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

• 批准号: 10059261
• 负责人: DANIEL P DICKSTEIN
• 金额: $ 47.66万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059261
• 关键词: 3-Dimensional; Address; Adolescent; Adult; Affective; Age; Aggressive behavior; Antipsychotic Agents; Attention deficit hyperactivity 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; Structure; Suicide; Symptoms; Task Performances; Techniques; Testing; Time; Veins; Work; Youth; adolescent with autism spectrum disorder; affective neuroscience; associated symptom; autism spectrum disorder; 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; smartphone Application; social; spectrograph; symptom cluster; white matter

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).

项目摘要/摘要： 背景：烦恼是：儿童和青少年是为精神科带来的最常见原因 护理，与儿童期以及随后在成年期的重大损害相关，这是一种症状 许多DSM类别疾病 - 但是，我们没有临床上有用的，经过验证的生物行为标记或测量 指导临床上的诊断或治疗易怒的儿童。为了解决这个问题， 2014年NIMH儿科烦恼研讨会和2015年第1届小儿烦恼大会预示了需求 为了对小儿易怒的大脑/行为机制进行更多的研究，包括对反诊断的研究 在损害范围内绘制的样品，而不是单个DSM障碍并测试多个 维度易怒评估。以前，我们已经调查了大脑/行为的改变 认知灵活性（因改变奖励和惩罚而被定义为行为适应） 儿童中易怒的一种潜在机制，符合躁郁症的分类定义 （欣快和烦躁的发作）或严重的情绪失调（慢性易怒）与对照。现在，我们 寻求在这一研究中迈出下一步。此应用的目的是定义 基于大脑/行为机制的子类型在反诊断样本中的易怒和认知灵活性 8-12岁的儿童在损害范围内吸引。我们的中心方法是测试电路和如何 认知灵活性的行为改变使用单个时间点确定了不同的亚型烦躁的子类型 烦躁的问卷/访谈和一种新颖的多时间烦躁不良生态瞬时评估 （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种 模型最能解释易怒的基于大脑/行为的集群。我们的中心假设是所有烦躁 不是由单个机制引起的；特定的PFC-造成了相当独特的易怒症状簇 颞纹状体电路改变介导认知灵活性。该提议的理由是 对认知灵活性和易怒症状的生物学机制的更多了解将 导致新颖的基于大脑的分类和治疗患有烦躁的儿童。我们的研究是 创新性，因为我们将是第一个确定易怒和行为机制和行为机制的人 使用（1）跨护理和障碍的儿童的反诊断样本的认知灵活性， 而不是DSM分类障碍（S），（2）新颖的EMA-riritability应用程序，（3）计算精神病学分析 技术和（4）fMRI/行为任务从BD/SMD研究以及RDOC矩阵中绘制。我们的研究是 意义重大和临床意义，因为对大脑/行为机制的了解更大 易怒和认知灵活性对于实现精确医学方法的最终目标至关重要 烦躁不良 - 在任何特定/更早的分类中使用生物行为标记（扫描和测试） 和诊断加生物学引导的治疗（例如药物，认知补救和TMS/TDCS）。

项目成果

Systematic Review: White Matter Microstructural Organization in Adolescents With Depression.

系统评价：抑郁症青少年的白质微观结构组织。

• DOI: 10.1016/j.jaacop.2023.08.006
• 发表时间: 2023
• 期刊: JAACAP open
• 作者: Radoeva,PetyaD;Milev,VictorT;Hunt,JeffreyI;Legere,ChristopherH;Deoni,SeanCL;Sheinkopf,StephenJ;Mazefsky,CarlaA;Philip,NoahS;Dickstein,DanielP
• 通讯作者: Dickstein,DanielP