Adams Karen H, Hansen Elsebeth S, Pinborg Lars H, Hasselbalch Steen G, Svarer Claus, Holm Søren, Bolwig Tom G, Knudsen Gitte M
Neurobiology Research Unit (NRU), University Hospital of Copenhagen, Denmark.
Int J Neuropsychopharmacol. 2005 Sep;8(3):391-401. doi: 10.1017/S1461145705005055. Epub 2005 Apr 1.
The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-compulsive disorder (OCD) may have alterations in their cerebral serotonergic (5-HT) receptor system, and previous neuroimaging studies of OCD patients have shown abnormalities in several fronto-subcortical regions. In this study we investigated cerebral 5-HT(2A) receptor binding in 15 untreated OCD patients and in 15 age- and gender-matched healthy volunteers by magnetic resonance imaging and [(18)F]altanserin positron emission tomography (PET). Eleven of the patients were rescanned with PET after receiving treatment with a selective serotonin reuptake inhibitor (SSRI). The distribution volumes of specific tracer binding (DV(3)') were calculated for 12 brain regions, and comparisons were made between: (1) healthy volunteers vs. untreated OCD patients, (2) healthy volunteers vs. treated OCD patients, and (3) OCD patients before and during treatment. When comparing the distribution volume for specific fronto-subcortical brain regions, significantly higher values were recorded in the caudate nuclei in OCD patients (DV(3)': 0.24+/-0.14) compared to the healthy control group (DV(3)': 0.15+/-0.13) (p<0.05, Wilcoxon matched-pairs test). This difference between groups was not present after treatment with SSRIs. There was no correlation between the severity of OCD symptoms and 5-HT(2A )receptor binding. An increase in 5-HT(2A) receptor binding is found in the caudate nuclei of untreated patients with OCD. The up-regulation in 5-HT(2A) receptors might be compensatory for a lack of serotonin in the feedback loop between the thalamus and orbito-frontal cortex, the caudate nuclei, and the globus pallidus.
作用于血清素的药物的药理功效表明，强迫症（OCD）患者的大脑血清素（5-HT）受体系统可能存在改变，先前对OCD患者的神经影像学研究已显示出几个额-皮质下区域存在异常。在本研究中，我们通过磁共振成像和[18F]阿坦色林正电子发射断层扫描（PET），对15名未经治疗的OCD患者以及15名年龄和性别匹配的健康志愿者的大脑5-HT（2A）受体结合情况进行了研究。11名患者在接受选择性5-羟色胺再摄取抑制剂（SSRI）治疗后，再次接受PET扫描。计算了12个脑区的特异性示踪剂结合分布容积（DV（3）'），并进行了以下比较：（1）健康志愿者与未经治疗的OCD患者；（2）健康志愿者与接受治疗的OCD患者；（3）OCD患者治疗前和治疗期间。比较特定额-皮质下脑区的分布容积时，OCD患者尾状核中的值（DV（3）'：0.24±0.14）显著高于健康对照组（DV（3）'：0.15±0.13）（p<0.05，Wilcoxon配对检验）。用SSRI治疗后，组间差异消失。OCD症状的严重程度与5-HT（2A）受体结合之间无相关性。在未经治疗的OCD患者的尾状核中发现5-HT（2A）受体结合增加。5-HT（2A）受体上调可能是对丘脑与眶额皮质、尾状核和苍白球之间反馈回路中血清素缺乏的一种代偿。
