Prefrontal-Amygdala Circuitry In Young Children with Severe Emotion Dysregulation

描述（由申请人提供）：背景和理由：迫切需要改进以易怒和频繁、损害性愤怒为形式的严重情绪失调幼儿的分类学分类和治疗。尽管缺乏与成人表型纵向关联的证据，但这些儿童中的许多人被诊断为儿童双相情感障碍。或者，这些孩子可能被诊断为多动症和/或对立违抗性障碍，导致治疗可能不能直接解决情绪失调的高度损害症状。经验证据表明，背前扣带皮层（dACC）通过与杏仁核的相互连接来调节情绪，而这些区域之间功能连接的破坏与情绪障碍有关。与NIMH战略计划一致，该研究的总体目标是确定幼儿严重情绪失调的生物行为机制，最终目标是使用这种标记物来为这一高度受损群体的分类和治疗提供信息。创新的神经影像学和行为方法将用于验证以下假设：假设1)与正常发育的儿童和没有严重情绪失调的ADHD儿童相比，患有严重情绪失调的幼儿在dacc -杏仁核回路中表现出较弱的内在功能连接。包括一个精神病学的比较组提供了一个严格的测试，提出的情绪调节回路中断的综合征特异性。假设2)在幼儿中，无论群体如何，较弱的dacc -杏仁核内在功能连通性将与较差的情绪调节相关，这是用气球游戏测量的，气球游戏是一种为幼儿设计的新范式，在两种不同情绪表达调节需求的条件下引起挫折。弥散张量成像（DTI）将用于探讨dacc -杏仁核功能连通性与白质完整性之间的关系，并检查组间差异。因为我们不期望所有的孩子都能在扫描仪中进行这些额外的扫描，所以这个目标是探索性的。设计：168名儿童（5-9岁）将分成三组（每组N=56）：(1)有严重情绪失调的儿童，以频繁的、损害性的愤怒为指标；(2) ADHD患儿，但无严重情绪失调；(3)典型的发展控制。各组将根据儿童的性别、年龄、智商、社会经济地位、种族和惯用手进行分组匹配。评估包括：(1)临床评估，包括全面系统的诊断评估，以及家长和老师打分的行为量表；（二）气球游戏；以及(3)静息状态功能扫描、结构序列和可选DTI扫描。研究假设的证实将为幼儿严重情绪失调的生物行为标记提供重要证据，为未来的工作提供基础，旨在利用这种标记来告知这一高度受损群体的分类和治疗。

DESCRIPTION (provided by applicant): Background and Rationale: There is an urgent need for improving the nosological classification and treatment of young children with severe emotion dysregulation, in the form of irritability and frequent, impairing rages. Many of these children are diagnosed with pediatric bipolar disorder despite a lack of evidence for a longitudinal association with the adult phenotype. Alternatively, these children may be diagnosed with ADHD and/or oppositional defiant disorder, leading to treatments that may not directly address the highly impairing symptoms of emotion dysregulation. Empirical evidence suggests that the dorsal anterior cingulate cortex (dACC) regulates emotion through reciprocal connections with the amygdala, and that disruption of the functional connectivity between these regions is associated with mood disorders. Consistent with the NIMH Strategic Plan, the overall aim of the proposed study is to identify a biobehavioral mechanism underlying severe emotion dysregulation in young children, with the ultimate goal of using such a marker to inform classification and treatment of this highly impaired group. Innovative neuroimaging and behavioral methods will be used to test the following hypotheses: Hypothesis 1) Young children with severe emotion dysregulation will exhibit weaker intrinsic functional connectivity in the dACC-amygdala circuit compared to typically developing children and to children with ADHD without severe emotion dysregulation. Including a psychiatric comparison group provides a stringent test of the syndromal specificity of the proposed disruptions in emotion regulation circuitry. Hypothesis 2) In young children, regardless of group, weaker dACC-amygdala intrinsic functional connectivity will be associated with poorer emotion regulation as measured using the Balloons Game, a novel paradigm designed for young children that elicits frustration under two conditions that vary the demand for regulation of emotional expression. Diffusion tensor imaging (DTI) will be used to explore the relationship between dACC-amygdala functional connectivity and white matter integrity, and examine group differences. Because we do not expect all children to be able to remain in the scanner for these additional scans, this aim is exploratory. Design: 168 children (ages 5-9) will form three groups (N=56 each): (1) children with severe emotion dysregulation as indexed by frequent, impairing rages; (2) children with ADHD without severe emotion dysregulation; and (3) typically developing controls. Groups will be group-matched for child sex, age, IQ, socioeconomic status, ethnicity, and handedness. Assessments include: (1) a clinical evaluation consisting of a comprehensive systematic diagnostic assessment, and parent- and teacher-rated behavior scales; (2) the Balloons Game; and (3) a resting state functional scan, a structural sequence, and an optional DTI scan. Confirmation of study hypotheses will provide important evidence of a biobehavioral marker of severe emotion dysregulation in young children that will provide the basis for future work aimed at using such a marker to inform the classification and treatment of this highly impaired group. PUBLIC HEALTH RELEVANCE: Prefrontal-Amygdala Circuitry in Young Children with Severe Emotion Dysregulation Young children with significant irritability and frequent, severe rages are often diagnosed with, and treated for, bipolar disorder although recent studies suggest that many of these children are being misdiagnosed. Using a new imaging method to measure the spontaneous activity of the brain, and a computer game that assesses emotion regulation, we propose to test a specific theory of why some young children (ages 5-9) have such mood symptoms. If successful, we will have identified a specific brain circuit that is associated with irritability and frequent rages that can be used in future studies to better match treatments for these troubled children.