Neural Substrates of Cigarette Craving, Withdrawal, and Relief: Male-Female Differences

香烟渴望、戒断和缓解的神经基础：男女差异

• 批准号: 10534070
• 负责人: Edythe Danick London
• 金额: $ 12.51万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10534070
• 关键词: Abstinence; Address; Advanced Development; Affect; Anterior; Anxiety; Anxiety Disorders; Attenuated; Award; Big Data; Brain; Cigarette; Cues; Data; Development; Disease; Dorsal; Evaluation; Exhibits; Failure; Female; Functional Magnetic Resonance Imaging; Glutamates; Health; Heart Diseases; Individual; Intervention; Ketamine; Link; Luteal Phase; Machine Learning; Magnetic Resonance Spectroscopy; Malignant neoplasm of cervix uteri; Measures; Menstrual cycle; Mood Disorders; Negative Reinforcements; Nicotine Dependence; Ovarian hormone; Parents; Participant; Patient Self-Report; Persons; Positioning Attribute; Prevalence; Reporting; Request for Proposals; Research; Rest; Sample Size; Sampling; Sex Differences; Smoke; Smoker; Smoking; Smoking Behavior; Smoking Cessation Intervention; Substance Use Disorder; Testing; Thinking; Tobacco Use Disorder; Training; Withdrawal; Withdrawal Symptom; Woman; Work; biobank; cigarette craving; cigarette smoke; cingulate cortex; craving; depressive symptoms; drug craving; drug relapse; experience; glutamatergic signaling; indexing; male; men; negative affect; neural network; neurotransmission; non-smoker; parent grant; parent project; preventable death; programs; proliferative phase Menstrual cycle; psychologic; relapse prediction; relating to nervous system; rumination; sex; smoking abstinence; smoking cessation; stress reactivity; success; support vector machine

PROJECT SUMMARY (Parent Award) Smoking is the leading cause of preventable death and disease in the U.S., and women disproportionately suffer some health consequences of smoking, such as heart disease and cervical cancer. Compared to men, women experience stronger withdrawal symptoms and have more difficulty maintaining long-term abstinence from smoking, and smoking-cessation treatments are not equally helpful to men and women. The underlying differences in brain function that drive these male-female differences remain unknown, and understanding them can guide development of personalized smoking-cessation therapies. Glutamatergic neurotransmission is a promising target for smoking cessation therapy, but male-female differences that can impact the efficacy of glutamatergic treatments have not been investigated. Reducing glutamate levels within the Salience Network, especially in the dorsal anterior cingulate cortex (dACC) may facilitate smoking cessation. Smokers have higher glutamate (Glu) in the dACC than nonsmokers and exhibit a positive correlation of dACC Glu with reactivity within the default-mode network to smoking-related cues. Given these findings and sex differences in brain glutamate levels in healthy individuals, it is important to test for male- female differences in the influence of dACC Glu on craving and negative states during withdrawal and their relief after smoking, as well as the neural substrates that underlie these states. We will combine self-report measures with magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) to address three specific aims: Aim 1. Determine male-female differences in the association of Glu signal in the dACC with cigarette craving and negative states during abstinence (negative affect, psychological withdrawal, and anxiety). Aim 2. Determine male-female differences in the association of Glu in the dACC with smoking-induced relief of craving and negative states (i.e., negative reinforcement); and Aim 3. Determine male-female differences in the association of Glu in the dACC with resting- state functional connectivity (rsFC) within and between large-scale neural networks. The aims of this project focus on pre-smoking assessments of Glu in the dACC and rsFC of neural networks; however, pre- and post- smoking assessments (self-report, fMRI, and MRS) will be completed in 60 smokers (30 men and 30 women) after overnight (~12h) abstinence. Women will complete these assessments on 2 separate days, during the follicular and luteal phases, to allow evaluation of menstrual-cycle and ovarian hormone effects. The findings can help advance development of personalized, sex-specific smoking cessation therapies.

项目概要 （家长奖） 吸烟是美国可预防的死亡和疾病的主要原因，而女性遭受的影响尤为严重 吸烟对健康造成一些影响，例如心脏病和宫颈癌。与男性相比，女性 经历更强烈的戒断症状并且更难以维持长期戒断 吸烟和戒烟治疗对男性和女性的帮助并不相同。底层的 导致这些男女差异的大脑功能差异仍然未知，并且了解它们 可以指导个性化戒烟疗法的开发。 谷氨酸能神经传递是戒烟治疗的一个有希望的目标，但男性和女性 尚未研究可能影响谷氨酸治疗功效的差异。减少 显着网络内的谷氨酸水平，尤其是背侧前扣带皮层 (dACC) 中的谷氨酸水平可能 促进戒烟。吸烟者 dACC 中的谷氨酸 (Glu) 含量高于不吸烟者，并且表现出 dACC Glu 与默认模式网络内对吸烟相关线索的反应性呈正相关。给定 这些发现以及健康个体大脑谷氨酸水平的性别差异，测试男性非常重要 dACC Glu 对戒断期间的渴望和消极状态及其缓解的影响的女性差异 吸烟后，以及这些状态下的神经基质。 我们将自我报告措施与磁共振波谱 (MRS) 和功能相结合 磁共振成像 (fMRI) 旨在解决三个具体目标： 目标 1. 确定男女差异 dACC 中的 Glu 信号与香烟渴望和戒烟期间的负面状态之间的关联 （负面情绪、心理退缩和焦虑）。目标 2. 确定男性和女性在 dACC 中的 Glu 与吸烟引起的烟瘾缓解和消极状态（即消极状态）之间的关联 加强）;目标 3. 确定 dACC 中 Glu 与静息相关性的男女差异 大规模神经网络内部和之间的状态功能连接（rsFC）。该项目的目标 重点关注神经网络 dACC 和 rsFC 中 Glu 的吸烟前评估；然而，前和后 将对 60 名吸烟者（30 名男性和 30 名女性）完成吸烟评估（自我报告、功能磁共振成像和 MRS） 隔夜（约 12 小时）禁欲后。女性将在不同的两天内完成这些评估 卵泡期和黄体期，以评估月经周期和卵巢激素的影响。研究结果 可以帮助推进个性化、针对特定性别的戒烟疗法的开发。