U of Cincinnati Bipolar Disorder Imaging & Treatment Research Center (BITREC)

辛辛那提大学双相情感障碍成像

• 批准号: 7637870
• 负责人: STEPHEN M STRAKOWSKI
• 金额: $ 192.93万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7637870
• 关键词: Cincinnati; Bipolar; Disorder; Imaging; Treatment

DESCRIPTION (provided by applicant): Bipolar disorder is a dynamic condition with symptomatic fluctuations throughout its course. These fluctuations suggest that bipolar neurophysiology involves dysfunction of brain networks that maintain emotional homeostasis. Human emotional behavior appears to be modulated by ventral prefrontal cortical and subcortical brain regions that form the 'anterior limbic network.' Consequently, we hypothesize that the symptoms of bipolar disorder arise from dysfunction within this network. Specifically, functional imaging (fMRI) studies suggest that the anterior limbic network may be over-activated in bipolar patients, thereby producing the symptoms of this condition. Additionally, magnetic resonance spectroscopy (MRS) studies suggest that this over-activation results from anterior limbic hypermetabolism. Moreover, during mania, MRS studies report elevated glutamate (Glx) concentrations; excessive glutamatergic neurotransmission may underlie the excessive anterior limbic metabolism and activation of bipolar disorder. Bipolar disorder is progressive with increasing episode frequency early in the illness course, leading to an established, recurrent illness. Repeated increases in excitatory neurotransmission associated with manic episodes may cause glutamatergic neurotoxicity, thereby initiating neurophysiologic changes that produce progressive emotional instability. It is not known whether any of the standard treatments for bipolar disorder prevent these changes. Nonetheless, perhaps by decreasing excitatory glutamatergic neurotransmission, these medications might correct the hypothesized excessive anterior limbic activation and hypermetabolism, and diminish the risk of neurotoxicity, thereby preventing disease progression. Studies of early course patients, prior to significant disease progression, are needed to make these determinations. With these consideration in mind, the goals of this study are: 1) To use 1H-MRS to identify neurometabolic abnormalities in bipolar disorder at the time of the first manic episode, and then determine how these abnormalities change in response to lithium and olanzapine treatment; 2) To identify corresponding changes in fMRI brain activation to a cognitive probe (CRT-END) while receiving lithium and olanzapine therapy; and 3) To demonstrate that regional brain activation changes are associated with regional metabolic changes. To accomplish these aims, we will acquire integrated neurometabolic (MRS) and functional neuroanatomic (fMRI) measurements in first-episode manic bipolar and healthy subjects in order to refine neurophysiological models of bipolar disorder (Center goal 1); to identify MRS and fMRI markers of treatment response of acute mania to two mechanistically different medications (Center goal 2); and to identify potential predictors of treatment response for future studies (Center goal 3).

描述（由申请人提供）：双相情感障碍是一种动态状况，整个过程中有症状波动。这些波动表明，双极神经生理学涉及维持情绪稳态的大脑网络功能障碍。人类的情绪行为似乎是由构成“前边缘网络”的腹侧前额叶皮质和皮质下脑区域调节的。因此，我们假设躁郁症的症状是该网络中功能障碍引起的。具体而言，功能成像（fMRI）研究表明，双极患者可能过度激活前边缘网络，从而产生这种情况的症状。另外，磁共振光谱（MRS）研究表明，这种过度激活是由前边缘超级代谢引起的。此外，在躁狂症期间，MRS研究报告说谷氨酸升高（GLX）浓度升高。过度的谷氨酸能神经传递可能是过度前边缘代谢和双相情感障碍的激活的基础。双相情感障碍是渐进的，随着发作频率在疾病病程的早期频率增加，导致了已建立的复发性疾病。与躁狂发作相关的兴奋性神经传递的重复增加可能会引起谷氨酸能神经毒性，从而启动神经生理学的变化，从而导致逐步的情绪不稳定。尚不清楚躁郁症的任何标准治疗方法是否阻止了这些变化。尽管如此，也许通过减少兴奋性谷氨酸能神经传递，这些药物可能会纠正假设的过度前边缘激活和超定代谢，并降低神经毒性的风险，从而防止疾病进展。需要在重大疾病进展之前对早期病例患者进行研究以做出这些决定。考虑到这些考虑，这项研究的目标是：1）在第一次躁狂发作时使用1H-MR来鉴定躁郁症中的神经代谢异常，然后确定这些异常对锂和奥氮平治疗的响应方式如何变化； 2）在接受锂和奥氮平治疗时，识别fMRI脑激活对认知探针（CRT末端）的相应变化； 3）证明区域大脑激活变化与区域代谢变化有关。为了实现这些目标，我们将获得综合的神经代谢（MRS）和功能性神经解剖学（FMRI）测量，以提高双相情感障碍的神经生理模型（中心目标1）；鉴定急性躁狂对两种机械上不同药物的治疗反应的MRS和FMRI标记（中心目标2）；并确定未来研究的治疗反应的潜在预测指标（中心目标3）。