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

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

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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）：尽管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，小儿BD（PBD）是一个新兴的健康问题，在过去的十年中，其发病率在过去的十年中已经上升了40倍，现在占了从精神病医院出院的所有未成年人中的20％。确定儿童是否患有BD是有问题的，因为当前的精神病学疾病完全基于临床病史，这比成人的儿童和青少年更难引起儿童和青少年。因此，迫切需要识别BD的生物行为标记，尤其是指出哪些儿童会以不同的躁狂发作形成全面的BD，并且哪些将保持亚合成（后者被称为BD“不另行指定” [NOS] [nos]））。此大脑R01研究应用的挑战和目标是确定BD转换的生物行为标记。我们的中心假设是，BD转换器将与那些通过（a）在前额叶皮层 - 杏仁核电路中的神经变化保持在（a）介导（b）对认知灵活性和面部处理上的行为表现的神经变化的人，如（c）遗传和（c）遗传因素。研究方法：为了检验这一假设，我们将研究18-25岁的年轻人，这些年轻人自童年以来一直受到布朗大学的课程和双相青年研究结果（COBY）的效果，以便将有关诊断的回顾性回忆偏见最小化。特别是，我们将研究：（1）那些从子合成BD-NOS转换为成熟BD（BD-Converters）的人，（2）那些仍然保持BD-NOS（BD-NOS）的人，以及（3）那些仍然是BD I型I型（BD-剩余）的人。我们还将招募一组新的年龄/性别匹配的组通常开发健康的成人对照（HC）。我们将收集行为任务（逆转学习，面部处理），多模式磁共振成像（MRI；包括结构性MRI，功能性MRI，DTI，神经连接性）以及使用冥想分析原理评估的遗传数据。意义：拟议的研究具有创新性和意义，因为它们代表了第一次将多学科的神经科学方法用于前瞻性表型样品中，以识别从BD-NOS转化为成熟BD的生物行为标记，以及剩余的亚副体积BD-NOS。 BD转化的这种生物行为标记最终可以通过个性化医学方法来增强临床史，从而改善（更具体或更早）的诊断和治疗。