BRAIN METABOLISM AND TREATMENT OUTCOME IN PANIC DISORDER

恐慌症是最常见的精神疾病之一，在女性中尤为普遍。与恐慌症相关的发病率和死亡率都很高。尽管药物或认知行为疗法（CBT）有效治疗，但停止治疗后大约60%的复发率表明，恐慌症是一种受影响个体亚群的慢性疾病。治疗后的复发率似乎也受到治疗持续时间的影响，因为较长的药物治疗减少了在无药物治疗时随后复发的风险。迄今为止，我们的研究表明，患有恐慌症的个体存在脑代谢异常，表现为应对挑战（如乳酸输液或过度通气）时乳酸水平异常升高，这似乎具有特征特异性成分。也有证据表明，脑乳酸反应的异常程度随着治疗时间的延长而降低。本研究的目的是应用最新发展的动态代谢成像技术，蛋白质回波-平面光谱成像（PEPSI），测量乳酸输注后脑代谢变化，以便更好地了解治疗期间和停药后恐慌症、治疗反应和复发的神经病理机制。有症状、无介质的恐慌受试者（n=80）和健康对照（n=32）将在标准乳酸输注期间用百事可乐进行研究，然后在恐慌受试者随机分组后的12周再次接受CBT （n=40）或氟伏沙明（n=40）治疗。恐慌受试者将在持续治疗的1年乳酸回输期间重新研究，然后在停止治疗后进行1年的临床随访。对治疗不知情的临床评分员将负责对临床状况进行独立评估。假设在药物治疗期间持续的脑代谢异常，而不是CBT治疗，可以预测治疗过程和停药后复发的易感性。将尝试将治疗无应答者重新分配到相反治疗组，并重新研究这些个体（未作为相反治疗组的额外受试者），以便更好地了解治疗失败的机制。

Panic disorder is among the most common psychiatric disorders and is particularly prevalent among women. There is significant morbidity and mortality associated with panic disorder. Although effectively treated with medication or cognitive-behavioral therapy (CBT), an approximately 60 percent relapse rate after treatment discontinuation suggests that panic disorder is a chronic illness for a subpopulation of affected individuals. Relapse rates off treatment also appear to be influenced by treatment duration as longer treatment with medication reduces the risk for subsequent relapse when medication-free. Our studies to date suggest that individuals with panic disorder have brain metabolic abnormalities, manifested as abnormal lactate elevations in response to challenges, such as lactate infusion or hyperventilation, that appear to have a trait-specific component. There also is evidence that the magnitude of abnormal brain lactate response decreases in relationship to duration of treatment. The goal of this research is to apply a recently developed dynamic, metabolic imaging technique, protein echo- planar spectroscopic imaging (PEPSI), to measure brain metabolic changes in response to lactate infusion in order to better understand neuropathological mechanisms underlying panic disorder, treatment response and relapse both during treatment and after treatment discontinuation. Symptomatic, mediation-free panic subjects (n=80) and healthy controls (n=32) will be studied with PEPSI during a standard lactate infusion, and then again at 12 weeks following randomization of the panic subjects into treatment with CBT (n=40) or fluvoxamine (n=40). Panic subjects will be restudied during lactate reinfusion at 1 year while in ongoing treatment and then followed clinically for 1 year after discontinuation of treatment. A clinical rater blinded to treatment will be responsible for independent assessment of clinical status. It is hypothesized that persistence of brain metabolic abnormalities during medication treatment, but not CBT treatment, is predictive of treatment course and vulnerability to relapse following treatment discontinuation. An attempt will be made to reassign treatment nonresponders to the opposite treatment arm and restudy those individuals (not included as additional subjects in the opposite treatment arm), in order to better understand mechanisms underlying treatment failure.