The Phenomenology And Neurophysiology Of Juvenile Bipolar Disorder

本研究的目的是确定儿童和青少年双相情感障碍（BD）症状的脑机制。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，或表现情绪的面孔。大约100名患者和匹配的对照者已经在一系列这样的范例上进行了评估。综上所述，这些数据表明，患有BPD的儿童很难调整自己的行为，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，两个任务测试他们抑制主导运动反应并启动另一个运动反应的能力，一个任务评估他们在挫折背景下的行为。此外，我们的数据表明，患有BPD的儿童难以准确识别面部情绪。通过功能性MRI，我们发现杏仁核过度活跃与面部标记缺陷有关，前额叶和纹状体异常与运动抑制和反应灵活性缺陷有关。基于这些发现，我们正在启动基因研究，旨在确定与双相情感障碍相关的多态性与功能性MRI识别的大脑激活异常模式之间的关联。此外，我们已经开始研究那些因为父母或兄弟姐妹中有人患有BPD而有患该疾病风险的儿童。本研究的目的是确定我们确定的行为缺陷是否具有家族性，因此可能是BPD的候选内表型。到目前为止，我们的数据表明，有双相障碍风险的青少年在面部情绪识别方面表现出与双相障碍青少年相似的缺陷，这表明这种缺陷可能与疾病的原因有关，而不仅仅是孩子生病的结果。此外，今年我们招募了ADHD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，以确定在执行面部情绪识别和反应灵活性任务时，这些组的大脑功能如何不同。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基因样本用于未来的研究，并对患者进行纵向随访（临床和结构MRI扫描）。

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).