Neumeister Alexander, Drevets Wayne C, Belfer Inna, Luckenbaugh David A, Henry Shannan, Bonne Omer, Herscovitch Peter, Goldman David, Charney Dennis S
Department of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.
Neuropsychopharmacology. 2006 Aug;31(8):1750-6. doi: 10.1038/sj.npp.1301010. Epub 2006 Jan 11.
Alterations in processing of emotionally salient information have been reported in individuals with major depressive disorder (MDD). Evidence suggests a role for noradrenaline in the regulation of a cortico-limbic-striatal circuit that has also been implicated in the pathophysiology of MDD. Herein, we studied the physiological consequences of a common coding polymorphism of the gene for the alpha(2C)-adrenoreceptor (AR) subtype--the deletion of four consecutive amino acids at codons 322-325 of the alpha2C-AR (alpha2CDel322-325-AR) in medication-free, remitted individuals with MDD (rMDD), and healthy control subjects. After injection of 10 mCi of H2(15)O, positron emission tomography (PET) measures of neural activity were acquired while subjects were viewing unmasked sad, happy, and fearful faces. The neural responses to sad facial expressions were increased in the amygdala and decreased in the left ventral striatum in rMDD patients relative to healthy control subjects. Furthermore, we report that rMDD carriers of one or two copies of the alpha2CDel322-325-AR exhibit greater amygdala as well as pregenual and subgenual anterior cingulate gyrus neuronal activity in response to sad faces than healthy alpha2CDel322-325-AR carriers and rMDD noncarriers. These results suggest that the alpha2CDel322-325-AR confers a change in brain function implicating this alpha2-AR subtype into the pathophysiology of MDD.
据报道，重度抑郁症（MDD）患者在处理情绪显著信息方面存在改变。有证据表明，去甲肾上腺素在调节皮质-边缘-纹状体回路中发挥作用，该回路也与MDD的病理生理学有关。在此，我们研究了α（2C）-肾上腺素能受体（AR）亚型基因常见编码多态性的生理后果——在无药物治疗且已缓解的MDD患者（rMDD）和健康对照受试者中，α2C-AR（α2CDel322-325-AR）在密码子322-325处连续四个氨基酸的缺失。在注射10毫居里的H2（15）O后，当受试者观看未遮挡的悲伤、快乐和恐惧面孔时，通过正电子发射断层扫描（PET）测量神经活动。相对于健康对照受试者，rMDD患者杏仁核中对悲伤面部表情的神经反应增强，而左腹侧纹状体中的反应减弱。此外，我们报告，与健康的α2CDel322-325-AR携带者和rMDD非携带者相比，携带一个或两个拷贝α2CDel322-325-AR的rMDD患者在面对悲伤面孔时，杏仁核以及膝前和膝下前扣带回神经元活动更强。这些结果表明，α2CDel322-325-AR导致脑功能改变，将这种α2-AR亚型纳入MDD的病理生理学。
