YALE-SCORE ON SEX DIFFERENCES IN ALCOHOL USE DISORDER

耶鲁大学酒精使用障碍性别差异评分

• 批准号: 10599817
• 负责人: SHERRY ANN MCKEE
• 金额: $ 167.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-10 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599817
• 关键词: Accounting; Address; Affect; Alcohol consumption; Alcohols; Area; Award; Basic Science; Behavioral; Biological; Biology; Biomedical Research; Brain; Cardiovascular Diseases; Centers of Research Excellence; Clinical Sciences; Cognitive deficits; Collaborations; Communities; Consultations; Darkness; Data; Development; Ensure; Environment; Ethanol Metabolism; FDA approved; Faculty; Funding; Goals; Gonadal Steroid Hormones; Health; Healthcare; Infrastructure; Institution; Laboratories; Leadership; Malignant Neoplasms; Mentors; Modeling; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Negative Reinforcements; Neurobiology; Neuroimmune; Neurosciences; Pharmaceutical Preparations; Policies; Positive Reinforcements; Positron-Emission Tomography; Psychiatry; Public Health; Publications; Research; Research Personnel; Research Priority; Resources; Rewards; Risk; Role; Sampling; Sex Differences; Side; Specialized Center; Stress; Structure; Substance abuse problem; System; Teacher Professional Development; Therapeutic; Translating; Translational Research; Translations; United States; Withdrawal; Woman; Women' s Health; addiction; alcohol abuse therapy; alcohol use disorder; behavioral pharmacology; cerebral atrophy; drinking; economic cost; experience; faculty support; heuristics; hypothalamic-pituitary-adrenal axis; improved; interest; liver inflammation; men; metabolomics; mortality; negative affect; neuroadaptation; neurochemistry; neurotoxicity; next generation; novel therapeutics; outreach; outreach program; programs; recruit; response; sex; success; therapeutic target; translational approach; translational pipeline; translational scientist

Our proposed Yale-Specialized Center of Research Excellence (SCORE) on sex differences in alcohol use disorder (AUD) brings together a team of leading basic and clinical science experts to pursue an interdisciplinary, translational, cross-species program of research aimed at identifying novel therapeutics to address the recent surge in rates of AUD in women. Over the past 10 years, rates of AUD in women have increased by 84%, translating to 10.5 million women across the United States. Alcohol use is the third leading cause of preventable morbidity and mortality in the United States and women drinkers experience exacerbated health risks associated with alcohol consumption when compared to men. FDA-approved medications for AUD have relatively low efficacy, all were developed with samples of men, and none target factors that differentially maintain drinking in women. A considerable body of data identifies that women are more likely to drink to regulate negative affect and stress, while men are more likely to drink for alcohol-related positive reinforcement. Koob & Volkow194 have developed a heuristic framework of the addiction cycle, where the ‘withdrawal/negative affect stage’ involves drinking motivated by stress and other negative affect states, also termed ‘the dark side of addiction’. Neuroadaptations during this stage identify reward deficits and stress surfeits, which drive compulsive drinking. Using this negative reinforcement model to guide our research, we plan to target key brain structures, neurochemical systems, HPA-axis activity, neuroimmune function, alcohol metabolism, and sex steroid hormones, which are hypothesized to differentially motivate alcohol consumption in women. To date, there has not been a concerted effort to incorporate sex as a biological variable (SABV) into AUD medication development. Consequently, the focus of our Yale-SCORE represents a high research priority topic for both NIAAA and ORWH. We propose three Projects that will have inter-related and shared goals, with each providing unique contributions to inform and expedite the development of AUD therapeutics for women with AUD. The Projects will be supported by three Cores and an institutional environment with exceptional resources and infrastructure to support translational science. Our specific aims and objectives of the Yale-SCORE are to: AIM 1: Use a neurobiologically-informed approach focusing on the ‘dark side of addiction’ to inform and expedite the development of sex-appropriate therapeutics targeting stress and negative affect, which differentially maintain drinking in women. AIM 2: Mentor SCORE-Early Investigators to become the next generation of biomedical and behavioral researchers focused on alcohol and women’s health spanning the T1 to T4 translational spectrum. AIM 3: Be an institutional, regional, and national resource galvanizing the study of sex differences in relation to alcohol use across T1 to T4 translation by providing expert consultation, supporting faculty training awards, leveraging national data on sex and alcohol use to inform treatment and policy, and providing a program of outreach and dissemination.

我们建议耶鲁大学专门研究卓越中心（SCORE）研究酒精使用的性别差异