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。 有显着的发病率和死亡率与惊恐障碍。 虽然有效地治疗药物或认知行为疗法（CBT），治疗停止后约60%的复发率表明，恐慌症是一种慢性疾病的一个亚群受影响的个人。停止治疗后的复发率似乎也受到治疗持续时间的影响，因为药物治疗时间较长可降低随后无药物治疗时复发的风险。 我们迄今为止的研究表明，惊恐障碍患者存在脑代谢异常，表现为对挑战的异常乳酸升高，如乳酸输注或过度通气，似乎具有特质特异性成分。也有证据表明，异常脑乳酸反应的幅度与治疗持续时间有关。 本研究的目的是应用最近开发的动态代谢成像技术，蛋白质回波平面光谱成像（PEPSI），以测量脑代谢变化，以更好地了解治疗期间和治疗停止后惊恐障碍，治疗反应和复发的神经病理学机制。 将在标准乳酸盐输注期间对有症状、无药物治疗的惊恐受试者（n=80）和健康对照（n=32）进行PEPSI研究，然后在惊恐受试者随机接受CBT（n=40）或氟伏沙明（n=40）治疗后12周再次进行研究。 恐慌受试者将在持续治疗的1年乳酸盐再输注期间重新研究，然后在停止治疗后进行1年临床随访。 对治疗设盲的临床评估者将负责独立评估临床状态。 假设药物治疗期间脑代谢异常的持续性，而不是CBT治疗，是治疗过程和治疗停止后复发的脆弱性的预测。 将尝试将治疗无应答者重新分配至相反治疗组，并重新研究这些个体（不作为额外受试者纳入相反治疗组），以更好地了解治疗失败的潜在机制。

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.