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

基本信息

批准号：
9568251
负责人：
Ellen Leibenluft
金额：
$ 54.56万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
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/9568251
关键词：
Adolescent Adult Adverse effects Amish Annual Reports Attention Base of the Brain Behavioral Paradigm Biological Markers Bipolar Disorder Brain Child Childhood Chronic Clinical Clinical Markers Communities DNA Sequence Alteration DSM-V Development Diagnosis Disease Emotional Emotions Enrollment Evidence based treatment Eye Face Family First Degree Relative Functional Magnetic Resonance Imaging Future Genetic Materials Goals Heritability Image Impairment Intramural Research Label Manic Mediating Memory Moods Mutation Neurocognitive Paper Parents Patients Pattern Pharmaceutical Preparations Population Preventive Intervention Process Protocols documentation Public Health Publishing Punishment Reaction Time Recording of previous events Reporting Research Resources Rewards Risk Running Siblings Standardization Study Subject Symptoms Testing Time Work Youth behavior test childhood bipolar disorder design disorder risk emotional stimulus endophenotype experience indexing interest longitudinal course neural circuit neuromechanism neurophysiology outcome forecast phenomenological models prevent psychologic relating to nervous system response therapy development treatment response

项目摘要

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.

自从该项目开始以来，我们已经筛选了3000多个受试者为这项研究。我们已经招募了大约215名双相情感障碍（BD）青年，320名受试者患有BD，因为他们有父母或患有疾病的兄弟姐妹，还有120名BD成年人。今年，约有15名新主题被招募。今年，我们继续旨在确定儿童BD的大脑机制；比较BD的青年和成人的大脑功能，以便开始了解疾病随着时间的流逝如何发展；并将BD家庭风险的大脑功能与BD和低风险患者的大脑功能进行比较，以促进预防干预措施的最终发展。关于我们在介导BD的大脑机制方面的工作，其中大部分工作不仅包括将BD的青年与健康的青年进行比较，还将BD的青年与患有严重，慢性烦躁的严重烦恼的年轻人进行比较（所谓的破坏性情绪失调或DMDD，人口，人口，参见年度内部研究报告ZiamH002786）。重要的是将青年与BD和DMDD的年轻人进行比较，因为尤其是在DSM-5中纳入DMDD之前，易怒的孩子经常在社区中诊断为BD，尽管没有躁狂发作的病史。这种潜在的误诊很重要，因为与严重的慢性烦躁不良相比，青年人的BD受到高副作用负担的药物治疗。虽然将DMDD添加到DSM-5可能降低了易受易激儿童被误诊为具有BD的程度，但尽管诊断之间的差异可能与治疗方法相关，但很重要的是，要区分这些临床表现的脑机制很重要。在我们与躁郁症相关的群体（BD成年人，BD的年轻人，有BD风险的青年）中，面对情感处理一直是我们工作的主要重点。这是因为不仅存在于BD患者，而且还出现在患有这种疾病风险的青年中，不仅存在赤字准确地标记面部情绪以及面部情绪记忆中的缺陷。这些发现表明，面部情绪标记和记忆中的这种缺陷是BD的潜在内型型。去年，我们发表了一篇论文，该论文表明，当BD和DMDD的青年标记情感面孔时，与烦恼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，目前正在分析结果。这项研究旨在复制先前的工作，同时还研究各组之间的眼动追踪模式。具体来说，受试者有一天会在扫描仪中完成脸部范围的范式，第二天在进行眼睛跟踪时完成了范围。在先前发表的工作中，我们发现有BD的青年和有疾病风险的青年在标记情感面孔的同时，专注于眼睛区域的趋势下降。 DMDD组的结果是模棱两可的。我们的目标是复制我们以前的成像和眼动追踪发现。检查眼睛跟踪模式与神经活动之间的潜在关联；并确定DMDD的青年是否有吸引人的赤字。我们关于小儿躁郁症疾病的研究一直有效。我们的成就包括证明严重的慢性烦躁不良不是BD的儿科表现，而是BD的年轻人，例如患有疾病的成年人，经历了躁狂症的可确定情节。我们将面部情绪标记和反应时间的变异性增加为BD的潜在生物标志物，并探索了每个介导的大脑机制。但是，我们已决定终止该项目，并将所有资源投入到青年人的慢性易怒研究中（请参阅年度报告Ziamh002786）。其原因是多重的，包括在青年中比BD更为普遍的事实。关于易怒的研究很少。而且很少有基于证据的烦恼治疗方法。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Skating to where the puck will be: the importance of neuroimaging literacy in child psychiatry.

滑向冰球所在的位置：神经影像素养在儿童精神病学中的重要性。

DOI：
10.1097/chi.0b013e318185dab8
发表时间：
2008
期刊：
Journal of the American Academy of Child and Adolescent Psychiatry
影响因子：
13.3
作者：
Leibenluft,Ellen
通讯作者：
Leibenluft,Ellen

The ties that bind: maternal-infant interactions and the neural circuitry of postpartum depression.

联系的纽带：母婴互动和产后抑郁症的神经回路。

DOI：
10.1176/appi.ajp.2010.10081159
发表时间：
2010
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Leibenluft,Ellen;Yonkers,KimberlyA
通讯作者：
Yonkers,KimberlyA

Functional connectivity during masked and unmasked face emotion processing in bipolar disorder.

双相情感障碍中蒙面和未蒙面情绪处理过程中的功能连接。

DOI：
10.1016/j.pscychresns.2016.10.006
发表时间：
2016
期刊：
Psychiatry research. Neuroimaging
影响因子：
0
作者：
Tseng,Wan-Ling;Thomas,LauraA;Harkins,Elizabeth;Stoddard,Joel;ZarateJr,CarlosA;Pine,DanielS;Leibenluft,Ellen;Brotman,MelissaA
通讯作者：
Brotman,MelissaA

Pediatric bipolar disorder comes of age.