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奖项的目标是将申请者发展成为一名具有高级技能的独立调查员 多模式神经成像和临床研究方法技能支持他的职业目标，即建立一个 一系列研究将奖赏脑回路作为物质使用的共同病因学易损性进行调查 精神障碍和主要情绪障碍并存。有了这个奖项，申请者将研究结构 在酒精使用障碍(AUD)和双相情感障碍中奖赏脑回路的功能 (AUD+BD)，这在很大程度上仍不为人所知，以支持开发更精确的神经生物学靶点 治疗AUD+BD。拟议的职业发展和培训计划直接与他的 有儿童/家庭临床心理、社会奖励和决策经验，有利用高风险的经验 设计和正在进行的成人AUD(+/-BD)神经成像研究。在这一著名导师的支持下 团队，申请者将：1)在功能磁共振成像方面获得高级知识和熟练程度 (FMRI)，扩散峰度成像(DKI)，以及对这些数据的复杂分析；2)开发深层次的 从青春期到成年期对AUD和BD的神经生物学的了解；3)非常熟练地 进行与家庭相关的酒精和BD临床研究；4)提高他的勇气，使 向研究独立过渡。这些目标将通过严格的fmri实践培训来实现。 和DKI；在专家咨询支持下成功完成神经成像统计课程； 有关AUD和BD神经生物学、评估和治疗的指导性阅读系列； 与家庭一起进行神经成像研究；并成功完成各种校园活动 施展手腕训练。拟议的多模式神经成像研究的目标是定义奖励 AUD+BD父母及其正常青少年的脑回路结构和功能 子代(DUAD)对抗亲代AUD单独定义的DUD(每组25例)。这项研究直接与 NIAAA的两项最重要的倡议是通过重点增加对AUD神经生物学的了解 不同年龄段共同发生的精神病理学的背景。拟议的目标将衡量奖励电路 使用社会奖励和决策的脑功能核磁共振任务与DKI配对测量白色 物质(WM)途径微观结构。中心假设是：1)成虫和其未受影响的成虫 与单独的AUD相比，AUD+BD的后代(二联体)将表现出对奖励的过度激活(带有干扰 功能连接性)，以及2)WM微结构完整性将在以下几组中降低 AUD+BD双联相对于AUD双联。这项K23研究的结果将产生重要的初步数据 对于纵向R01，为AUD+BD患者建立奖励相关内表型，这些患者目前 现有的临床治疗效果不佳。申请者将得到专家的支持和指导 导师在过去10多年中成功地进行了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.