Brain Lactate and Photic Stimulation in Panic Disorder

描述（由申请人提供）：恐慌症是一种潜在的致残焦虑症，影响1.5%至3.5%的人口。双胞胎研究表明，恐慌症有显著的遗传成分。然而，这种情况的潜在病理生理学尚不清楚。这项研究的长期目标是应用脑代谢的新概念来推进对恐慌症病因的理解。Klein（1993）试图从惊恐障碍的许多生理效应中区分潜在原因，提出了“窒息假警报”理论。在支持这一理论的观察中，一致的发现是恐慌症患者对各种代谢挑战的乳酸反应增加（Maddock 2001回顾）。脑乳酸最近被证明在有氧条件下的脑能量代谢中具有以前未被认识到的重要作用。最近使用质子磁共振波谱（1h - mrs）的研究表明，恐慌症患者脑实质对碱中毒的乳酸反应增加。了解这种作用的机制可能会揭示这种情况的潜在病理生理学。已经提出了几种机制，包括1)乳酸代谢内在动力学的干扰；2)脑血管收缩加剧引起的缺氧。这两种模型对恐慌症患者对感觉刺激的脑乳酸反应做出了截然不同的预测。本研究旨在否定这两种模式中的一种。用1H-MRS研究16例惊恐障碍患者和16例正常志愿者的脑乳酸对光刺激的反应。先前的研究表明，尽管有充足的氧气供应，光刺激会导致视觉皮层的乳酸积累。我们的初步研究证实了乳酸的增加。缺氧是恐慌症患者脑乳酸反应增加的必要条件，这一假设将被恐慌症患者对光刺激的乳酸反应增加的发现所证伪。相反，如果发现恐慌组和对照组之间的乳酸反应没有差异，那么恐慌患者乳酸代谢内在动力学受到干扰的假设将被证伪。这项研究的结果将限制可能的模型，可以解释这一现象，并指导未来的研究潜在的病理生理的恐慌症。

DESCRIPTION (provided by applicant): Panic disorder is a potentially disabling anxiety disorder affecting 1.5% to 3.5% of the population. Twin studies show that panic disorder has a significant heritable component. However, the underlying pathophysiology of this condition is not well understood. The long-term goal of this study is to apply new concepts of brain metabolism to advance understanding of the causes of panic disorder. In an attempt to distinguish underlying causes from the many physiological effects of panic disorder, Klein (1993) proposed the "suffocation false alarm" theory. Among the observations supporting this theory are the consistent findings of increased lactic acid responses to a variety of metabolic challenges in patients with panic disorder (reviewed in Maddock 2001). Brain lactate has recently been shown to have a previously unappreciated and significant role in brain energy metabolism under aerobic conditions. Recent studies using proton magnetic resonance spectroscopy (1 H-MRS) have shown increased lactate responses to alkalosis in the brain parenchyma of patients with panic disorder. Understanding the mechanism of this effect may shed light on the underlying pathophysiology of this condition. Several mechanisms have been proposed, including 1) a disturbance in the intrinsic dynamics of lactate metabolism; and 2) hypoxia due to increased cerebral vasoconstriction. These two models make distinctly different predictions about the brain lactate response to sensory stimulation in panic disorder. This study aims to reject one of these two models. The brain lactate response to photic stimulation will be studied with 1H-MRS in 16 patients with panic disorder and 16 matched normal volunteers. Prior studies show that photic stimulation leads to lactate accumulation in the visual cortex despite adequate oxygen supplies. Our pilot studies confirm this increase in lactate. The hypothesis that hypoxia is a necessary condition for the increased brain lactate responses in panic disorder would be falsified by a finding of increased lactate responses to photic stimulation in the panic patients. Conversely, the hypothesis that panic patients have a disturbance in the intrinsic dynamics of lactate metabolism would be falsified by finding no difference in the lactate response between the panic and control groups. The results of this study will constrain the possible models that can account for this phenomenon and guide future studies of the underlying pathophysiology of panic disorder.