Prefrontal-Amygdala Circuitry In Young Children with Severe Emotion Dysregulation

描述（由申请人提供）：背景和原理：迫切需要改善患有严重情绪失调的幼儿的疾病分类和治疗，这些情绪失调表现为易怒和频繁的损害性愤怒。尽管缺乏与成人表型纵向相关的证据，但这些儿童中的许多人被诊断为儿童双相情感障碍。或者，这些儿童可能被诊断患有ADHD和/或对立违抗性障碍，导致治疗可能无法直接解决情绪失调的高度损害症状。经验证据表明，背侧前扣带皮层（dACC）通过与杏仁核的相互连接来调节情绪，并且这些区域之间的功能连接的中断与情绪障碍有关。与NIMH战略计划一致，拟议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，最终目标是使用这样的标记来告知这个高度受损群体的分类和治疗。创新的神经影像学和行为学方法将用于测试以下假设：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。包括精神病学比较组提供了对情绪调节回路拟议中断的综合征特异性的严格测试。假设2）在幼儿中，无论是哪一组，较弱的dACC-杏仁核内在功能连接将与较差的情绪调节相关，这是使用情绪调节游戏测量的，这是一种为幼儿设计的新范式，在两种不同的情绪表达调节需求条件下激发挫折感。将使用扩散张量成像（DTI）探索dACC-杏仁核功能连接与白色物质完整性之间的关系，并检查组间差异。因为我们并不期望所有儿童都能留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。设计图：168名儿童（5-9岁）将分成三组（每组N=56）：（1）患有严重情绪失调的儿童，以频繁的损害性愤怒为指标;（2）患有ADHD但没有严重情绪失调的儿童;以及（3）通常发展中的对照组。各组将根据儿童性别、年龄、智商、社会经济地位、种族和利手进行组匹配。评估包括：（1）临床评估，包括全面系统的诊断评估，以及家长和教师评定的行为量表;（2）智力游戏;（3）静息状态功能扫描，结构序列和可选的DTI扫描。研究假设的确认将提供重要的证据，生物行为标记的严重情绪失调的幼儿，将提供基础，为未来的工作，旨在使用这样的标记，告知这个高度受损的群体的分类和治疗。

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.