架，ACE是 与皮质纹状体回路的改变有关，导致奖赏失调 加工，这反过来又增加了对滥用药物的强化作用的敏感性，包括 尼古丁。这项拟议的研究将采用一种实验室模型， 青少年对尼古丁的主观反应及增强作用 成人非吸烟者（n=150），ACE病史范围为0 - 4或更多。参与者将 首先完成一个功能性神经成像协议，旨在评估中脑边缘反应， 金钱奖励、前额叶抑制控制和皮质纹状体功能连接。 将在治疗期间评估对0、.5或1 mg剂量尼古丁鼻喷雾剂的主观反应。 三次单独的固定剂量访视。然后，我们将评估尼古丁的强化作用， 选择会议。总的来说，我们假设ACE暴露的增加与 随着尼古丁的积极主观和强化作用的增加，皮质纹状体 电路将介导ACE和尼古丁反应之间的关联，这 女性之间的联系会更强。这些结果将提供一个关键的翻译， 动物模型证明早期生活压力对神经生物学通路的影响 与成瘾有关。此外，这项工作将有助于解释吸烟的风险增加， 在暴露于ACE的个体中，将对预防和治疗 吸烟在这一高风险人群和超越。