Brain Lactate and Photic Stimulation in Panic Disorder

描述（由申请人提供）：惊恐障碍是一种潜在的致残性焦虑障碍，影响1.5%至3.5%的人口。双胞胎研究表明，恐慌症有一个重要的遗传成分。然而，这种疾病的潜在病理生理学尚未得到很好的理解。这项研究的长期目标是应用大脑代谢的新概念来促进对恐慌症原因的理解。为了从恐慌症的许多生理影响中区分出潜在的原因，Klein（1993）提出了“窒息误报”理论。在支持这一理论的观察结果中，有一致的发现，即惊恐障碍患者对各种代谢挑战的乳酸反应增加（综述见Maddock 2001）。脑乳酸最近被证明在有氧条件下对脑能量代谢具有以前未被认识的重要作用。最近使用质子磁共振波谱（1H-MRS）的研究表明，惊恐障碍患者的脑实质中乳酸反应增加。了解这种影响的机制可能会揭示这种情况下的潜在病理生理学。已经提出了几种机制，包括1）乳酸代谢的内在动力学紊乱;和2）由于脑血管收缩增加导致的缺氧。这两个模型对惊恐障碍患者感觉刺激引起的脑乳酸反应做出了截然不同的预测。本研究旨在拒绝这两种模式之一。本文应用~ 1H-MRS研究了16例惊恐障碍患者和16例正常志愿者的光刺激脑乳酸反应。先前的研究表明，光刺激导致乳酸积累在视觉皮层，尽管有足够的氧气供应。我们的初步研究证实了乳酸盐的增加。惊恐障碍患者对光刺激的乳酸反应增加，这一发现推翻了低氧是惊恐障碍患者脑乳酸反应增加的必要条件的假设。相反，恐慌患者乳酸代谢的内在动力学紊乱的假设将被证明是错误的，因为恐慌组和对照组之间的乳酸反应没有差异。这项研究的结果将限制可能的模型，可以解释这种现象，并指导未来的研究惊恐障碍的基础病理生理学。

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.