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疾病，在整个过程中症状波动。这些波动表明，双相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腹侧前额叶皮层和皮层下的大脑区域调节的，这些区域形成了“前边缘网络”。“因此，我们假设双相情感障碍的症状是由这个网络中的功能障碍引起的。具体来说，功能成像（fMRI）研究表明，前边缘网络可能是过度激活双相情感障碍患者，从而产生这种情况的症状。此外，磁共振波谱（MRS）的研究表明，这种过度激活的结果，前边缘高代谢。此外，在躁狂症期间，MRS研究报告谷氨酸（Glx）浓度升高;过度的谷氨酸能神经传递可能是前边缘系统过度代谢和双相情感障碍激活的基础。双相情感障碍是渐进的，在病程早期发作频率增加，导致疾病的复发。与躁狂发作相关的兴奋性神经传递的反复增加可能导致兴奋性神经毒性，从而引发神经生理学变化，产生进行性情绪不稳定。目前尚不清楚是否有任何双相情感障碍的标准治疗方法可以防止这些变化。尽管如此，也许通过减少兴奋性多巴胺能神经传递，这些药物可能会纠正假设的过度前边缘系统激活和高代谢，并减少神经毒性的风险，从而防止疾病进展。需要在疾病显著进展之前对早期患者进行研究以做出这些决定。考虑到这些因素，本研究的目的是：1）使用1H-MRS来识别双相情感障碍在首次躁狂发作时的神经代谢异常，然后确定这些异常如何响应锂和奥氮平治疗而改变; 2）识别接受锂和奥氮平治疗时fMRI脑激活到认知探针（CRT-END）的相应变化; 3）证明局部脑激活变化与局部代谢变化相关。为了实现这些目标，我们将获得整合的神经代谢（MRS）和功能性神经解剖（fMRI）测量首次发作躁狂双相和健康受试者，以完善双相障碍的神经生理学模型（中心目标1）：确定急性躁狂症对两种机制不同的药物治疗反应的MRS和fMRI标记物（中心目标2）;并确定未来研究治疗反应的潜在预测因素（中心目标3）。