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

青少年双相情感障碍的超高场强 MRI 和 MRS 研究

基本信息

批准号：
9341381
负责人：
HILARY Patricia BLUMBERG
金额：
$ 20.94万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9341381
关键词：
Acute Adolescence Adolescent Affect Amygdaloid structure Anatomy Autopsy Benchmarking Bipolar Disorder Brain Brain Stem Brain region Cause of Death Cell Nucleus Chemicals Chemistry Circadian Rhythms Cognitive Communities Data Desire for food Detection Development Diabetes Mellitus Disease Early Diagnosis Early Intervention Early treatment Effectiveness Emotional Emotions Family Functional disorder Future Glutamates Glutamine Heart Diseases Hippocampus (Brain)Hormonal Human Hypothalamic structure Image Individual International Intervention Lateral Lead Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manic Measurement Measures Medial Dorsal Nucleus Medical Mental Depression Mental disorders Methodology Methods Molecular Target Moods Morbidity - disease rate Morphology Motivation Neurons Neurotransmitters Pharmaceutical Preparations Positioning Attribute Prefrontal Cortex Prevention Prevention strategy Reporting Research Research Personnel Resolution Risk Risk Factors Role Schools Sensory Severities Sleep Stimulus Structure Study of magnetics Substance abuse problem Suicide Symptoms Thalamic structure Time Universities Visceral Work association cortex behavioral response brain circuitry emotion regulation field study high resolution imaging imaging study improved in vivo in vivo imaging innovation insight magnetic field mood symptom mortality neurochemistry neurotoxic nonhuman primate novel outcome forecast social spectroscopic imaging suicidal risk transmission process

项目摘要

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.

项目摘要/摘要：双相情感障碍 (BD) 是一种常见的严重疾病，影响约2%的人发生这种情况，通常发生在青春期。它给受影响的个人带来痛苦及其家人，以及情感、社交、学业和工作功能方面的困难。它会导致终生风险急性情绪发作、药物滥用和其他疾病（例如心脏病、糖尿病）以及早期这种发病率及其自杀风险导致的死亡率是精神疾病中最高的。自杀是一个主导青少年死亡原因； BD 是一个主要的危险因素。早期发现和治疗至关重要，因为早期未经治疗的发作会恶化病程和预后。我们对患有 BD 的青少年的研究结果显示，杏仁核（AMY）是情绪处理的核心大脑区域，已被其他研究小组复制是 BD 的少数潜在早期标志物之一。然后我们展示了 AMY 体积之间的关联减少和 AMY 活动过度。结合尸检研究证据，这表明早期 BD 中兴奋性神经递质谷氨酸 (Glu) 的神经毒性过量，可能会产生有害的影响对 AMY 结构和功能的影响。数据还支持 AMY 结构和功能的有益影响降低谷氨酸水平的情绪稳定药物。之前的研究主要是将 AMY 作为单一结构；然而，原子核具有不同的连接性和功能，并且特定的原子核越来越多与BD有关。因此，鉴定参与 BD 的特定核非常重要，因为核、它们的连接的结构及其功能可以成为检测、治疗和预防的具体目标 BD。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。以前的磁共振成像（MRI）和磁共振波谱（MRS）方法在较低磁场强度下确实不允许对特定 AMY 核及其与 Glu 功能的关系进行形态学研究。耶鲁大学磁共振研究中心拥有博士的专业知识。 Juchem、Mason 和 Rothman 将表演 7T AMY MRI/MRS 体内 AMY 核的前所未有的结构成像以及 AMY Glu 水平的测量 BD，以创新方法提供高图像分辨率、灵敏度和光谱分辨率。我们的合作者博士。 Berretta（哈佛大学）和Fudge（罗切斯特大学）国际领先 AMY 人类和非人类灵长类动物解剖学和神经化学专家。在试点工作中，我们的团队成功展示了在 7 特斯拉 (7T) 下描绘 AMY 核和测量 AMY Glu 水平的能力。因此，我们组建了一支高度独特且技术精湛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，确定特定的 AMY 形态和分子目标，以进行早期检测、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 7T 和 BD 和其他精神疾病研究的基准值。