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
Mood and Anxiety Disorders Program, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-2670, USA.
Biol Psychiatry. 2006 Aug 1;60(3):207-17. doi: 10.1016/j.biopsych.2006.05.005.
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.
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.
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.
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.
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。
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。
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。
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。