Brain Connectivity and Mindfulness Training in Youth with Bipolar Disorder NOS

描述（由申请人提供）：这个面向患者的研究（K24）奖的长期目标是为候选人提供时间和资源，以继续和扩大他在临床研究领域的培训生的指导活动，以创新的方法早期识别和预防儿童情绪障碍。此外，候选人将在先进的MRI方法和基于正念的治疗领域发展自己的事业，以便利用这些知识更好地研究神经网络异常，这些异常会产生早发性双相情感障碍（BD）的风险，以及如何干预可以逆转这些发育异常。候选人将通过相关课程、科学会议、外部咨询、内部合作和指导，以及完成与这些领域相关的拟议研究项目（BD NOS）来实现这一目标。双相情感障碍是一种常见的慢性致残障碍，具有重大的公共卫生负担，通常始于童年或青春期。了解大脑发育如何导致双相障碍的发展将有助于制定有针对性的早期干预和预防措施。鉴于精神药物对发育中的大脑的不良影响尚不清楚，对双相障碍高危人群的非药物干预也应进行探索。正念疗法（MBT）已经成功地用于治疗成人和儿童抑郁症，以及成人双相情感障碍。本应用建议检查双相障碍高危青年的基线静息状态神经网络，以及MBT干预对这些网络和脑形态计量学的影响。首先，我们将研究30名符合BD NOS标准的青少年（13-17岁），严格按照标准化研究标准定义。受试者也将有一级或二级亲属患有双相情感障碍，这构成了一个在四年内发展为双相情感障碍I的高风险群体。我们将使用静息状态功能磁共振成像（rs-fMRI）检查这30名受试者的默认模式网络（DMN），并与20名健康对照（HC）的数据进行比较。我们假设，与HC相比，患有BD NOS的年轻人将改变亚属前扣带（sgACC）功能连通性（FC）： sgACC与DMN的FC较高，sgACC与前扣带背侧和背外侧前额皮质的FC较低。其次，这些受试者将接受为期12周的基于正念的青少年减压（MBSR-T）干预，旨在提高日常正念、冥想技能和对压力源反应的情绪失调的认识。我们假设患有双相障碍的青少年会经历抑郁症状和情绪失调程度的减少，以及功能和正念练习程度的增加。此外，我们预计具有DMN的sgACC的FC会减少，而具有背侧结构的sgACC的FC会增加，左海马体积也会增加。与NIMH战略计划一致，本研究将检查青少年情绪障碍发展的神经生物学风险因素和具有预防潜力的新型干预的神经机制，同时为指导下一代儿科情绪障碍预防领域的临床研究人员创造额外的机会。

DESCRIPTION (provided by applicant): The long-term objective of this Midcareer Investigator Award in Patient-Oriented Research (K24) Award is to provide time and resources to the candidate to continue and expand his mentoring activities of trainees in clinical research careers in the field of innovative methods for early identification and prevention of pediatric mood disorders. Furthermore, the candidate will develop his own career in the areas of advanced MRI methodologies and mindfulness-based therapies in order to use this knowledge to better investigate neural network abnormalities that create risk for early-onset bipolar disorder (BD) and how interventions can reverse these developmental abnormalities. The candidate will reach this goal through relevant coursework, scientific meetings, outside consultation, internal collaboration and mentoring, and completion of a proposed research project relating these fields to youth with BD, not otherwise specified (BD NOS). Bipolar disorder is a common, chronic, and often disabling disorder that carries significant public health burden and commonly begins in childhood or adolescence. Understanding how brain development leads to BD development would aid in developing targeted interventions for early intervention and prevention. Given the unclear adverse effects of psychotropic medications on developing brains, non-pharmacologic interventions in populations at risk for BD should also be explored. Mindfulness based therapies (MBT) have been successfully used to treat adults and children with depression, and adults with bipolar disorder. This application proposes examination of baseline resting state neural networks in youth at high-risk for BD, and the effects of a MBT intervention on these networks and on brain morphometry. First, we will study 30 adolescents (13-17 yo) who meet criteria for BD NOS, strictly defined per standardized research criteria. Subjects will also have a first- or second-degree relative with BD, creating a group at very high risk of progressing to bipolar I disorder within four years. We will use resting state-fMRI (rs-fMRI) to examine default mode networks (DMN) in these 30 subjects and compare with already acquired data from 20 healthy controls (HC). We hypothesize that youth with BD NOS will have altered subgenual anterior cingulate (sgACC) functional connectivity (FC) compared with HC: higher FC of sgACC with the DMN and lower FC of the sgACC with the dorsal anterior cingulate and dorsolateral prefrontal cortex. Second, these subjects will be treated with a 12-week Mindfulness Based Stress Reduction for Teens (MBSR-T) intervention, designed to increase daily mindfulness, meditation skills, and awareness of emotional dysregulation in response to stressors. We hypothesize that youth with BD NOS will experience decreases in depressive symptoms and degree of mood dysregulation, and increases in functioning and degree of mindfulness practice. Furthermore, we anticipate that FC of sgACC with DMN will decrease and FC of sgACC with dorsal structures will increase, as will left hippocampal volume. Consistent with the NIMH Strategic Plan, this study will examine neurobiological risk factors for mood disorder development in youth and neural mechanisms of a novel intervention that has potential for prevention, while creating additional opportunities for mentoring the next generation of clinical researchers in the field of pediatric mood disorder prevention.