Ultra High Field Strength MRI and MRS Study of Bipolar Disorder in Adolescents

项目总结/摘要：双相情感障碍（BD）是一种常见的严重医学疾病，影响 大约2%的人，通常在青春期发展。它给受影响的个人带来痛苦 以及在情感、社交、学业和工作方面的困难。它会导致终身的风险， 急性情绪发作，药物滥用和其他医学疾病（例如心脏病，糖尿病），以及早期 这一发病率及其自杀风险导致的死亡率是精神疾病中最高的。自杀是一种 青少年的死亡原因; BD是一个主要的风险因素。早期发现和治疗至关重要， 未经治疗的发作会使病程和预后恶化。我们在青少年BD患者中的研究结果显示， 杏仁核（AMY）是大脑中处理情绪的核心区域，其他研究小组也复制了这一结果 并且是BD的少数潜在早期标记之一。然后，我们展示了AMY体积之间的关联 减少和AMY活动过度。结合死后研究证据，这表明 BD中兴奋性神经递质谷氨酸（Glu）的神经毒性过度，可能对 对AMY结构和功能的影响。数据还支持AMY结构和功能的有益作用， 稳定情绪的药物，降低血糖水平。以前的研究主要是AMY作为一个 单一结构;然而，核具有不同的连接性和功能，并且特定的核越来越多地 与BD有关。因此，鉴定BD中涉及的特定核是重要的，因为核，其 连接的结构及其功能可能是检测，治疗和预防的特定目标。 BD.测量Glu和其他神经化学物质可以提供特定的分子靶点。先前 磁共振成像（MRI）和磁共振波谱（MRS）方法在较低的磁场强度， 不允许对特定AMY核进行形态学研究以及与Glu功能的关系。耶鲁 磁共振研究中心拥有Juchem、Mason和Rothman博士的专业知识，可执行7 T AMY MRI/MRS在体内用于AMY核的前所未有的结构成像和AMY Glu水平的测量， BD，以创新的方法提供高图像分辨率，灵敏度和光谱分辨率。我们 Berretta博士（哈佛大学）和Fudge博士（罗切斯特大学）是国际领先的 人类和非人类灵长类AMY解剖学和神经化学专家。在试点工作中，我们的团队 成功证明了在7特斯拉（7 T）下描绘AMY核和测量AMY Glu水平的能力。因此，在本发明中， 我们已经组建了一个非常独特和熟练的团队来完成急需的研究，这是第一个 它的种类。它有可能为BD的神经发育病理生理学提供新的见解， 确定AMY的形态学和分子靶点，以便早期检测、干预和预防。 这项研究可能会产生广泛的影响，因为它可以在7 T建立新的方法， BD和其他精神疾病研究的基准值。

PROJECT SUMMARY/ABSTRACT: Bipolar Disorder (BD) is a common, serious medical disorder, affecting about 2% of individuals, which typically develops in adolescence. It causes suffering for affected individuals and their families, and difficulties in emotional, social, school and work function. It leads to lifelong risk for acute mood episodes, substance abuse and other medical illnesses (e.g. heart disease, diabetes), and early mortality owing to this morbidity and its suicide risk, the highest of psychiatric disorders. Suicide is a leading cause of death in adolescents; BD is a major risk factor. Early detection and treatment are critical, as earlier, untreated episodes worsen course and prognosis. Our findings in adolescents with BD of volume decreases in the amygdala (AMY), a brain region central to emotion processing, was replicated by other research groups and is one of the few potential early markers for BD. We then showed associations between AMY volume decreases and AMY activity excesses. Together with postmortem study evidence, this suggests early neurotoxic excesses in BD in the excitatory neurotransmitter glutamate (Glu) that could have detrimental effects on AMY structure and function. Data also support salutary effects on AMY structure and function of mood stabilizing medications that decrease Glu levels. Previous studies have primarily been of the AMY as a unitary structure; however, nuclei have different connectivity and functions and specific nuclei are increasingly implicated in BD. Identification of specific nuclei involved in BD is therefore important as the nuclei, their connected structures and their functions could be specific targets for detection, treatment and prevention of BD. Measurement of Glu and other neurochemicals could provide specific molecular targets. Previous magnetic resonance imaging (MRI) and MR spectroscopy (MRS) methods at lower magnetic field strengths did not permit morphological study of specific AMY nuclei and the relationship to Glu functioning. The Yale Magnetic Resonance Research Center has the expertise of Drs. Juchem, Mason and Rothman to perform 7T AMY MRI/MRS in vivo for unprecedented structural imaging of AMY nuclei and measures of AMY Glu levels in BD, with innovative methods to provide high image resolution, sensitivity and spectral resolution. Our collaborators Drs. Berretta (Harvard University) and Fudge (University of Rochester) are international leading experts in AMY anatomy and neurochemistry in humans and non-human primates. In pilot work, our team successfully demonstrated ability to delineate AMY nuclei at 7 Tesla (7T) and measure AMY Glu levels. Thus, we have assembled a highly unique and skilled team to accomplish critically needed research that is the first of its kind. It has potential to provide novel insights into the neurodevelopmental pathophysiology of BD, identifying specific AMY morphological and molecular targets for early detection, intervention and prevention. The study could have broad high impact, as it could establish new methodological approaches at 7T and benchmark values for studies in BD and in other psychiatric disorders.