Lanzenberger Rupert R, Mitterhauser Markus, Spindelegger Christoph, Wadsak Wolfgang, Klein Nikolas, Mien Leonhard-Key, Holik Alexander, Attarbaschi Trawat, Mossaheb Nilufar, Sacher Julia, Geiss-Granadia Thomas, Kletter Kurt, Kasper Siegfried, Tauscher Johannes
Department of General Psychiatry, Medical University of Vienna, Vienna, Austria.
Biol Psychiatry. 2007 May 1;61(9):1081-9. doi: 10.1016/j.biopsych.2006.05.022. Epub 2006 Sep 18.
Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD).
Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed.
We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030).
The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders.
对5-羟色胺1A（5-HT1A）基因敲除小鼠的研究结果以及先前对人类进行的正电子发射断层扫描（PET）研究表明，5-HT1A受体在正常状态焦虑以及某些焦虑症中发挥作用。本研究的目的是调查社交焦虑障碍（SAD）中5-HT1A受体结合潜能（BP）。
使用PET和[羰基-11C]WAY-100635，我们将12名未接受药物治疗的男性SAD患者的同质组与18名健康对照者（HC）进行了比较。以所有区域BP值为因变量，年龄和四个放射化学变量为协变量进行多变量方差分析。
我们发现SAD患者的几个边缘和边缘旁区域的5-HT1A BP显著降低，但海马体中没有（p = 0.234）。5-HT1A结合的差异在杏仁核中最为显著（-21.4%；p = 0.003）。SAD患者在前扣带回皮质（p = 0.004）、脑岛（p = 0.003）和中缝背核（p = 0.030）中的5-HT1A BP也降低了20%以上。
SAD患者杏仁核和内侧额叶区域较低的5-HT1A结合与以下几点一致：1）5-HT1A基因敲除小鼠焦虑升高的临床前研究结果；2）先前对健康志愿者进行的PET研究表明5-HT1A BP与状态焦虑呈负相关；3）另一项对惊恐障碍患者进行的人类PET研究表明5-HT1A结合减少，从而证实了5-HT1A受体作为人类焦虑症治疗靶点的潜在有效性。
