Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder
Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder
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DOI：
10.1001/archpsyc.63.7.741
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发表时间：
2006-07-01
影响因子：
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通讯作者：
Drevets, Wayne C.
中科院分区：
文献类型：
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作者：
Cannon, Dara M.;Carson, Richard E.;Drevets, Wayne C.
内容：多种间接证据表明，中枢毒蕈碱胆碱能系统，尤其是2型毒蕈碱（M-2）受体参与了抑郁症和双相情感障碍的发病机制。目的：评估重度抑郁症或双相情感障碍患者抑郁症期间体内毒蕈碱2受体的结合潜力。设计：使用正电子发射断层扫描和[F-18]FP-TZTP，比较了未用药的重度抑郁症或双相情感障碍受试者与健康对照者的M-2受体结合情况（fluorodopa F 18 [3-（3-[3-fluoropropy] thio）-1，2，5-thiadiazol-4-yl]-1，2，5，6-tetrahydro-1-methylpyridine），一种选择性M-2受体放射性配体。目前抑郁症符合DSM-IV标准的未用药受试者（n=17）或双相情感障碍（n=16）和23名健康对照受试者。主要结果参数是[F-18] FP-TZTP分布体积，其与受体密度和亲和力的乘积成比例，在[F-18] FP-TZTP的情况下，已知对内源性乙酰胆碱浓度敏感。使用蒙哥马利-阿斯伯格抑郁和汉密尔顿焦虑量表评定的疾病严重程度与分布体积之间的关系也进行了评估。（F-55=3.4; P= 0.04），这种差异是由双相情感障碍与重性抑郁障碍和对照组相比，结合率显著降低所致。双相情感障碍受试者的平均M-2受体结合相对于健康对照组和重度抑郁障碍受试者均降低，其程度与抑郁症状相关。双相情感障碍组的减少可以通过M-2受体密度或亲和力的降低或内源性乙酰胆碱水平的升高来解释。据我们所知，这些数据提供了第一个直接证据，表明改变M-2受体功能有助于双相情感障碍的情绪失调。
Context: A variety of indirect evidence has implicated the central muscarinic-cholinergic system, and more specifically the type 2 muscarinic (M-2) receptor, in the pathogenesis of depressive symptoms arising in major depressive disorder and bipolar disorder.Objective: To assess the binding potential of muscarinic2 receptors in vivo during depression in subjects with major depressive disorder or bipolar disorder.Design: The M-2 receptor binding was compared between unmedicated subjects with major depressive disorder or bipolar disorder during depression vs healthy controls, using positron emission tomography and [F-18]FP-TZTP (fluorodopa F 18 [3-(3-[3-fluoroproply] thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine), a selective M-2 receptor radioligand.Setting: Outpatients at the National Institutes of Health.Participants: Unmedicated subjects with current depression meeting DSM-IV criteria for either major depressive disorder (n=17) or bipolar disorder (n=16) and 23 healthy control subjects.Main Outcome Measures: The primary outcome parameter was [F-18] FP-TZTP distribution volume, which is proportional to the product of receptor density and affinity and, in the case of [F-18] FP-TZTP, is known to be sensitive to endogenous acetylcholine concentrations. The relationship between illness severity, as rated using the Montgomery-Asberg Depression and Hamilton Anxiety Rating scales, and distribution volume also was assessed.Results: The mean anterior cingulate cortex distribution volume differed across groups (F-55=3.4; P=.04), and this difference was accounted for by significantly lower binding in bipolar disorder compared with both major depressive disorder and control groups.Conclusions: The mean M-2 receptor binding in subjects with bipolar disorder was reduced relative to both healthy controls and subjects with major depressive disorder, to an extent that correlated with depressive symptoms. The reduction in the bipolar disorder group could be accounted for either by a reduction in M-2 receptor density or affinity or an elevation in endogenous acetylcholine levels. To our knowledge, these data provide the first direct evidence that altered M-2 receptor function contributes to mood dysregulation in bipolar disorder.