MRS INVESTIGATION OF LACTATE INDUCED PANIC

将使用1H磁共振波谱（MRS）测量乳酸盐 对静脉输注0.5 M乳酸钠的反应变化， 惊恐障碍和对照组。从这获得的信息 研究将促进我们对负责的机制的理解 乳酸盐引起的恐慌，并将其与恐慌的神经生物学联系起来。 乳酸盐输注是一种既定的方法， 自发性恐慌发作的生理反应特征， 易受影响的个体。这种乳酸反应性是一种敏感的， 对于经历恐慌的个体，但对于其他个体， 精神病人群或正常对照。虽然它是世界上 在生物精神病学中重复的发现， 乳酸盐引起的恐慌还未确定 直接测定脑池液中乳酸的增加 猴子静脉输注乳酸盐表明，脑乳酸盐可能 也增加。因此，增加大脑乳酸的具体效果， 长期提出但从未证明的间接影响， 外围机制，可能是恐慌产生的原因。 有大量文献表明，代谢异常和 呼吸失调可能会产生更大的上升和下降 惊恐患者对乳酸的反应性脑乳酸清除 输液我们已经证明了利用质子磁 共振波谱（1H MRS）检测全脑乳酸增加 在大鼠乳酸输注期间，定位1H MRS以检测增加的 正常人颞顶叶区的乳酸水平。试点 研究表明，对乳酸产生恐慌的受试者 显示出脑乳酸盐的更大增加和 与对照组相比输注。不恐慌的药物恐慌患者 在对乳酸盐响应中，出现中间脑乳酸盐升高 更像是控制。 在这项研究中，25名正常对照受试者和45名未服药的，积极 在乳酸期间，将通过1H MRS对症状性惊恐受试者进行评价 输液我们将专门测试假设，1）大脑乳酸 乳酸盐输注期间增加，2）恐慌受试者在反应中恐慌 乳酸输注的经验更大的上升，脑乳酸和延迟 与对照组相比，输注后脑乳酸清除率，3） 脑乳酸的过度升高和延迟清除呈负相关 但当潮气末pCO2 效果部分消失，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 尽管呼吸正常，但重复输注期间增加。 额外 试点研究将使用化学位移成像技术来评估 乳酸盐输注期间脑乳酸盐的解剖分布， 评估乳酸盐输注和自愿的联合作用 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.