杏仁核反应性中的基因型过度诊断：社交焦虑障碍中的情感加工
Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder.
作者信息
Furmark Tomas, Henningsson Susanne, Appel Lieuwe, Ahs Fredrik, Linnman Clas, Pissiota Anna, Faria Vanda, Oreland Lars, Bani Massimo, Pich Emilio Merlo, Eriksson Elias, Fredrikson Mats
机构信息
Department of Psychology, Uppsala University, Uppsala, Sweden.
出版信息
J Psychiatry Neurosci. 2009 Jan;34(1):30-40.
BACKGROUND
Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)-related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls.
METHODS
We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms.
RESULTS
Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles.
LIMITATIONS
Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrollment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli.
CONCLUSION
Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT-related genes into account.
背景
尽管杏仁核被认为是产生负面情绪的关键脑区，但神经影像学研究并不总是显示焦虑症患者的杏仁核对厌恶性刺激有增强的反应。血清素（5-HT）相关基因可能导致杏仁核反应性的个体差异。5-HT转运体基因连锁多态性区域（5-HTTLPR）的短（s）等位基因和色氨酸羟化酶-2（TPH2）基因中G-703T多态性的T变体，此前已被证明与健康对照者杏仁核对负面面孔的反应过度有关。我们研究了这些多态性对社交焦虑障碍（SAD）患者与健康对照者杏仁核对愤怒面孔反应性的影响。
方法
我们使用15O标记水的正电子发射断层扫描技术，评估34名SAD患者和18名对照者的局部脑血流，这些受试者以平衡顺序观看愤怒和中性面孔的照片。我们对所有参与者进行了5-HTTLPR和TPH2多态性的基因分型。
结果
与中性面孔相比，SAD患者和对照者在看到愤怒面孔时左侧杏仁核激活增加。基因型而非诊断能够解释杏仁核反应性差异的很大一部分，s和/或T等位基因携带者的反应更为明显。
局限性
由于样本量小以及我们在入组前无法根据基因型匹配参与者，我们的分析受到了限制。此外，我们研究中未使用的其他成像技术可能会揭示情绪刺激的额外影响。
结论
杏仁核对愤怒面孔的反应性与血清素能多态性的关系比与SAD的诊断更为密切。在比较患者组和对照组杏仁核兴奋性的情绪激活研究中，考虑5-HT相关基因的变异可能会有所帮助。
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