Neumeister Alexander, Bain Earle, Nugent Allison C, Carson Richard E, Bonne Omer, Luckenbaugh David A, Eckelman William, Herscovitch Peter, Charney Dennis S, Drevets Wayne C
National Institutes of Health, National Institute of Mental Health, Mood and Anxiety Disorders Program, Bethesda, Maryland 20892-2670, USA.
J Neurosci. 2004 Jan 21;24(3):589-91. doi: 10.1523/JNEUROSCI.4921-03.2004.
Recent animal models suggest that disturbances in serotonin type-1A receptor (5-HT(1A)R) function may contribute to chronic anxiety, although it is not clear at all whether such models constitute relevant models for panic disorder (PD) in humans. The selective 5-HT(1A)R radioligand [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (FCWAY) permits in vivo assessment of central 5-HT(1A)R binding using positron emission tomography (PET). We studied 16 unmedicated symptomatic outpatients with PD and 15 matched healthy controls. Seven patients had an additional diagnosis of a current major depressive episode, however PD was the primary diagnosis. A 120 min PET study of 5-HT(1A)R binding was acquired using a GE Advance scanner in three-dimensional mode. Using quantitative PET image analysis, regional values were obtained for [18F]-FCWAY volume of distribution (DV), corrected for plasma protein binding, and K1, the delivery rate of [18F]-FCWAY from plasma to tissue. MRI scanning was performed using a GE Signa Scanner (3.0 Tesla) to provide an anatomical framework for image analysis and partial volume correction of PET data. PD patients showed lower DV in the anterior cingulate (t = 4.3; p < 0.001), posterior cingulate (t = 4.1; p < 0.001), and raphe (t = 3.1; p = 0.004). Comparing patients with PD, patients with PD and comorbid depression, and healthy controls revealed that DVs did not differ between PD patients and PD patients with comorbid depression, whereas both patient groups differed significantly from controls. These results provide for the first time in vivo evidence for the involvement of 5-HT(1A)Rs in the pathophysiology of PD.
最近的动物模型表明，5-羟色胺1A受体（5-HT(1A)R）功能紊乱可能导致慢性焦虑，尽管目前尚不清楚此类模型是否能构成人类惊恐障碍（PD）的相关模型。选择性5-HT(1A)R放射性配体[18F]反式-4-氟-N-2-[4-(2-甲氧基苯基)哌嗪-1-基]乙基]-N-(2-吡啶基)环己烷甲酰胺（FCWAY）可通过正电子发射断层扫描（PET）对中枢5-HT(1A)R结合进行体内评估。我们研究了16名未用药的有症状的PD门诊患者和15名匹配的健康对照者。7名患者另外被诊断为当前患有重度抑郁发作，不过PD是主要诊断。使用GE Advance扫描仪以三维模式进行了一项为期120分钟的5-HT(1A)R结合PET研究。通过定量PET图像分析，获得了[18F]-FCWAY分布容积（DV）的区域值，该值已针对血浆蛋白结合进行校正，以及K1，即[18F]-FCWAY从血浆到组织的递送率。使用GE Signa扫描仪（3.0特斯拉）进行MRI扫描，为PET数据的图像分析和部分容积校正提供解剖学框架。PD患者在前扣带回（t = 4.3；p < 0.001）、后扣带回（t = 4.1；p < 0.001）和中缝核（t = 3.1；p = 0.004）中的DV较低。比较PD患者、合并抑郁症的PD患者和健康对照者发现，PD患者与合并抑郁症的PD患者之间的DV没有差异，而这两组患者与对照组均有显著差异。这些结果首次提供了5-HT(1A)R参与PD病理生理学的体内证据。
