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: 10215729
• 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/10215729
• 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; multimodality; 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奖项的目标是将申请人培养成为具有先进水平的独立研究者 多模式神经影像和临床研究方法技能支持他建立一个职业目标 研究奖励大脑回路作为物质使用的共同病因脆弱性的研究系列 障碍和主要情绪障碍同时发生。有了这个奖项，申请人将研究结构 奖励脑回路在同时发生的酒精使用障碍（AUD）和双相情感障碍中的功能 （AUD+BD）对于支持更精确的神经生物学目标的开发仍然知之甚少 用于治疗AUD+BD。拟议的职业发展和培训计划与他的直接相关 具有儿童/家庭临床心理学、社会奖励和决策、高风险利用方面的经验 设计以及正在进行的成人 AUD(+/-BD) 神经影像研究。在这位著名导师的支持下 团队中，申请人将：1）获得功能磁共振成像的先进知识和熟练程度 (fMRI)、扩散峰度成像 (DKI) 以及对这些数据的复杂分析； 2）深入发展 了解从青春期到成年的 AUD 和 BD 的神经生物学； 3）变得非常擅长 开展与家庭相关的酒精和双相情感障碍临床研究； 4）提高他的资助技巧，以实现顺利的 向研究独立的过渡。这些目标将通过严格的功能磁共振成像实践培训来实现 和 DKI；在专家咨询支持下成功完成神经影像统计学课程； AUD 和 BD 神经生物学、评估和治疗的指导阅读系列；强化辅导 与家人一起进行神经影像研究；以及各项校内活动的顺利完成 资助培训。拟议的多模式神经影像研究的目标是定义奖励 患有 AUD+BD 的父母及其未受影响的青少年的大脑回路结构和功能 后代（二元组）与仅由父母 AUD 定义的二元组（每组 n=25）。这项研究直接对齐 通过两项最重要的 NIAAA 举措，重点关注增加对 AUD 神经生物学的了解 跨年龄组同时发生的精神病理学背景。拟议的目标将测量奖励电路 使用社会奖励和决策 fMRI 任务结合 DKI 测量白种人的大脑功能 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群体 相对于单独的 AUD，具有 AUD+BD 的后代（二元体）将表现出对奖励的过度激活（受到干扰 功能连接）由于 BD 共现，以及 2）WM 微观结构完整性将在一组中降低 AUD+BD 二元组相对于 AUD 二元组。这项 K23 研究的结果将产生重要的初步数据 纵向 R01 为目前正在接受治疗的 AUD+BD 患者建立奖励相关的内表型 现有的临床治疗手段不足。申请人将得到专家的支持和指导 导师在过去 10 多年里成功进行了 AUD+BD 研究。