Functional and neurochemical brain changes in first episode

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 波动提示双相神经生理学涉及大脑网络的功能障碍，维持 情绪动态平衡。人类的情绪行为似乎受到腹侧前额叶皮质的调节 以及皮质下形成“前边缘网络”的脑区。因此，我们假设 双相情感障碍的症状源于这个网络内的功能障碍。具体地说，功能成像 功能磁共振成像(FMRI)研究表明，双相情感障碍患者的前缘网络可能过度激活，从而 产生这种情况的症状的。此外，磁共振波谱(MRS)研究 提示这种过度激活是前缘过度代谢的结果。此外，在狂热期间，梅根夫人 研究报告谷氨酸(GLX)浓度升高；谷氨酸能神经传递过度可能 过度的前缘代谢和双相情感障碍的激活是其基础。 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 复发性疾病一种既定的、反复发作的疾病与躁狂症相关的兴奋性神经传递的反复增加 发作可能会导致谷氨酸能神经毒性，从而引发神经生理变化，从而产生 渐进性情绪不稳定。目前尚不清楚是否有任何治疗双相情感障碍的标准疗法 防止这些更改。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，从而防止疾病进展。关于早期课程的研究 在疾病显著进展之前，患者需要做出这些决定。 考虑到这些考虑，本研究的目标是：1)使用1H-MRS来识别 双相情感障碍患者首次躁狂发作时的神经代谢异常，然后确定 这些异常如何改变对锂和奥氮平治疗的反应；2)确定 接受锂和锂时认知探针(CRT-END)的fMRI脑激活的相应变化 奥氮平治疗；以及3)证明区域大脑激活的变化与 区域性代谢变化。为了实现这些目标，我们将获得整合的神经代谢(MRS) 和功能神经解剖学(FMRI)测量首发躁狂症双相情感障碍和健康受试者 为了完善双相情感障碍的神经生理学模型(中心目标1)；识别MRS和fMRI 急性躁狂症对两种不同药物治疗反应的标记物(中心目标2)； 并为未来的研究确定治疗反应的潜在预测因素(中心目标3)。

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).