The Phenomenology And Neurophysiology Of Juvenile Bipolar Disorder

青少年双相情感障碍的现象学和神经生理学

• 批准号: 7594530
• 负责人: Ellen Leibenluft
• 金额: $ 154.44万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7594530
• 关键词: Adolescent; Amygdaloid structure; Attention deficit hyperactivity disorder; Behavior; Behavioral; Behavioral Paradigm; Bipolar Disorder; Borderline Personality Disorder; Brain; Bronchopulmonary Dysplasia; Child; Childhood; Corpus striatum structure; Data; Emotional; Emotions; Environment; Face; Family member; Frustration; Functional Magnetic Resonance Imaging; Future; Genetic; Genetic Polymorphism; Goals; Hyperactive behavior; Label; MRI Scans; Mediating; Motor; Parents; Patients; Pattern; Phase; Pliability; Process; Punishment; Purpose; Recruitment Activity; Research; Rewards; Risk; Sampling; Siblings; Symptoms; Techniques; Testing; Youth; affective neuroscience; base; comparison group; design; disorder control; emotional stimulus; endophenotype; follow-up; neural circuit; neurophysiology; outcome forecast; response

This purpose of this study to identify brain mechanisms mediating the symptoms of bipolar disorder (BD)in children and adolescents. To do this, patients and controls complete standardized behavioral paradigms designed to assess responses to emotional stimuli, such as reward and punishment, or faces displaying emotion. Approximately 100 patients and matched controls have been assessed on a battery of such paradigms. Taken together, these data indicate that children with BPD have difficulty adapting their behavior in response to changes in emotional stimuli in their environment. These deficits are evident on response reversal tasks, two tasks testing their ability to inhibit a dominant motor response and initiate another, and a task that assesses their behavior in the context of frustration. In addition, our data indicate that children with BPD have difficulty identifying facial emotion accurately. Using functional MRI, we have identified amygdala hyperactivity that is associated with the face labeling deficit, and prefrontal and striatal abnormalities associated with deficits in motor inhibition and response flexibility. Based on these findings, we are initiating genetic studies aimed at identifying associations between polymorphisms associated with bipolar disorder and abnormal patterns of brain activation identified with functional MRI. In addition, we have begun a study of children who are at risk for BPD because they have a parent or sibling with the illness. The goal of this study is to ascertain whether the behavioral deficits that we identified are familial and therefore may be candidate endophenotypes for BPD. Thus far, our data indicate that youth at risk for BD show deficits in face emotion identification similar to those seen in youth with BD, indicating that such deficits may be related to causes of the illness, rather than simply being a result of the child being ill. In addition, this year we recruited children with ADHD as a psychiatric comparison group for children with BPD, and are currently analyzing functional MRI data to ascertin how brain function may differ among these groups while performing face emotion identification and response flexibility tasks. Finally, we continue to assess the psychiatric status of family members, bank genetic samples from patients and parents for use in future studies, and follow the patients longitudinally (clinically and with structural MRI scans).

本研究的目的是确定介导儿童和青少年双相情感障碍（BD）症状的大脑机制。为了做到这一点，患者和对照组完成了标准化的行为范式，旨在评估对情绪刺激的反应，如奖励和惩罚，或面部表情。 大约100例患者和匹配的对照组进行了评估电池的这种模式。 综上所述，这些数据表明，BPD儿童很难适应他们的行为，以应对环境中情绪刺激的变化。 这些缺陷在反应逆转任务中表现得很明显，这两项任务测试了他们抑制主导运动反应并启动另一种反应的能力，而另一项任务则评估了他们在沮丧背景下的行为。 此外，我们的数据表明，BPD儿童难以准确识别面部情绪。 使用功能性MRI，我们已经确定了杏仁核过度活跃与面部标记缺陷，以及前额叶和纹状体异常与运动抑制和反应灵活性缺陷。 基于这些发现，我们正在启动遗传学研究，旨在确定与双相情感障碍相关的多态性和功能性MRI确定的大脑激活异常模式之间的关联。 此外，我们已经开始了一项研究的儿童谁是在风险BPD，因为他们有一个与疾病的父母或兄弟姐妹。 本研究的目的是确定我们确定的行为缺陷是否是家族性的，因此可能是BPD的候选内表型。到目前为止，我们的数据表明，有BD风险的青少年在面部情绪识别方面表现出与BD青少年相似的缺陷，这表明这种缺陷可能与疾病的原因有关，而不仅仅是儿童生病的结果。 此外，今年我们招募了患有ADHD的儿童作为BPD儿童的精神病学对照组，目前正在分析功能性MRI数据，以确定这些群体在执行面部情绪识别和反应灵活性任务时大脑功能可能存在差异。最后，我们继续评估家庭成员的精神状态，从患者和父母那里获得遗传样本以供未来研究使用，并纵向跟踪患者（临床和结构MRI扫描）。