Sex Differences in Alcohol Use Disorder Neurodegeneration using Multimodal PET and DTI Neuroimaging

使用多模态 PET 和 DTI 神经影像学研究酒精使用障碍神经变性的性别差异

• 批准号: 10680587
• 负责人: Yasmin Zakiniaeiz
• 金额: $ 17.61万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680587
• 关键词: Abstinence; Address; Age; Alcohol consumption; Alcohols; Archives; Area; Axon; Binding; Biological; Biometry; Brain; Brain imaging; Cerebellum; Clinical; Corpus Callosum; Data; Data Analyses; Data Collection; Data Set; Demyelinations; Diffusion; Disease; Educational workshop; Female; Fiber; Functional disorder; Goals; Growth; Hippocampus; Human; Image; Impairment; Individual; MRI Scans; Magnetic Resonance Imaging; Measures; Memory impairment; Mentored Research Scientist Development Award; Mentors; Microglia; Modeling; Molecular; Multimodal Imaging; Nerve Degeneration; Neurobiology; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurosciences; Outcomes Research; Pattern; Play; Positron-Emission Tomography; Pre-Clinical Model; Prefrontal Cortex; Productivity; Proteins; Publications; Recovery; Research; Research Personnel; Role; Sampling; Scientist; Sex Differences; Short-Term Memory; Smoking; Structure; Supervision; Time; Training; Training Programs; Treatment outcome; United States; Woman; addiction; alcohol abuse therapy; alcohol consequences; alcohol use disorder; axon injury; brain cell; career; cerebral atrophy; collaborative environment; connectome; design; executive function; experience; imaging modality; imaging study; improved; in vivo; innovation; male; medical schools; men; multimodal neuroimaging; multimodality; neuroimaging; neuromechanism; novel; programs; radiotracer; restoration; sex; skills; symposium; theories; white matter

Project Summary/Abstract The program of research and training described in this K01 application will provide the candidate with the requisite skills to become an independent investigator understanding sex differences in neurodegeneration (i.e., microglia and white matter tracts) and neurocognition in alcohol use disorder (AUD) to identify novel treatment targets that address sex differences. The research component of this 5-year plan involves the application of: (1) positron emission tomography (PET) imaging to examine sex differences in neurocognitive function that underlie sex differences in microglia levels in AUD; (2) diffusion tensor magnetic resonance imaging (DTI) to examine sex differences in white matter tract integrity in AUD and; (3) PET and DTI multimodal integration analysis to determine the relationship between microglia levels, white matter tract integrity, and neurocognitive function in women and men with AUD. Sixty (15 male and 15 female) individuals with AUD and 30 age-, sex-, and smoking-matched healthy controls will participate in both PET and DTI scanning to facilitate PET, DTI, and PET/DTI integration analysis. To systematically identify sex differences in patterns of white matter tract integrity, the candidate will also examine data from a large, archived, neuroimaging DTI dataset (The Human Connectome Project), to generate publications and productivity during data collection. This combination of novel data collection and secondary data analyses is designed to maximize the candidate's training via provision of hands-on experience in both: (1) the theory and conduct of her own combined multimodal neuroimaging study under guided supervision of recognized experts; and, (2) the analysis and interpretation of large-scale neuroimaging datasets. In pursuit of these goals, the candidate proposes to undertake further training in four primary areas: (1) the neurobiology of AUD, (2) treatment outcomes research and clinical corelates of AUD, (3) DTI and multimodal neuroimaging, and (4) biostatistical approaches. The opportunities afforded by the K01 mechanism would enable the candidate to embark on a rigorous, structured 5-year program of training and research, designed to provide her with the necessary skills in the four areas highlighted above. This program of study will combine formal didactic courses, directed readings, one-on-one tutorials, specialized workshops, attendance of scientific research conferences, and mentored research experience. The research and training proposed in this K01 provides an ideal interdisciplinary opportunity to achieve the candidate's long-term career goal of becoming an independent scientist with a particular focus on sex as a biological variable in the neurobiology of AUD. The team of mentors and collaborators are leaders in these fields and, together with the stimulating and collaborative environment of the Yale School of Medicine, will facilitate the candidate's growth and prepare her for an independent career at the interface of AUD neuroscience and neuroimaging research.

项目总结/文摘

项目成果

Developing Researchers with Expertise in Sex as a Biological Variable through SCORE Career Enhancement Core Center Programs.

通过 SCORE 职业提升核心中心项目培养具有性别作为生物变量专业知识的研究人员。

• DOI: 10.1089/jwh.2023.0015
• 发表时间: 2023
• 期刊: Journal of women's health (2002)
• 作者: Zakiniaeiz,Yasmin;Peltier,MacKenzieR;Mineur,YannS;Gueorguieva,Ralitza;Picciotto,MarinaR;Petrakis,Ismene;Cosgrove,KellyP;McKee,SherryA
• 通讯作者: McKee,SherryA

Examining the relationship of concurrent obesity and tobacco use disorder on the development of substance use disorders and psychiatric conditions: Findings from the NESARC-III.

检查并发肥胖和烟草使用障碍与物质使用障碍和精神疾病发展的关系：NESARC-III 的发现。

• DOI: 10.1016/j.dadr.2023.100162
• 发表时间: 2023-06
• 期刊: Drug and alcohol dependence reports
• 作者: Fields, L J;Roberts, W;Schwing, I;McCoy, M;Verplaetse, T L;Peltier, M R;Carretta, R F;Zakiniaeiz, Y;Rosenheck, R;McKee, S A
• 通讯作者: McKee, S A

Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.

• DOI: 10.1016/j.bbi.2022.08.016
• 发表时间: 2022-11
• 期刊: Brain, behavior, and immunity

Liquor consumption is associated with other medical conditions in females who consume alcohol.

饮酒女性与其他健康状况有关。

• DOI: 10.1016/j.dadr.2023.100132
• 发表时间: 2023-03
• 期刊: Drug and alcohol dependence reports
• 作者: Verplaetse, Terril L;Roberts, Walter;Peltier, MacKenzie R;Zakiniaeiz, Yasmin;Burke, Catherine;Pittman, Brian;McKee, Sherry A
• 通讯作者: McKee, Sherry A

Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response.

• DOI: 10.1093/ntr/ntac026
• 发表时间: 2022-10-17
• 期刊: NICOTINE & TOBACCO RESEARCH
• 影响因子: 4.7
• 作者: Zakiniaeiz, Yasmin;Liu, Heather;Gao, Hong;Najafzadeh, Soheila;Ropchan, Jim;Nabulsi, Nabeel;Huang, Yiyun;Matuskey, David;Chen, Ming-Kai;Cosgrove, Kelly P.;Morris, Evan D.
• 通讯作者: Morris, Evan D.