Phenomenology/Neurophysiology Of Juvenile Bipolar Dis

本研究有两个具体的目的：1）使用纵向的，客观的技术来描述早发性双相情感障碍（BPD）的临床表现; 2）确定双相情感障碍儿童和青少年的神经生理学和神经心理学相关因素。目标#2的一个特别关注点是确定行为范式，其评估在BPD的病理生理学中重要的心理过程，并且可以用于随后的fMRI研究（以识别患者的功能障碍性神经回路）或家族研究（以识别疾病的行为和生物学标记，即内在表型）。大约50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很明显，这是一项测试他们抑制主导运动反应并启动另一种反应的能力的任务，也是一项评估他们在挫折背景下行为的任务。此外，我们的数据表明，BPD儿童难以准确识别面部情绪。我们假设这些缺陷是由于前额叶-纹状体-杏仁核回路功能障碍，并使用功能磁共振成像，我们已经获得了一些神经影像学数据来支持这一假设。基于这些发现，我们正在启动一项针对BPD成人及其儿童的研究，他们有患病的风险。该研究的目的是确定我们所确定的行为缺陷是否是家族性的，因此是否可能是BPD的候选内表型。此外，今年我们开始招募ADHD儿童作为BPD儿童的精神对照组。最后，我们继续评估家庭成员的精神状态，从患者和父母那里收集遗传样本用于未来的研究，并纵向跟踪患者（临床和结构MRI扫描）4年。

This study has two specific aims: 1) to use longitudinal, objective techniques to characterize the clinical manifestations of early-onset bipolar disorder (BPD); and 2) to identify neurophysiological and neuropsychological correlates of affective dysregulation in bipolar children and adolescents. A particular focus of aim #2 is the identification of behavioral paradigms that assess psychological processes that are important in the pathophysiology of BPD, and that can be used either in subsequent fMRI studies (to identify dysfunctional neural circuitry in patients) or in family studies (to identify behavioral and biological markers of the illness i.e. endophenotypes). Approximately 50 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, a task 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. We hypothesize that these deficits are due to dysfunction in prefrontal-striatal-amygdala circuitry and, using fMRI, we have obtained some neuroimaging data to support that hypothesis. Based on these findings, we are initiating a study of adults with BPD and their children, who are at risk for the illness. The goal of that study is to ascertain whether the behavioral deifcits that we identified are familial and therefore may be candidate endophenotypes for BPD. In addition, this year we began recruiting children with ADHD as a psychiatric comparison group for children with BPD. 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) for 4 years.