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

描述(由申请人提供)：双相情感障碍是一种动态状态，在其整个过程中都有症状波动。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受到大脑腹侧、前额叶、皮质和皮质下区域的调节，这些区域构成了“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。具体地说，功能成像(FMRI)研究表明，双相患者的前缘网络可能过度激活，从而产生这种情况的症状。此外，磁共振波谱(MRS)研究表明，这种过度激活是由于前缘过度代谢所致。此外，在躁狂期间，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双相情感障碍过度前缘代谢和激活的基础。双相情感障碍是进行性的，在病程早期随着发作频率的增加而增加，导致既定的、反复发作的疾病。与躁狂发作相关的兴奋性神经传递的反复增加可能会导致谷氨酸能神经毒性，从而启动神经生理学变化，从而产生进行性情绪不稳定。目前尚不清楚是否有任何治疗双相情感障碍的标准疗法可以阻止这些变化。然而，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前缘过度激活和高代谢，并降低神经毒性的风险，从而防止疾病的进展。在疾病显著进展之前，需要对早期病程患者进行研究，以做出这些决定。考虑到这些考虑，本研究的目标是：1)使用1H-MRS来确定双相情感障碍患者在首次躁狂发作时的神经代谢异常，然后确定这些异常对锂和奥氮平治疗的反应；2)确定接受锂和奥氮平治疗时脑功能磁共振成像对认知探针(CRT-END)的激活的相应变化；以及3)证明局部脑激活的变化与局部代谢变化有关。为了实现这些目标，我们将获取首发躁狂型双相情感障碍和健康受试者的综合神经代谢(MRS)和功能神经解剖学(FMRI)测量，以完善双相情感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不同药物的治疗反应的MRS和fMRI标志物(中心目标2)；并为未来研究确定潜在的治疗反应预测因素(中心目标3)。

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).