Bio-Behavioral Markers of Bipolar Conversion

描述（由申请人提供）：虽然我们对儿童和青少年的双相情感障碍（BD）了解较少，但最近的数据表明，儿科BD（PBD）是一个新兴的健康问题，其发病率在过去十年中上升了40倍，目前占精神病医院出院的所有未成年人的20%。确定儿童是否患有BD是有问题的，因为目前的精神疾病分类学完全基于临床病史，这比成人更难从儿童和青少年中引出。因此，迫切需要鉴定BD的生物行为标志物，特别是指示哪些儿童将发展为具有明显躁狂发作的全面BD，以及哪些将保持亚综合征（后者称为BD“未另行说明”[NOS]）。本BRAINS R 01研究应用程序的挑战和目标是识别BD转换的生物行为标志物。我们的中心假设是，通过（a）调节（B）认知灵活性和面部处理的行为表现的前额叶皮层-杏仁核-纹状体回路的神经改变，以及（c）遗传和（d）个人因素的调节，可以将BD转换者与那些仍然是亚综合征BD-NOS的人区分开来。研究方法：为了验证这一假设，我们将研究18-25岁的年轻人，他们从小就被布朗大学的双相青年研究（COBY）的课程和结果所跟踪，以便将关于诊断的回顾性回忆偏差降至最低。特别是，我们将研究：（1）那些从亚综合征BD-NOS转换为全面BD（BD转换器），（2）那些仍然BD-NOS（BD-NOS），和（3）那些仍然BD I型（BD-保持）。我们还将招募一组新的年龄/性别匹配的典型发育健康成人对照（HC）。我们将收集行为任务（反向学习，面部处理），多模态磁共振成像（MRI;包括结构MRI，功能MRI，DTI，神经连接），以及使用冥想分析原理评估的遗传数据。重要性：拟议的研究是创新和重要的，因为它们代表了第一次将多学科神经科学方法用于前瞻性表型样本中，以确定从BD-NOS转化为全面BD的生物行为标志物，以及剩余的亚综合征BD-NOS。这种BD转换的生物行为标志物最终可以在个性化医学方法中增加临床病史，从而改善（更特异或更早）诊断和治疗。

DESCRIPTION (provided by applicant): Although we know less about bipolar disorder (BD) in children and adolescents, recent data indicate that pediatric BD (PBD) is a burgeoning health problem whose incidence has risen 40-fold in the past decade and now accounts for 20% of all minors discharged from psychiatric hospitals. Determining if a child has BD or not is problematic because current psychiatric nosology is based entirely on clinical history, which is considerably more difficult to elicit from children and adolescents than from adults. Thus, there is a pressing need to identify bio-behavioral markers of BD, especially to indicate which children will develop full-blown BD with distinct episodes of mania, and which will remain sub-syndromal (the latter known as BD "not otherwise specified" [NOS]). THE CHALLENGE AND GOAL OF THIS BRAINS R01 RESEARCH APPLICATION is to identify bio-behavioral markers of BD conversion. OUR CENTRAL HYPOTHESIS is that BD-converters will be differentiable from those who remained sub-syndromal BD-NOS by (a) neural alterations in a prefrontal cortex- amygdala-striatal circuit that mediate (b) behavioral performance on cognitive flexibility and face processing, as moderated by (c) genetic and (d) personal factors. RESEARCH METHOD: To test this hypothesis, we will study young adults ages 18-25 years who have been followed since childhood by Brown University's site of the Course and Outcome of Bipolar Youth study (COBY), so that retrospective recall bias about diagnosis will be minimized. In particular, we will study: (1) those who converted from sub-syndromal BD-NOS to full-blown BD (BD-converters), (2) those who remained BD-NOS (BD-NOS), and (3) those who remained BD type I (BD- remain). We will also recruit a new group of age/sex matched typically-developing healthy adult controls (HC). We will collect behavioral task (reversal learning, face processing), multi-modal magnetic resonance imaging (MRI; including structural MRI, functional MRI, DTI, neural connectivity), and genetic data evaluated using principles of meditational analysis. SIGNIFICANCE: The proposed studies are innovative and significant because they represent the first time that multi-disciplinary neuroscience methods will be used in a prospectively phenotyped sample to identify bio-behavioral markers of conversion from BD-NOS to full-blown BD, and with remaining sub-syndromal BD-NOS. Such bio-behavioral markers of BD conversion could ultimately augment clinical history in a personalized medicine approach, resulting in improved (more specific or earlier) diagnosis and treatment.