Brain Circuitry Analysis in Bipolar Disorder

项目摘要/摘要 双相情感障碍(BD)是一种情绪障碍，患者经历躁狂症或轻躁狂症，在 严重的抑郁症发作。即使目前所有可用的治疗方法，高复发率到躁狂和/ 或者，抑郁状态在整个疾病过程中持续存在。归根结底，早发性和慢性化 疾病导致BD成为年轻人的一种主要慢性疾病，也是全球残疾的主要原因。 来自这一提议的调查者的新数据，并得到文献的支持，表明 脑回路异常在BD的病理生理机制中起着重要作用。然而，全面理解 与BD相关的特定神经网络仍然是必要的。这个项目旨在描述大脑回路的特征。 以深入了解疾病的病因，可能有助于诊断和发展 新的治疗方法，包括手术干预，如脑深部刺激(DBS)。 这项拟议的研究将使用磁共振扩散加权成像来研究白质(WM)通路 三组受试者的气管造影术(DWT)：治疗-难治性BD(REF-BD)，治疗-有效BD (RSP-BD)和健康对照组(HC)。总体方法将建立在由进行的初步数据的基础上 研究人员发现，BD受试者和HCS患者之间的大脑连接存在差异，因为 在REF-BD和RSP-BD受试者之间也是如此。这些发现表明，特定的神经网络可能 且BD受试者之间表型差异可在DWT上识别。理解 而更全面地描绘这些途径将有助于揭示BD和BD的解剖基础 可以方便患者的诊断和指导治疗策略。 将利用研究小组独特的、分专业的专业知识来实现三个具体目标：1)使用 患者特异性神经成像(DWT)进一步描述BD患者大脑网络的WM解剖 与HCS相比。这将建立在使用高质量数据仓库数据集的试点数据、大样本大小和 控制精神活性药物。这些发现将提高我们对复杂的大脑回路的理解 参与BD；2)BD的相关临床特征(使用精神病学、眼球跟踪和神经心理学 评估)到DWT数据。结果可能识别BD表型的不同连接性生物标记物，可能 帮助患者诊断和治疗；以及3)探索刺激对累及的西医肌束的影响，使用 计算机建模和离散小波变换，以探讨DBS作为未来治疗BD患者的潜在方法。

PROJECT SUMMARY/ABSTRACT Bipolar disorder (BD) is a mood disorder in which patients experience mania or hypomania that cycles between episodes of major depression. Even with all currently available therapies, high rates of relapse into manic and/ or depressive states persist throughout the course of the disease. Ultimately, the early onset and chronicity of illness cause BD to be a major chronic disorder of young people and a leading cause of disability worldwide. Emerging data from the investigators of this proposal, which are supported by the literature, suggest that abnormal brain circuitry plays a role in the pathophysiology BD. However, a comprehensive understanding of the specific neural networks associated with BD is still needed. This project aims to characterize brain circuitry in BD subjects to gain insight into the etiology of the disorder, possibly aiding in diagnosis and in the development of new therapies, including surgical interventions such as deep brain stimulation (DBS). The proposed study will investigate white matter (WM) pathways using MR diffusion-weighted imaging based tractography (DWT) in three groups of subjects: Treatment-Refractory BD (REF-BD), Treatment-Responsive BD (RSP-BD), and Healthy Controls (HC). The overall approach will build upon the preliminary data conducted by the investigators, which found that connectivity differences in the brain exist between BD subjects and HCs, as well as between REF-BD and RSP-BD subjects. These findings indicate that specific neural networks may underlie BD, and that phenotypic differences between BD subjects may be identifiable on DWT. Understanding and delineating these pathways more comprehensively will shed light on the anatomical substrate of BD and may facilitate patient diagnosis and guide treatment strategies. The unique, subspecialty expertise of the study team will be employed to carry out three specific aims: 1) Use patient-specific neuroimaging (DWT) to further describe the WM anatomy of brain networks in BD subjects compared to HCs. This will build upon the pilot data using high quality DW datasets, a large sample size, and controlling for psychoactive medications. Findings will improve our understanding of the complex brain circuitry involved in BD; 2) Correlate clinical features of BD (using psychiatric, eye-tracking, and neuropsychological assessments) to DWT data. Results may identify distinct connectivity biomarkers for BD phenotypes, possibly aiding in patient diagnosis and treatment; and 3) Explore the effects of stimulation on implicated WM tracts, using computer modeling and DWT, to investigate DBS as a potential therapy for BD patients in the future.