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）知之甚少，但最近的数据表明，儿科双相情感障碍（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，目前占精神病院所有未成年人出院人数的20%。确定儿童是否患有双相障碍是有问题的，因为目前的精神病学分科完全基于临床病史，而从儿童和青少年身上推断出来比从成人身上推断出来要困难得多。因此，迫切需要确定双相障碍的生物行为标志物，特别是指出哪些儿童将发展为具有明显躁狂发作的全面双相障碍，哪些儿童将保持亚综合征（后者称为“未另行指定”的双相障碍[NOS]）。本研究的挑战和目标是识别BD转化的生物行为标志物。我们的中心假设是，通过(a)前额皮质-杏仁核-纹状体回路的神经改变介导(b)认知灵活性和面部处理的行为表现，(c)遗传和(d)个人因素调节，bd -转换者将与亚综合征BD-NOS患者区分开来。研究方法：为了验证这一假设，我们将研究年龄在18-25岁之间的年轻人，他们从小就被布朗大学的双相情感障碍青年研究的过程和结果（COBY）网站跟踪，以便将诊断的回顾性回忆偏差降到最低。具体来说，我们将研究：(1)从亚症状型BD- nos转变为全面型BD （BD-converters）的患者，(2)仍然患有BD- nos的患者（BD- nos），以及(3)仍然患有I型BD （BD- remain）的患者。我们还将招募一组年龄/性别匹配的健康成人对照组（HC）。我们将收集行为任务（反转学习，面部处理），多模态磁共振成像（MRI，包括结构MRI，功能MRI， DTI，神经连通性），以及使用冥想分析原理评估的遗传数据。意义：所提出的研究具有创新性和重要意义，因为它们首次将多学科神经科学方法用于前瞻性表型样本，以确定从BD- nos转化为全面BD和剩余亚综合征BD- nos的生物行为标记物。这种双相障碍转化的生物行为标记物最终可以在个性化医疗方法中增加临床病史，从而改善（更具体或更早）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.