An investigation of reward brain circuitry structure and function in individuals with co-occurring alcohol use disorder and bipolar disorder and their unaffected offspring

对同时患有酒精使用障碍和双相情感障碍的个体及其未受影响的后代的奖励脑回路结构和功能的研究

• 批准号: 10491069
• 负责人: William Mellick
• 金额: $ 20.82万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491069
• 关键词: Adolescence; Adult; Affect; Alcohols; Amygdaloid structure; Anterior; Award; Base of the Brain; Biological Markers; Bipolar Disorder; Brain; Child; Clinical; Clinical Psychology; Clinical Research; Clinical Treatment; Consultations; Data; Decision Making; Development; Development Plans; Diffusion; Etiology; Exhibits; Family; Functional Magnetic Resonance Imaging; Future; Goals; Heritability; Image; Imaging Techniques; Individual; Internal Capsule; Investigation; Knowledge; Limb structure; MRI Scans; Measurement; Measures; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Mood Disorders; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Parents; Pathway interactions; Patient Self-Report; Patients; Population; Prefrontal Cortex; Psychopathology; Radiation; Reading; Research; Research Design; Research Methodology; Research Personnel; Rewards; Series; Structure; Substance Use Disorder; Testing; Training; Ventral Striatum; adolescent offspring; age group; alcohol use disorder; brain circuitry; brain dysfunction; brain reward regions; career; career development; clinical application; cognitive control; design; developmental neurobiology; endophenotype; experience; high risk; improved; interest; multimodal neuroimaging; neuroimaging; offspring; preventive intervention; research and development; reward circuitry; skills; social; statistics; suicidal risk; treatment response; trend; white matter

The goal of this K23 award is to develop the applicant into an independent investigator with advanced multimodal neuroimaging and clinical research methods skills to support his career objective of establishing a line of research investigating reward brain circuitry as a shared etiological vulnerability to substance use disorder and major mood disorder co-occurrence. With this award, the applicant will investigate the structure and function of reward brain circuitry in co-occurring alcohol use disorder (AUD) and bipolar disorder (AUD+BD) which remains largely unknown to support the development of more precise neurobiological targets for the treatment of AUD+BD. The proposed career development and training plan is directly aligned with his prior experience in child/family clinical psychology, social reward and decision-making, utilization of high-risk designs, and ongoing adult AUD(+/-BD) neuroimaging research. With the support of this renowned mentorship team, the applicant will: 1) gain advanced knowledge and proficiency in functional magnetic resonance imaging (fMRI), diffusion kurtosis imaging (DKI), and sophisticated analyses with these data; 2) develop a deep understanding of the neurobiology of AUD and BD from adolescence into adulthood; 3) become highly adept at conducting family-related alcohol and BD clinical research; and 4) improve his grantsmanship for a smooth transition to research independence. These goals will be achieved through rigorous hands-on training in fMRI and DKI; the successful completion of neuroimaging statistics coursework with expert consultation support; guided reading series on AUD and BD neurobiology, assessment, and treatment; intensive mentorship in conducting neuroimaging research with families; and the successful completion of various on-campus grantsmanship trainings. The objective of the proposed multimodal neuroimaging study is to define reward brain circuitry structure and function among sets of parents with AUD+BD and their unaffected adolescent offspring (dyads) against dyads defined by parental AUD alone (n=25 per group). This study is directly aligned with two foremost NIAAA initiatives through focus on increasing understanding of AUD neurobiology in the context of co-occurring psychopathology across age groups. The proposed aims will measure reward circuitry brain function using social reward and decision-making fMRI tasks paired with DKI for measurement of white matter (WM) pathway microstructure. The central hypotheses are: 1) sets of adults and their unaffected offspring (dyads) with AUD+BD relative to AUD alone will exhibit hyperactivation to reward (with perturbed functional connectivity) due to BD co-occurrence, and 2) WM microstructural integrity will be reduced in sets of AUD+BD dyads relative to AUD dyads. The results of this K23 study will generate important preliminary data for a longitudinal R01 establishing reward-related endophenotypes for AUD+BD patients who are currently underserved by existing clinical treatments. The applicant will receive support and guidance from expert mentors successfully conducting AUD+BD studies for the past 10+ years.

该K23奖的目标是将申请人培养成高级的独立调查员 多模式的神经影像学和临床研究方法技能，以支持他的职业生涯目标 研究奖励脑电路的研究线作为对药物使用的共同病因脆弱性 障碍和重大情绪障碍同时出现。有了该奖项，申请人将调查结构 奖励脑电路在同时发生的酒精使用障碍（AUD）和躁郁症中的功能 （aud+bd），这在很大程度上尚不清楚，以支持开发更精确的神经生物学目标 用于处理aud+bd。拟议的职业发展和培训计划与他的 在儿童/家庭临床心理学，社会奖励和决策，高风险利用方面的先前经验 设计和正在进行的成人AUD（+/- BD）神经影像学研究。在这个著名的指导的支持下 团队，申请人将：1）获得功能磁共振成像的高级知识和熟练程度 （fMRI），扩散峰度成像（DKI）和这些数据进行了复杂的分析； 2）深入 了解从青春期到成年的AUD和BD神经生物学； 3）高度熟练 进行与家庭有关的酒精和BD临床研究； 4）提高他的赠款技巧，以平稳 过渡到研究独立性。这些目标将通过fMRI进行严格的动手培训来实现 和dki;通过专家咨询支持，成功完成神经影像学统计课程； 关于AUD和BD神经生物学，评估和治疗的指导阅读系列；密集的指导 与家庭进行神经影像学研究；以及成功完成各种校园 授予技巧培训。拟议的多模式神经影像学研究的目的是定义奖励 AUD+BD的父母及其未受影响的青少年的脑电路结构和功能 对后代（二元组）针对由父母AUD定义的二元组（每组n = 25）。这项研究直接对齐 通过将注意力集中在增加对AUD神经生物学中的两项NIAAA倡议中 跨年龄段共同出现的心理病理学的背景。拟议的目标将衡量奖励电路 使用社会奖励和决策FMRI任务与DKI配对以测量白色的大脑功能 物质（WM）途径微观结构。中心假设是：1）成年人及其未受影响的集合 具有AUD+BD相对于单独使用AUD的后代（二元组）将表现出过度激活以奖励 功能连接性）由于BD共发生，2）WM微结构完整性将降低 AUD+BD相对于AUD DYADS。这项K23研究的结果将产生重要的初步数据 对于纵向R01，为目前为AUD+BD患者建立与奖励相关的内表型 现有临床治疗的服务不足。申请人将获得专家的支持和指导 在过去的10年中，导师成功地进行了AUD+ BD研究。