Multimodal Neuroimaging of Alcohol Cues, Cortisol Response and Compulsive Motivation

酒精暗示、皮质醇反应和强迫动机的多模式神经影像

• 批准号: 10221458
• 负责人: Sara Keelan Blaine
• 金额: $ 24.1万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221458
• 关键词: Acute; Adult; Age; Alcohol consumption; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Animal Model; Area; Award; Beer; Behavior; Behavioral; Blood; Brain; Chronic; Clinical; Clinical Research; Corpus striatum structure; CpG Islands; Cues; Development; Disease; Drug usage; Educational workshop; Exposure to; FK506 binding protein 5; Foundations; Future; Gender; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Glucocorticoids; Goals; Haplotypes; Health; Heavy Drinking; Human; Hydrocortisone; Imagery; Individual; Infrastructure; Intake; International; Life; Measurement; Mediating; Mentors; Methods; Methylation; Modeling; Motivation; Neurobiology; Neurosciences; Neurosciences Research; Neurosecretory Systems; Oxygen; Pathway interactions; Phase; Physiological; Prefrontal Cortex; Prevention; Relapse; Research; Research Personnel; Research Project Grants; Resources; Risk; Role; Scanning; Scientist; Solid; Stress; Structure; Supervision; Surveys; Taste Perception; Techniques; Testing; Time; Training; Training Programs; Variant; Woman; Work; alcohol abuse therapy; alcohol craving; alcohol cue; alcohol measurement; alcohol relapse; alcohol response; alcohol risk; alcohol use disorder; base; binge drinking; career; career development; cortico-limbic circuits; craving; design; drinking; drinking behavior; experience; follow-up; hazardous drinking; hormonal signals; hypothalamic-pituitary-adrenal axis; longitudinal analysis; meetings; men; multimodality; neural network; neurobiological mechanism; neurochemistry; neuroimaging; neuromechanism; non-smoking; novel; novel therapeutics; preclinical study; preventable death; programs; prospective; recruit; relating to nervous system; response; skills; social; symposium; translational neuroscience

PROJECT SUMMARY The long-term career goal of the applicant is to develop an independent program of research on the neurobiological mechanisms underlying the development of Alcohol Use Disorders (AUDs), specifically those related to binge drinking. Results from the 2014 National Survey on Drug Use and Health show that 26% of adults in the US engaged in binge drinking in the past month (SAMSA 2014). Why some people “mature out” of this behavior while others persist may be due to one’s physiological response to binge drinking. No previous study has assessed whether disrupted cortisol and neural network responses to alcohol cues may drive the compulsive alcohol consumption seen in binge drinking individuals who do not yet have an AUD. Over the course of the applicant’s career, she hopes to contribute to our understanding of the genomic, neuroendocrine, and neural mechanisms that underlie the development of AUDs. So far, she has received excellent training regarding the neurochemical and neuroanatomical substrates (from genetics to functional networks) involved in the effects of acute alcohol on the brain and in the chronic, relapsing course of severe AUDs. On this solid foundation of clinical and behavioral neuroscience, she now aims to obtain further training within the highly productive and supportive infrastructure at Yale in (1) advanced multimodal neuroimaging techniques, (2) the clinical course of hazardous drinking prior to the onset of AUDs, and (3) multilevel, mixed effects longitudinal analyses to launch a career as an independent researcher in the field of interdisciplinary, translational neuroscience research on alcoholism. Without this K99/R00 Pathway to Independence Award, the applicant will not have the protected time, training, or the resources to initiate this new direction of research. This rigorous K99 training program will help the applicant obtain a new skill set required to develop a long-term program of research which incorporates multiple interdisciplinary methods in the study of the development of AUDs. This training plan will be achieved via: 1) structured mentoring programs 2) supervised research experience, 3) formal coursework and seminars/workshops, and 4) attendance at national and international conference meetings. To further the applicant’s training with an independent research project, during the R00 phase, the applicant will recruit beer drinking, non-smoking men and women ages 21-45 (N=90, equal gender) who are either moderate drinkers or binge/heavy drinkers for a single neuroimaging and neuroendocrine assessment to determine if their real world drinking behavior in a prospective one month follow up can be predicted based upon the cortisol and neural network responses to alcohol cues. Finally, the influence of genetic variation in the FK506-binding protein 5 (FKBP5) gene, which regulates cortisol activity, on the cortisol and neural network responses to alcohol cues will be explored. This study will be the basis to build a career in understanding the neurobiological changes that drive risk of AUDs in humans.

项目总结

项目成果

IL-6, but not TNF-α, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers.

• DOI: 10.1016/j.bbih.2023.100645
• 发表时间: 2023-08
• 期刊: Brain, behavior, & immunity - health

People who binge drink show neuroendocrine tolerance to alcohol cues that is associated with immediate and future drinking- results from a randomized clinical experiment.

一项随机临床实验的结果表明，酗酒的人对酒精信号表现出神经内分泌耐受性，这与当前和未来的饮酒有关。

• DOI: 10.1038/s41386-023-01735-9
• 发表时间: 2023
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Blaine,SaraK;Ridner,Clayton;Campbell,Benjamin;Crone,Lily;Macatee,Richard;Ansell,EmilyB;Robinson,JenniferL;Claus,EricD
• 通讯作者: Claus,EricD

DRD2 methylation is associated with executive control network connectivity and severity of alcohol problems among a sample of polysubstance users.

• DOI: 10.1111/adb.12684
• 发表时间: 2020-01
• 期刊: Addiction biology
• 影响因子: 3.4
• 作者: Hagerty SL;YorkWilliams SL;Bidwell LC;Weiland BJ;Sabbineni A;Blaine SK;Bryan AD;Hutchison KE
• 通讯作者: Hutchison KE