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

这个K23奖项的目标是发展申请人成为一个独立的调查员与先进的 多模式神经影像学和临床研究方法的技能，以支持他的职业目标，建立一个 一系列研究将奖励脑回路作为物质使用的共同病因脆弱性 精神障碍和主要情绪障碍并存。有了这个奖项，申请人将调查结构 同时发生酒精使用障碍（AUD）和双相情感障碍时奖励脑回路的功能 (AUD+BD），这在很大程度上仍然是未知的，以支持更精确的神经生物学靶点的发展 治疗AUD+BD。拟议的职业发展和培训计划直接与他的 在儿童/家庭临床心理学，社会奖励和决策，利用高风险 设计和正在进行的成人AUD（+/-BD）神经影像学研究。在这个著名的导师的支持下， 团队，申请人将：1）获得先进的知识和熟练的功能磁共振成像 （fMRI），扩散峰度成像（DKI），并与这些数据的复杂分析; 2）开发一个深层次的 了解从青春期到成年期的AUD和BD的神经生物学; 3）非常擅长 进行与家庭有关的酒精和BD临床研究;和4）改善他的granuloma顺利 向独立研究过渡。这些目标将通过功能磁共振成像的严格实践培训来实现 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; 与家庭进行神经影像学研究;并成功完成各种校内 盛大的培训。拟议的多模态神经成像研究的目的是定义奖励 患有AUD+BD的父母及其未受影响的青少年的脑回路结构和功能 对照仅由亲本AUD定义的二分体（每组n=25）。这项研究直接与 通过两个最重要的NIAAA倡议，重点是增加对AUD神经生物学的理解， 跨年龄组共同发生的精神病理学背景。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配对测量白色人的脑功能 物质（WM）通路微结构。中心假设是：1）成年人和他们的未受影响的 相对于单独的AUD，AUD+BD的后代（二分体）将表现出对奖励的过度激活（具有扰动）。 功能连接性），以及2）WM微观结构完整性将在多组 AUD+BD二元组相对于AUD二元组。K23研究的结果将产生重要的初步数据， 对于纵向R 01，确定了目前接受治疗的AUD+BD患者的奖励相关内表型。 现有的临床治疗方法不足。申请人将获得专家的支持和指导 在过去的10多年里，导师们成功地进行了AUD+BD研究。

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.