MRS and fMRI Studies of Neurobiological Factors in Panic Disorder

描述（由申请人提供）：总结：本研究的长期目标是更好地了解惊恐障碍易感性的神经生物学基础。大多数惊恐障碍的神经生物学模型提出了两种截然不同的脆弱性机制之一：1）代谢控制的“警报”系统功能障碍;或2）过敏的恐惧系统。应用脑能量代谢和质子磁共振波谱（1H-MRS）方法中的新概念，最近已经显示惊恐患者在神经激活期间比对照受试者积累更高水平的脑乳酸。乳酸盐是一种已知的致恐慌剂。与代谢“警报”模型一致，这可能代表在发病机制中具有关键作用的代谢异常。然而，乳酸反应升高可能是超敏恐惧系统和/或持续恐慌症状的结果，而不是具有潜在病因学意义的代谢异常。结合1H-MRS和fMRI方法，我们的目的是测试这两个帐户的升高脑乳酸反应的恐慌症的预测。我们将在3组中测量恐惧系统反应和脑乳酸反应：1）有症状的未治疗的惊恐患者，2）治疗的临床改善的惊恐患者，和3）对照受试者。对高度敏感的恐惧系统的预测将通过测量杏仁核对恐惧面孔的BOLD反应来测试。代谢模型的预测将通过测量1H-MRS视觉刺激过程中视皮层乳酸反应进行测试。初步数据表明，这两项措施将在未经治疗的患者异常升高。治疗患者的发现将有助于确定乳酸反应升高的潜在意义。如果接受治疗的患者的乳酸反应正常，则不太可能反映潜在和持久的代谢异常。然而，如果杏仁核反应随临床改善而正常化，但乳酸反应不正常，则乳酸反应升高可能与恐惧反应和持续的惊恐症状无关。这将支持一个潜在的代谢异常模型，该模型未被临床改善或正常化的恐惧反应所改变。R21机制的要求，因为我们的方法和概念代表了一种新的方法来研究惊恐障碍。相关性：关于恐慌症的生理原因有两种主要理论。该项目将测试每种理论对恐慌症患者恐惧反应和大脑代谢的预测，以更好地了解导致恐慌症的原因。

DESCRIPTION (provided by applicant): Summary: The long-term goal of this study is to better understand the neurobiological basis of susceptibility to panic disorder. Most neurobiological models of panic disorder propose one of two contrasting mechanisms of vulnerability: 1) dysfunction of a metabolically-governed "alarm" system; or 2) a hypersensitive fear system. Applying new concepts in brain energy metabolism and proton MR spectroscopy (1H-MRS) methods, panic patients have recently been shown to.accumulate higher levels of brain lactate during,neural activation than control subjects. Lactate is a known panicogen. Consistent with metabolic "alarm" models, this might represent a metabolic abnormality with a key role in pathogenesis. However, elevated lactate responses could be a consequence of a hypersensitive fear system and/or ongoing panic symptoms, rather than a metabolic abnormality with potential etiological significance. Combining 1H-MRS and fMRI methods, we aim to test the predictions of these two accounts of elevated brain lactate responses in panic disorder. We will measure fear system responses and brain lactate responses in 3 groups: 1) symptomatic, untreated panic patients, 2) treated, clinically improved panic patients, and 3) control subjects. The prediction of a hypersensitive fear system will be tested by measuring amygdala BOLD responses to fearful faces. The prediction of the metabolic model will be tested by measuring visual cortex lactate responses during visual stimulation with 1H-MRS. Preliminary data suggest both measures will be abnormally elevated in the untreated patients. Findings in the treated patients will help define the potential significance of the elevated lactate response. If the lactate response is normal in treated patients, it is unlikely to reflect an underlying and enduring metabolic abnormality. However, if amygdala responses normalize with clinical improvement but lactate responses do not, then elevated lactate responses may be independent of fear responses and ongoing panic symptoms. This would support the model of an underlying metabolic abnormality unaltered by clinical improvement or normalized fear responses. The R21 mechanism is requested because our methods and concepts represent a new approach to the study of panic disorder. Relevance: There are two leading theories about physical causes of panic disorder. This project will test predictions of each theory about fear responses and brain metabolism in panic patients in order to better understand what causes panic disorder.