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使用[11C]DASB和正电子发射断层扫描评估双相情感障碍中的5-羟色胺转运体结合。

Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography.

作者信息

Cannon Dara M, Ichise Masanori, Fromm Stephen J, Nugent Allison C, Rollis Denise, Gandhi Shilpa K, Klaver Jacqueline M, Charney Dennis S, Manji Husseini K, Drevets Wayne C

机构信息

Mood and Anxiety Disorders Program, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-2670, USA.

出版信息

Biol Psychiatry. 2006 Aug 1;60(3):207-17. doi: 10.1016/j.biopsych.2006.05.005.

Abstract

BACKGROUND

Evidence from neuroimaging post-mortem, and genetic studies suggests that bipolar disorder (BD) is associated with abnormalities of the serotonin-transporter (5-HTT) system. Because of various limitations of these studies, however, it has remained unclear whether 5-HTT binding is abnormal in unmedicated BD-subjects. This study used PET and [(11)C]DASB, a radioligand that afforded higher sensitivity and specificity for the 5-HTT than previously available radioligands, to compare 5-HTT binding between BD and control subjects.

METHODS

The 5-HTT binding-potential (BP) was assessed in 18 currently-depressed, unmedicated BD-subjects and 37 healthy controls using PET and [(11)C]DASB.

RESULTS

In BD, the mean 5-HTT BP was increased in thalamus, dorsal cingulate cortex (DCC), medial prefrontal cortex and insula and decreased in the brainstem at the level of the pontine raphe-nuclei. Anxiety ratings correlated positively with 5-HTT BP in insula and DCC, and BP in these regions was higher in subjects manifesting pathological obsessions and compulsions relative to BD-subjects lacking such symptoms. Subjects with a history of suicide attempts showed reduced 5-HTT binding in the midbrain and increased binding in anterior cingulate cortex versus controls and to BD-subjects without attempts.

CONCLUSIONS

This is the first study to report abnormalities in 5-HTT binding in unmedicated BD-subjects. The direction of abnormality in the brainstem was opposite to that found in the cortex, thalamus, and striatum. Elevated 5-HTT binding in the cortex may be related to anxiety symptoms and syndromes associated with BD.

摘要

背景

神经影像学尸检和基因研究的证据表明,双相情感障碍(BD)与血清素转运体(5-HTT)系统异常有关。然而,由于这些研究存在各种局限性,未经药物治疗的BD患者的5-HTT结合是否异常仍不清楚。本研究使用正电子发射断层扫描(PET)和[(11)C]DASB(一种对5-HTT具有比以前可用的放射性配体更高灵敏度和特异性的放射性配体)来比较BD患者和对照受试者之间的5-HTT结合情况。

方法

使用PET和[(11)C]DASB对18名目前处于抑郁状态、未经药物治疗的BD患者和37名健康对照者的5-HTT结合潜力(BP)进行评估。

结果

在BD患者中,丘脑、背侧扣带回皮质(DCC)、内侧前额叶皮质和脑岛的平均5-HTT BP升高,而在脑桥中缝核水平的脑干中降低。焦虑评分与脑岛和DCC中的5-HTT BP呈正相关,相对于没有此类症状的BD患者,表现出病理性强迫观念和强迫行为的受试者在这些区域的BP更高。有自杀未遂史的受试者与对照组和无自杀未遂史的BD患者相比,中脑的5-HTT结合减少,前扣带回皮质的结合增加。

结论

这是第一项报告未经药物治疗的BD患者5-HTT结合异常的研究。脑干中异常的方向与皮质、丘脑和纹状体中发现的相反。皮质中5-HTT结合升高可能与BD相关的焦虑症状和综合征有关。

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