The Phenomenology and Neurophysiology of Juvenile Bipolar Disorder

自从这个项目开始以来，我们已经为这项研究筛选了3000多名受试者。我们招募了大约215名患有双相情感障碍(BD)的青年，320名因父母或兄弟姐妹患有BD而面临BD风险的受试者，以及120名患有BD的成年人。今年，大约有15门新科目被录取。 今年，我们继续我们的工作，旨在确定儿童BD的脑机制；比较青少年和成年人与BD的脑功能，以开始了解疾病如何随着时间的推移而发展；并将BD的家族风险青年与BD和低风险青年的脑功能进行比较，以促进最终制定预防干预措施。 关于我们在调节BD的大脑机制方面的工作，大部分工作包括，不仅将患有BD的青年与健康的青年进行比较，而且将患有BD的青年与患有严重的慢性易怒的青年进行比较(所谓的破坏性情绪障碍，或DMDD，人群，见年度内科研究报告ZIAMH002786)。重要的是将青少年与BD和DMDD进行比较，因为特别是在DMDD被纳入DSM-5之前，易怒的儿童在社区中经常被诊断为BD，尽管没有躁狂病史。这种潜在的误诊很重要，因为与严重的慢性应激性相比，年轻人的BD是用副作用负担较高的药物治疗的。虽然将DMDD添加到DSM-5中可能降低了易怒儿童被误诊为BD的程度，但重要的是区分这些临床表现背后的大脑机制，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群体(成人BD、BD青少年、BD高危青少年)中，面部情绪处理一直是我们工作的主要重点。这是因为准确标记面部情绪的缺陷，以及面部情绪记忆缺陷，不仅存在于BD患者中，而且存在于有这种疾病风险的年轻人中。这些发现表明，面部情绪标记和记忆方面的缺陷是BD的潜在内表型。去年，我们发表了一篇论文，证明了当患有BD和DMDD的年轻人给情绪面孔贴上标签时，与易怒相关的神经机制在不同的诊断中是不同的。今年，我们进行了一项研究，其结果目前正在分析中。这项研究的目的是复制先前的工作，同时也研究不同群体的眼球跟踪模式。具体地说，受试者前一天在扫描仪中完成面部情绪标记范式，第二天在做眼球跟踪时完成。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，在给情绪面孔贴标签的同时，专注于眼睛区域的倾向减少了。DMDD组的结果是模棱两可的。我们的目标是复制我们之前的成像和眼球跟踪研究结果；检查眼球跟踪模式和神经活动之间的潜在联系；并确定患有DMDD的年轻人是否存在眼球跟踪缺陷。 我们对儿童双相情感障碍的研究一直很有成效。我们的成就包括证明，严重的慢性易怒并不是BD的儿科表现，而是患有BD的年轻人，就像患有这种疾病的成年人一样，经历可定义的躁狂发作。我们确定面部情绪标记和反应时变异性增加是BD潜在的可遗传生物标志物，并探索了调节它们的大脑机制。然而，我们已经决定终止这一项目，并将我们所有的资源投入到青少年慢性易激性的研究中(见年度报告ZIAMH002786)。原因是多方面的，包括易怒在年轻人中明显比BD更常见；关于易怒的研究明显缺乏；对易怒的循证治疗非常少。

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.