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)与烟草使用风险的增加和 其他物质使用障碍。特别是，拥有更多A的个体更多 可能吸烟，在较小的年龄开始吸烟，进展到吸烟更重，有 依赖程度越高，戒烟的可能性就越小。然而，很少有人体实验室 已经进行了研究，以检查ACE和吸烟风险之间的相互作用，以及 人们对这些关联背后的机制知之甚少。基于几个 结合证据，我们提出了一个翻译框架，在这个框架中，ACE 与皮质纹状体回路改变有关，导致奖赏失调 处理，这反过来又增加了对滥用药物的强化影响的敏感性，包括 尼古丁。这项拟议的研究将应用实验室模型对最初的尼古丁暴露进行研究， 鼻腔喷雾剂检查青少年尼古丁的主观反应和增强效果 成年非吸烟者(n=150)，Ace病史从0到4或更多。参与者将 首先完成一项旨在评估中脑边缘反应性的功能性神经成像方案 金钱奖励、前额叶抑制控制和皮质纹状体功能连接。 对0、0.5或1毫克尼古丁喷雾剂的主观反应将在 三次单独的固定剂量检查。然后，我们将评估尼古丁在 选择会议。一般来说，我们假设增加对ACE的暴露将与 尼古丁的积极主观和强化作用更大，皮质纹状体的这种缺陷 电路将调节ACE和尼古丁反应之间的联系，而这 女性之间的关联性将会更强。这些结果将提供一个关键的翻译 展示早期生活应激对神经生物学通路影响的动物模型 与上瘾有关。此外，这项工作将有助于解释吸烟风险增加的原因。 在接触ACEs的个人中，并将对预防和治疗 在这个高危人群和更远的地方吸烟。