Brain and Behavior Mechanisms of Irritability and Cognitive Flexibility in Children

儿童烦躁和认知灵活性的大脑和行为机制

基本信息

批准号：
9211458
负责人：
DANIEL P DICKSTEIN
金额：
$ 54.89万
依托单位：
EMMA PENDLETON BRADLEY HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-12 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9211458
关键词：
3-Dimensional Address Adolescent Adult Affective Age Aggressive behavior Android Antipsychotic Agents Attention deficit hyperactivity disorder Autistic Disorder Base of the Brain Behavior Behavioral Behavioral Mechanisms Biological Bipolar Disorder Caring Categories Child Childhood Chronic Classification Clinical Cognitive Cognitive remediation Congresses Corpus striatum structure Data Dependence Diagnosis Diagnostic Diagnostic and Statistical Manual of Mental Disorders Diffusion Dimensions Disease Ecological momentary assessment Educational workshop Equation Euphoria Evaluation Frequencies Frustration Functional Magnetic Resonance Imaging Gaussian model Generalized Anxiety Disorder Goals Impaired cognition Impairment Individual Interview Lead Learning Link Manic Measures Mediating Methodology Modeling National Institute of Mental Health Oppositional Defiant Disorder Outpatients Parents Participant Pharmaceutical Preparations Phenotype Prefrontal Cortex Psychiatric therapeutic procedure Psychiatry Psychopathology Punishment Questionnaires Randomized Controlled Trials Recording of previous events Research Research Domain Criteria Rest Reversal Learning Rewards Sampling Scanning Schools Severities Signal Transduction Stimulus Suicide Symptoms Task Performances Techniques Testing Time Veins Work Youth affective neuroscience associated symptom base behavior test biobehavior brain behavior effective therapy flexibility functional disability gray matter hypomania improved innovation meetings novel novel diagnostics peer precision medicine response severe mood dysregulation single episode major depressive disorder social spectrograph symptom cluster white matter

项目摘要

PROJECT SUMMARY/ABSTRACT: Background: Irritability is: the most common reason children and adolescents are brought for psychiatric care, associated with significant impairment in childhood and subsequently in adulthood, a symptom found in many DSM-categorical disorders—yet we have no clinically useful, validated bio-behavioral marker or measure to guide clinician's diagnosis or treatment of children presenting with irritability. To address this problem, the 2014 NIMH Pediatric Irritability Workshop and the 2015 1st Congress on Pediatric Irritability heralded the need for greater research on brain/behavior mechanisms of pediatric irritability, including studies in trans-diagnostic samples drawn across the range of impairment, rather than a single DSM disorder and testing multiple dimensional irritability assessments. Previously, we have investigated the brain/behavior alterations underlying cognitive flexibility—defined as behavioral adaptation in response to changing rewards and punishments—as one potential mechanism underlying irritability in children meeting categorical definitions of bipolar disorder (episodes of euphoria and irritability) or severe mood dysregulation (chronic irritability) vs. controls. Now, we seek to take the next step in this line of research. The objective of this application is to define the brain/behavior mechanism-based sub-types of irritability and cognitive flexibility in a trans-diagnostic sample of children ages 8-12 drawn across the range of impairment. Our central methodology is to test how circuit and behavior alterations in cognitive flexibility identify different sub-types of irritability, using single time point irritability questionnaires/interviews and a novel multi-time point irritability ecological momentary assessment (EMA) Android app, and harnessing novel computational psychiatry analytic techniques to determine which model best explains brain/behavior-based clusters of irritability. Our central hypothesis is that all irritability does not result from a single mechanism; rather unique symptom clusters of irritability result from specific PFC- temporo-striatal circuit alterations mediating cognitive flexibility. The rationale for this proposal is that greater understanding of the biological mechanisms underlying cognitive flexibility and irritability symptoms will lead to novel brain-based classification and treatments for children suffering from irritability. Our study is innovative because we will be the first to identify the brain/behavior mechanisms underlying irritability and cognitive flexibility using (1) a trans-diagnostic sample of children drawn across levels of care and impairment, rather than DSM categorical disorder(s), (2) novel EMA-irritability app, (3) computational psychiatry analytic techniques, and (4) fMRI/behavioral tasks drawn from BD/SMD research plus the RDoC matrix. Our study is both significant and clinically meaningful because greater understanding of the brain/behavior mechanisms of irritability and cognitive flexibility is critical to achieving the ultimate goal of a precision medicine approach for irritability—whereby bio-behavioral markers (scans and tests) are used for more specific/earlier classification and diagnosis plus biologically-guided treatment (e.g., medications, cognitive remediation, and TMS/TDCS).

项目概要/摘要：背景：易怒是：儿童和青少年被送去接受精神病治疗的最常见原因护理，与童年时期和随后的成年期的严重损害有关，这是一种在以下情况中发现的症状许多 DSM 分类疾病——但我们没有临床上有用的、经过验证的生物行为标志物或测量方法指导临床医生对出现烦躁的儿童进行诊断或治疗。 2014 年 NIMH 儿科烦躁研讨会和 2015 年第一届儿科烦躁大会预示了这一需求对儿科烦躁的大脑/行为机制进行更深入的研究，包括跨诊断研究在整个损伤范围内抽取样本，而不是单一 DSM 障碍并测试多个此前，我们研究了潜在的大脑/行为改变。认知灵活性——定义为响应不断变化的奖励和惩罚的行为适应——如符合双相情感障碍分类定义的儿童烦躁的一种潜在机制（欣快感和烦躁的发作）或严重的情绪失调（慢性烦躁）现在，我们与对照组进行比较。寻求在这一领域的研究中采取下一步行动，该应用程序的目标是定义跨诊断样本中基于大脑/行为机制的烦躁性和认知灵活性亚型我们的核心方法是测试 8 至 12 岁的儿童的障碍范围。认知灵活性的行为改变使用单一时间点识别不同的烦躁亚型烦躁问卷/访谈和新颖的多时间点烦躁生态瞬时评估 (EMA) Android 应用程序，并利用新颖的计算精神病学分析技术来确定哪些模型最好地解释了基于大脑/行为的烦躁情绪。我们的中心假设是所有烦躁情绪都是如此。不是由单一机制引起的；而是由特定的 PFC- 引起的独特的烦躁症状群。颞纹状体回路的改变调节认知灵活性。该提议的基本原理是：更好地了解认知灵活性和烦躁症状背后的生物机制将我们的研究是针对烦躁儿童的基于大脑的新分类和治疗。创新，因为我们将是第一个确定易怒和行为背后的大脑/行为机制的人认知灵活性，使用（1）跨护理和损伤级别抽取的儿童跨诊断样本，而不是 DSM 分类障碍，(2) 新颖的 EMA 烦躁应用程序，(3) 计算精神病学分析技术，以及（4）来自 BD/SMD 研究的 fMRI/行为任务以及 RDoC 矩阵。既重要又具有临床意义，因为可以更好地了解大脑/行为机制烦躁性和认知灵活性的改善对于实现精准医学方法的最终目标至关重要烦躁——生物行为标记（扫描和测试）用于更具体/更早的分类诊断加上生物学指导的治疗（例如药物、认知矫正和 TMS/TDCS）。