Altered serotonin 1A binding in major depression: A [carbonyl-C-11]WAY100635 positron emission tomography study
Altered serotonin 1A binding in major depression: A [carbonyl-C-11]WAY100635 positron emission tomography study
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DOI：
10.1016/j.biopsych.2005.06.016
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发表时间：
2006-01-15
影响因子：
10.6
通讯作者：
Mann, JJ
中科院分区：
文献类型：
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作者：
Parsey, RV;Oquendo, MA;Mann, JJ
背景：5-羟色胺1A受体(5-HT1A)参与了抑郁症(MDD)的病理生理过程和选择性5-羟色胺再摄取抑制剂(SSRI)的作用。SSRI使5-HT1A脱敏，并下调5-HTT转运体(5-HTT)，后者在SSPI停药后持续数周。MDD患者更有可能是启动子多态的功能性5-HT1AG(-1019)等位基因的纯合子，并且推测其5-HT1A值高于健康志愿者(对照组)。方法：采用正电子发射断层扫描技术，对28例无药物治疗的MDD患者和43例对照组的5-HT1A结合潜能(BP)进行基因分型和测定。结果：对照组和MDD对照组的血压无显著差异(p=.235)。在所有地区，与对照组、抗抑郁药(AN)MDD受试者和患有AE的受试者相比，血压有差异(p=.013)。事后测试显示，与对照组(p=.008)和脑梗塞(p=.007)相比，AN组的BP更高。MDD患者GG基因高表达(p=0.059)，血压随G等位基因增加而升高。结论：AN患者的5-HT1a水平高于对照组和AE患者，提示抑郁症模型可能与G等位基因的高表达导致终末野5-HT1a释放减少有关。AE似乎对5-HT1A有长期影响
Background: Serotonin 1A receptors (5-HT1A) are implicated in the pathophysiology of major depressive disorder (MDD) and in the action of selective serotonin reuptake inhibitors (SSRI). SSRI desensitize 5-HT1A and down-regulate 5-HT transporters (5-HTT) with the latter persisting for weeks after discontinuation of SSPI. MDD subjects are more likely to be homozygous for the functional 5-HT1A G(-1019) allele of the promoter polymorphism and are postulated to have higher 5-HT1A than healthy volunteers (controls). We measure 5-HT1A in MDD, assess the effects of antidepressant exposure (AE), and examine the role of the C(-1019)G polymorphism.Methods: Genotyped and determined 5-HT1A binding potential (BP) by positron emission tomography (PET) using [carbonyl-C-11]-WAY-100635 in 28 medication-free MDD subjects during a current major depressive episode and 43 controls.Results: No difference in BP between controls and MDD subjects (p = .235). There was a difference in BP comparing the controls, antidepressant naive (AN) MDD subjects, and subjects with AE across all regions (p = .013). Post hoc testing reveals higher BP in AN compared to controls (p = .008) and to AE (p = .007). The GG genotype is overrpresented in MDD subjects (p = .059), and BP appears higher with the G allele.Conclusions: AN have higher 5-HT1A than controls and AE suggesting a model of depression characterized by an over expression of autoinhibitory somatodendritic 5-HT1A receptors, perhaps due to the higher expressing G allele, that may result in reduced terminal field 5-HT release. AE appears to have long-term effects on 5-HT1A