Ertugrul Aygun, Volkan-Salanci Bilge, Basar Koray, Karli Oguz Kader, Demir Basaran, Ergun Eser Lay, Senturk Senem, Erbas Belkis, Cila Aysenur, Ulug Berna
Hacettepe University, Faculty of Medicine, Department of Psychiatry, Ankara, Turkey.
Psychiatry Res. 2009 Nov 30;174(2):121-9. doi: 10.1016/j.pscychresns.2009.04.007. Epub 2009 Oct 17.
The purpose of this study was to investigate the effect of clozapine on regional cerebral blood flow (rCBF) and its relationship with response to treatment. In addition, we aimed to study the influence of clozapine on proton magnetic resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning, and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after the initiation of clozapine treatment. In 10 of these patients intermediate-echo (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8 weeks. Clozapine treatment increased the right frontal (superior and medial)/caudate perfusion ratio in the whole group, while it increased bilateral frontal (superior and medial)/caudate perfusion ratios in treatment responders. In addition, percentage changes in left and right frontal (superior and medial)/caudate perfusion ratios compared to the baseline were higher in treatment responders than in non-responders. The improvement in attention was related to the increase in percentage change in the right frontal (superior and medial)/caudate perfusion ratio, while the improvement in verbal fluency was related to the increase in percentage changes in both right and left frontal (superior and medial)/caudate perfusion ratios and to right frontal (superior and medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus perfusion could explain 32% of the variability of percentage improvements in psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology score was inversely correlated with the baseline NAA/Cre ratio. An increased NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in fronto-striato-thalamic circuitry that changes with clozapine, especially in the responders, while (1)H-MRS results indicate a supportive effect of clozapine on neuronal integrity.
本研究的目的是调查氯氮平对局部脑血流量（rCBF）的影响及其与治疗反应的关系。此外，我们旨在研究氯氮平对一组患者背外侧前额叶皮质（DLPFC）质子磁共振波谱（(1)H-MRS）结果的影响。在基线和氯氮平治疗开始8周后，对22例患者的精神病理学、神经认知功能和SPECT成像进行了评估。在这些患者中的10例中，还在基线和8周后进行了中间回波（TE：135 ms）单体素(1)H-MRS检查。氯氮平治疗使全组右侧额叶（上和内侧）/尾状核灌注比值增加，而在治疗反应者中双侧额叶（上和内侧）/尾状核灌注比值增加。此外，与基线相比，治疗反应者左右额叶（上和内侧）/尾状核灌注比值的百分比变化高于无反应者。注意力的改善与右侧额叶（上和内侧）/尾状核灌注比值百分比变化的增加有关，而语言流畅性的改善与左右额叶（上和内侧）/尾状核灌注比值百分比变化的增加以及右侧额叶（上和内侧）/丘脑灌注有关。基线额叶（上和内侧）/丘脑灌注可解释精神病理学改善百分比变异性的32%。(1)H-MRS显示基线PANSS总体精神病理学评分与基线NAA/Cre比值呈负相关。(1)H-MRS还显示氯氮平治疗8周后DLPFC中NAA/Cre比值增加。我们的SPECT成像结果表明额-纹状体-丘脑回路存在失衡，这种失衡会随着氯氮平的使用而改变，尤其是在反应者中，而(1)H-MRS结果表明氯氮平对神经元完整性有支持作用。
