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

项目摘要/摘要：双相情感障碍(BD)是一种常见、严重的医学障碍，影响 大约2%的人，这通常发生在青春期。它会给受影响的个人带来痛苦 以及在情感、社会、学校和工作功能方面的困难。它会导致终生的风险 急性情绪发作、药物滥用和其他内科疾病(如心脏病、糖尿病)，以及早期 这一发病率造成的死亡率及其自杀风险是精神障碍中最高的。自杀是最重要的 青少年的死亡原因；BD是一个主要的危险因素。如前所述，及早发现和治疗至关重要， 未经治疗的发作会恶化病程和预后。我们在患有BD的青少年中的发现 其他研究小组也复制了杏仁核(AMY)，这是大脑中情绪处理的中心区域 是BD为数不多的潜在早期标志物之一。然后我们展示了艾米音量之间的联系 减少和艾米的过度活动。结合尸检证据，这表明早期 BD患者兴奋性神经递质谷氨酸(Glu)的神经毒性过量，可能对 对AMY结构和功能的影响。数据也支持了对AMY结构和功能的有益影响 降低谷氨酸水平的稳定情绪的药物。以前的研究主要是将艾米作为一种 结构单一；然而，核具有不同的连通性和功能，并且特定的核越来越多 与BD有牵连。因此，识别BD中涉及的特定核是重要的，因为它们的核、它们的 相连的结构及其功能可以成为检测、治疗和预防的特定目标 BD。对谷氨酸和其他神经化学物质的测量可以提供特定的分子靶点。上一首 在较低磁场强度下的磁共振成像(MRI)和磁共振波谱(MRS)方法 不允许对特定的AMY核及其与Glu功能的关系进行形态研究。耶鲁大学 磁共振研究中心拥有朱查姆、梅森和罗斯曼博士的专业知识来进行7T 体内AMY MRI/MRS对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。我们的 合作者贝雷塔博士(哈佛大学)和福吉博士(罗切斯特大学)是国际领先的 人类和非人类灵长类动物的艾米解剖学和神经化学专家。在试点工作中，我们团队 成功地展示了在7特斯拉(7T)上描绘AMY核并测量AMY Glu水平的能力。因此， 我们已经组建了一支非常独特和熟练的团队来完成急需的研究，这是第一个 它是一种。它有可能为BD的神经发育病理生理学提供新的见解， 识别特定的AMY形态和分子靶点，以便早期发现、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7T和7T建立新的方法学方法 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.