Bio-Behavioral Markers of Bipolar Conversion

双极转换的生物行为标志

基本信息

批准号：
8280386
负责人：
DANIEL P DICKSTEIN
金额：
$ 33.4万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-18 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8280386
关键词：
Accounting Address Adolescent Adult Age American Amygdaloid structure Awareness Behavior Behavioral Bipolar Disorder Brain Brain scan Child Childhood Circadian Rhythms Clinical Cognitive Comorbidity Corpus striatum structure Data Development Diagnosis Diagnostic Disease Early Diagnosis Emotional Evaluation Expenditure Face Face Processing Functional Magnetic Resonance Imaging Genes Genetic Goals HTR2A gene Health Healthcare Heterogeneity Incidence Irritable Mood Magnetic Resonance Imaging Manic Mediating Medicine Methods Minor Monoamine Oxidase Morbidity - disease rate Neurosciences Outcome Participant Performance Pharmaceutical Preparations Phenotype Prefrontal Cortex Psychiatric Hospitals Psychiatry Psychotherapy Public Health Recording of previous events Recruitment Activity Research Reversal Learning Rewards Risk Sampling Site Specific qualifier value Stimulus Symptoms TDO2 gene Testing Thinking Time To specify Translating Tryptophan 5-monooxygenase Universities Work Youth age group base childhood bipolar disorder clinical practice disease classification endophenotype flexibility improved innovation mortality prognostic promoter relating to nervous system response serotonin receptor serotonin transporter sex trend young adult

项目摘要

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.

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增加了 40 倍，目前已报告占精神病院出院未成年人的 20%。确定儿童是否患有双相情感障碍是有问题的，因为当前的精神病学分类学完全基于临床病史，从儿童和青少年身上获取临床病史比从成人身上获取要困难得多。因此，迫切需要确定 BD 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 BD，哪些儿童将保持亚综合征（后者称为 BD“未另行指定”） “[NOS]）。本 BRAINS R01 研究应用的挑战和目标是确定 BD 转化的生物行为标记。我们的中心假设是，BD 转换者与那些仍处于亚综合征 BD-NOS 状态的人的区别在于：(a) 前额皮质-杏仁核-纹状体回路中的神经改变，介导 (b) 认知灵活性和面部处理方面的行为表现，由 (c) 遗传因素和 (d) 个人因素调节。研究方法：为了检验这一假设，我们将对 18-25 岁的年轻人进行研究，他们自童年起就被布朗大学双相情感障碍青少年的过程和结果研究 (COBY) 网站跟踪，以便消除有关诊断的回顾性回忆偏差。最小化。我们将特别研究：(1) 从亚综合征 BD-NOS 转变为成熟 BD 的人（BD 转换器），(2) 仍保留 BD-NOS 的人 (BD-NOS)，以及 (3)那些仍然保留 BD I 型（BD- 保留）的人。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（逆转学习、面部处理）、多模态磁共振成像（MRI；包括结构MRI、功能MRI、DTI、神经连接）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意义，因为它们代表了首次在前瞻性表型样本中使用多学科神经科学方法来识别从 BD-NOS 转化为成熟 BD 的生物行为标志物，并且剩余的亚综合征 BD-NOS。这种 BD 转化的生物行为标志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。