Increased 5-HT2A receptor binding in euthymic, medication-free patients recovered from depression:: A positron emission study with [11C] MDL 100,907
Increased 5-HT2A receptor binding in euthymic, medication-free patients recovered from depression:: A positron emission study with [11C] MDL 100,907
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DOI：
10.1176/appi.ajp.163.9.1580
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发表时间：
2006-09-01
影响因子：
17.7
通讯作者：
Grasby, Paul
中科院分区：
文献类型：
--
作者：
Bhagwagar, Zubin;Hinz, Rainer;Grasby, Paul
目的：先前的正电子发射断层扫描（PET）研究报告了未用药的抑郁症患者中5-羟色胺5-HT 2A受体结合增加，这些患者在功能障碍态度量表上得分较高。本研究的目的是在PET成像范例中使用高选择性5-HT 2A受体配体[C-11] MDL 100，907，以评估1）具有复发性抑郁症病史的正常胸腺受试者的5-HT 2A受体结合潜力和2）受体结合与功能失调态度量表评分之间的关系。方法：皮质5-HT 2A受体结合测定20个未经药物治疗，完全恢复的单相抑郁症患者和20个年龄和性别匹配的对照组。使用可逆血浆输入功能房室模型和小脑作为参考区域获得结合潜力的区域估计值，以估计脑组织中游离和非特异性结合的[C-11] MDL 100，907。结果如下：相对于对照组，恢复的抑郁症患者在额叶皮质（平均增加：19%）、顶叶皮质（平均增加：25%）和枕叶皮质（平均增加：19%）中表现出显著更高的5-HT 2A受体结合电位。5-HT 2A受体结合电位与患者和对照组的年龄呈负相关，与康复患者的功能障碍态度量表呈正相关。结论：这些发现应该被认为是初步的，但表明，恢复的受试者与复发性抑郁症的历史有升高的皮质5-HT 2A受体的结合潜力。增加5-HT 2A受体结合潜力与功能失调性态度量表评分增加的相关性支持了早期的工作，表明增加5-HT 2A受体的可用性是一组具有高水平功能失调性态度的抑郁症患者的特征。
Objective: A previous positron emission tomography (PET) study reported increased serotonin 5-HT2A receptor binding in unmedicated depressed patients with high scores on the Dysfunctional Attitudes Scale. The purpose of the present study was to use the highly selective 5-HT2A receptor ligand [C-11] MDL 100,907 in a PET imaging paradigm to assess 1) 5-HT2A receptor binding potential in euthymic subjects with a history of recurrent depression and 2) the relationship between receptor binding and scores on the Dysfunctional Attitudes Scale. Method: Cortical 5-HT2A receptor binding was measured in 20 unmedicated, fully recovered unipolar depressed patients and 20 age- and gender-matched comparison subjects. Regional estimates of binding potential were obtained using a reversible plasma input function compartmental model and the cerebellum as a reference region to estimate the free and non-specifically bound [C-11] MDL 100,907 in brain tissue. Results: Relative to the comparison subjects, the recovered depressed patients demonstrated significantly higher 5-HT2A receptor binding potential in the frontal cortex (mean increase: 19%),parietal cortex (mean increase: 25%), and occipital cortex (mean increase: 19%). 5-HT2A receptor binding potential correlated negatively with age in both patients and comparison subjects and positively with the Dysfunctional Attitudes Scale in the recovered patients. Conclusions: These findings should be considered preliminary but suggest that recovered subjects with a history of recurrent major depression have elevated binding potential of cortical 5-HT2A receptors. The correlation of increased 5-HT2A receptor binding potential with increased scores on Dysfunctional Attitudes Scale supports earlier work suggesting that increased 5-HT2A receptor availability characterizes a group of depressed patients with high levels of dysfunctional attitudes.