MRS INVESTIGATION OF LACTATE INDUCED PANIC

将使用~1H磁共振波谱(MRS)来测量乳酸 静脉输注0.5M乳酸钠后反应变化的比较 惊恐障碍和控制受试者。从本网站获得的信息 研究将促进我们对导致 乳酸盐引起的恐慌，并将其与恐慌的神经生物学联系起来。 乳酸输注是一种既定的方法，可以诱导心理和 自发性惊恐发作的生理反应特征 易感人群。这种乳酸反应是一种敏感的和 为经历恐慌的个人而不是其他人的特定标记 精神病患者或正常对照组。尽管它是世界上 生物精神病学中重复的发现，负责的机制 乳酸盐引起的恐慌仍未确定。 直接测定脑池液中乳酸的升高 在猴子体内静脉注射乳酸表明，脑乳酸可能 也增加了。因此，相反，增加大脑乳酸的具体影响 长期提出但从未表现出间接影响 外围机制，可能会导致恐慌的产生。 有大量文献表明新陈代谢异常和 呼吸失调可能会导致更大的上升和下降 惊恐患者对乳酸的反应中脑乳酸的清除 输液。我们已经证明了使用质子磁铁的可行性。 磁共振波谱(1H MRS)检测全脑乳酸升高 大鼠输注乳酸盐过程中及局部1H MRS检测升高 正常人顶叶-颞区乳酸含量。引航员 研究表明，惊慌失措的受试者对乳酸的反应会产生恐慌 显示出脑乳酸和延迟清除后更大的增加 输液与对照组的比较。服用药物的恐慌症患者不会惊慌 在对乳酸的反应中，中间脑乳酸似乎会上升 更像是控件。 在这项研究中，25名正常对照受试者和45名未服用药物的受试者积极 有症状的惊恐受试者将在乳酸盐期间进行1H MRS评估 输液。我们将专门测试假设：1)大脑乳酸盐 在乳酸输注过程中增加，2)惊慌失措的受试者 要经历更大的乳酸输注，大脑乳酸会有较大的上升和延迟 与对照组比较，输注后脑组织乳酸清除量 脑乳酸过度升高和清除延迟与此呈负相关 呼吸暂停，但呼气末二氧化碳分压时患者控制性差异仍然存在 效果是分散的，4)短期治疗后， 无症状的恐慌症患者将继续表现出过量的脑乳酸 在重复输液过程中增加，尽管呼吸正常。其他内容 试点研究将使用化学位移成像技术来评估 乳酸输注过程中脑组织乳酸的解剖分布 评估乳酸盐输注和自愿输注的联合效果 健康对照组的过度换气。

1H magnetic resonance spectroscopy (MRS) will be used to measure lactate changes in response to intravenous 0.5 M sodium lactate infusion comparing panic disorder and control subjects. Information obtained from this research will advance our understanding of mechanisms responsible for lactate-induced panic and relate this to the neurobiology of panic. Lactate infusion is an established method to elicit psychological and physiological response characteristic of a spontaneous panic attack in susceptible individuals. This lactate responsiveness is a sensitive and specific marker for individuals experiencing panic but not for other psychiatric populations or normal controls. Although it is one of the most replicated findings in biological psychiatry, the mechanism responsible for lactate-induced panic remains undetermined. Direct measurement of increased lactate in cisternal fluid during intravenous lactate infusion in monkeys suggests that brain lactate may also increase. Thus, specific effects of increasing brain lactate, instead of long proposed but never demonstrated indirect effects through peripheral mechanisms, could be responsible for the production of panic. There is a body of literature suggesting that metabolic abnormalities and respiratory dysregulation may produce greater rises and decreased clearance of brain lactate among panic patients in response to lactate infusion. We have demonstrated the feasibility of using proton magnetic resonance spectroscopy (1H MRS) to detect increased whole brain lactate during lactate infusion in rats and localized 1H MRS to detect increased lactate in the temporal-parietal region of normal human controls. Pilot studies suggest that panic subjects who panic in response to lactate demonstrate greater increases in brain lactate and delayed clearance post- infusion compared to controls. Medicated panic patients who do not panic in response to lactate appear to have intermediate brain lactate rises more resembling controls. In this study, 25 normal control subjects and 45 unmedicated, actively symptomatic panic subjects will be evaluated by 1H MRS during lactate infusion. We will specifically test hypotheses that 1) brain lactate increases during lactate infusion, 2) panic subjects who panic in response to lactate infusion experience greater rises in brain lactate and delayed clearance of brain lactate post-infusion compared to controls, 3) excessive rise and delayed clearance of brain lactate is inversely related to hypocapnea but patient-control differences remain when end-tidal pCO2 effects are partialled out, and 4) following short-term treatment, asymptomatic panic patients will continue to exhibit excess brain lactate increases during repeat infusion despite normal respiration. Additional pilot studies will use chemical-shift imaging techniques to assess anatomical distribution of brain lactate during lactate infusion and assess the combined effects of lactate infusion and voluntary hyperventilation in healthy controls.