The Phenomenology and Neurophysiology of Juvenile Bipolar Disorder

自本项目开始以来，我们已经筛选了3000多名受试者进行这项研究。我们招募了大约215名双相情感障碍（BD）青年，320名有BD风险的受试者，因为他们有父母或兄弟姐妹患有这种疾病，以及120名BD成人。今年，约有15名新受试者入组。 今年，我们继续我们的工作，旨在确定儿童BD的脑机制;比较青少年和成人BD的脑功能，以便开始了解疾病如何随着时间的推移发展;并比较BD家族风险的青少年与BD和低风险的青少年的脑功能，以促进预防干预措施的最终发展。 关于我们对脑机制介导BD的研究，大部分工作不仅包括将BD青年与健康青年进行比较，还包括将BD青年与严重慢性易怒的人进行比较（所谓的破坏性情绪失调或DMDD人群，见年度校内研究报告ZIAMH 002786）。比较BD和DMDD的青少年是很重要的，因为特别是在DMDD被纳入DSM-5之前，易怒的儿童经常在社区中被诊断为BD，尽管他们没有躁狂发作史。这种潜在的误诊是重要的，因为与严重的慢性易怒相比，青少年BD是用副作用负担高的药物治疗的。 虽然在DSM-5中添加DMDD可能降低了易激惹儿童被误诊为BD的程度，但区分这些临床表现背后的大脑机制非常重要，因为诊断之间的差异可能与治疗方法有关。 在我们的双相情感障碍相关人群（成人BD，青少年BD，青少年BD风险）中，面部情绪处理一直是我们工作的主要焦点。这是因为准确标记面部情绪的缺陷，以及面部情绪记忆的缺陷，不仅存在于BD患者中，而且存在于处于疾病风险中的青年中。这些发现表明，这种缺陷，在面对情绪标签和记忆是潜在的内表型的BD。去年，我们发表了一篇论文，证明了当患有BD和DMDD的年轻人标记情绪面孔时，与易怒相关的神经机制在诊断中有所不同。今年，我们进行了一项研究，目前正在分析其结果。 这项研究旨在复制先前的工作，同时还研究了各组的眼动追踪模式。具体来说，受试者一天在扫描仪中完成面部情绪标记范例，第二天在进行眼动追踪时完成。 在之前发表的研究中，我们发现患有BD的年轻人和那些有患病风险的人在标记情绪面孔时关注眼睛区域的倾向下降。 DMDD组的结果不明确。我们的目标是复制我们以前的成像和眼动追踪结果;检查眼动追踪模式和神经活动之间的潜在关联;并确定DMDD青少年是否有眼动追踪缺陷。 我们对儿童双相情感障碍的研究是富有成效的。 我们的成就包括证明严重的慢性易怒不是BD的儿科表现，而是BD的青年患者，就像患有这种疾病的成年人一样，经历了可定义的躁狂发作。我们确定了面部情绪标记和反应时间的可变性增加作为BD的潜在遗传生物标志物，并探索了介导每个的大脑机制。然而，我们已决定终止该项目，并将我们所有的资源用于青年慢性易怒的研究（见年度报告ZIAMH 002786）。原因是多方面的，包括易怒在年轻人中比BD更常见;关于易怒的研究明显缺乏;并且很少有基于证据的易怒治疗方法。

Since the beginning of this project we have screened over 3000 subjects for this study. We have enrolled approximately 215 youth with bipolar disorder (BD), 320 subjects at risk for BD because they have a parent or sibling with the illness, and 120 adults with BD. This year, approximately 15 new subjects were enrolled. This year we continued our work designed to identify the brain mechanisms underlying BD in children; compare brain function in youth and adults with BD in order to begin to understand how the illness develops over time; and compare brain function in youth at familial risk for BD to those with BD and those at low risk, in order to facilitate the eventual development of preventive interventions. Regarding our work on the brain mechanisms mediating BD, much of that work consists of, not only comparing youth with BD to healthy youth, but also comparing youth with BD to those with severe, chronic irritability (the so-called Disruptive Mood Dysregulation, or DMDD, population, see Annual Intramural Research Report ZIAMH002786). It is important to compare youth with BD and those with DMDD because, particularly before the inclusion of DMDD in the DSM-5, irritable children frequently received the diagnosis of BD in the community, despite not having a history of manic episodes. This potential misdiagnosis is important because, compared to severe, chronic irritability, BD in youth is treated with medications with high side-effect burden. While it is possible that the addition of DMDD to DSM-5 has decreased the extent to which irritable children are misdiagnosed as having BD, nonetheless it is important to differentiate the brain mechanisms underlying each of these clinical presentations, because differences between the diagnoses may be relevant to treatment approaches. Across our bipolar disorder-related groups (adults with BD, youth with BD, youth at risk for BD), face emotion processing has been a major focus of our work. This is because deficits labeling face emotions accurately, as well as deficits in face emotion memory, are present, not only in patients with BD, but also in youth at risk for the disorder. These findings indicate that such deficits in face emotion labeling and memory are potential endophenotypes for BD. Last year we published a paper demonstrating that, when youth with BD and DMDD labeled emotional faces, the neural mechanisms associated with irritability differed across diagnoses. This year, we conducted a study whose results are currently being analyzed. This study was designed to replicate the prior work, while also studying eye tracking patterns across the groups. Specifically, subjects complete the face emotion labeling paradigm in the scanner one day, and the next day complete it while doing eye tracking. In previously published work, we found that youth with BD, and those at risk for the illness, had a decreased tendency to focus on the eye region while labeling emotional faces. Results for the DMDD group were equivocal. Our goal is to replicate both our previous imaging and eye tracking findings; to examine potential associations between eye tracking patterns and neural activity; and to determine whether youth with DMDD have an eye tracking deficit. Our research on pediatric bipolar disorder has been productive. Our accomplishments include demonstrating that severe, chronic irritability is not a pediatric presentation of BD, but that youth with BD, like adults with the illness, experience definable episodes of mania. We identified face emotion labeling and increased variability in reaction time as potential heritable biomarkers of BD, and explored the brain mechanisms mediating each. However, we have decided to terminate this project and devote all of our resources to the study of chronic irritability in youth (see Annual Report ZIAMH002786). The reasons for this are multiple, including the fact that irritability is significantly more common in youth than is BD; there is a marked paucity of research on irritability; and there are very few evidence-based treatments for irritability.