Frankle W Gordon, Lombardo Ilise, Kegeles Lawrence S, Slifstein Mark, Martin John H, Huang Yiyun, Hwang Dah-Ren, Reich Elisa, Cangiano Claudine, Gil Roberto, Laruelle Marc, Abi-Dargham Anissa
Departments of Psychiatry and Radiology, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Psychopharmacology (Berl). 2006 Dec;189(2):155-64. doi: 10.1007/s00213-006-0543-8. Epub 2006 Sep 5.
Postmortem and positron emission tomography (PET) studies have reported several alterations in serotonin 1A receptor (5-HT(1A)) binding parameters in patients with schizophrenia. This study examines 5-HT(1A) availability in vivo in individuals with schizophrenia and schizo-affective disorder.
Twenty-two medication-free individuals with schizophrenia or schizo-affective disorder and 18 healthy subjects underwent PET scans with [(11)C]WAY 100635. Regional distribution volumes (V(T), in milliliters per gram) were derived using a two-tissue compartment kinetic model. Outcome measures for 5-HT(1A) availability included binding potential (BP) and the specific to nonspecific equilibrium partition coefficient (V(3)''). Eleven brain regions with high density of 5-HT(1A) were included in the analysis.
No significant differences were observed in regional BP or V(3)'' between patients and controls. No significant relationships were observed between regional 5-HT(1A) availability and symptom severity.
The postmortem literature reports increased 5-HT(1A) binding in the prefrontal cortex in schizophrenia. This study did not detect differences in 5-HT(1A) binding. Whereas in two recently published PET studies, one reports increased binding in the temporal lobe while the other reports decreased binding in the amygdala. These inconsistencies suggest that the alterations demonstrated in postmortem studies cannot be reliably detected at the resolution achieved with PET. This raises the question as to whether major changes in the level of expression of the 5-HT(1A) receptor play a role in the pathophysiology of schizophrenia.
尸检和正电子发射断层扫描(PET)研究报告称,精神分裂症患者的5-羟色胺1A受体(5-HT(1A))结合参数存在多种改变。本研究检测了精神分裂症和分裂情感性障碍患者体内5-HT(1A)的可用性。
22名未服用药物的精神分裂症或分裂情感性障碍患者以及18名健康受试者接受了用[(11)C]WAY 100635进行的PET扫描。使用双组织隔室动力学模型得出区域分布容积(V(T),单位为毫升/克)。5-HT(1A)可用性的结果指标包括结合势(BP)和特异性与非特异性平衡分配系数(V(3)'')。分析纳入了11个5-HT(1A)高密度的脑区。
患者与对照组之间在区域BP或V(3)''上未观察到显著差异。在区域5-HT(1A)可用性与症状严重程度之间未观察到显著关系。
尸检文献报道精神分裂症患者前额叶皮质中5-HT(1A)结合增加。本研究未检测到5-HT(1A)结合的差异。而在最近发表的两项PET研究中,一项报告颞叶结合增加,另一项报告杏仁核结合减少。这些不一致表明,尸检研究中显示的改变在PET所达到的分辨率下无法可靠检测到。这就提出了一个问题,即5-HT(1A)受体表达水平的重大变化是否在精神分裂症的病理生理学中起作用。