Imaging Neuroinflammation in Gray and White Matter in Schizophrenia: An In-Vivo PET Study With [18F]-FEPPA
Imaging Neuroinflammation in Gray and White Matter in Schizophrenia: An In-Vivo PET Study With [18F]-FEPPA
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DOI：
10.1093/schbul/sbu157
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发表时间：
2015-01-01
影响因子：
6.6
通讯作者：
Mizrahi, Romina
中科院分区：
文献类型：
--
作者：
Kenk, Miran;Selvanathan, Thiviya;Mizrahi, Romina
神经炎症和异常免疫反应与精神分裂症（SCZ）有关。过去使用正电子发射断层扫描（PET）的研究使用转运蛋白18 kDa（TSPO）靶点在体内检查SCZ患者的神经炎症，这些研究受到第一代成像剂[C-11]-PK 11195的不敏感性、使用的扫描仪和研究的小样本量的限制。本研究使用新型第二代TSPO PET放射性配体N-乙酰基-N-（2-[F-18]氟乙氧基苄基）-2-苯氧基-5-吡啶胺（[F-18]-FEPPA）来评估SCZ患者中是否存在增加的神经炎症。使用[F-18]-FEPPA和高分辨率研究断层扫描仪（HRRT）进行横断面研究。18例持续精神病症状的SCZ患者和27名健康志愿者（HV）分别从三级精神病临床环境和社区招募。所有受试者均接受了[F-18]-FEPPA PET和磁共振成像，并分析PET数据，以使用具有动脉血浆输入函数的2-组织室模型获得[F-18]-FEPPA总分布容积（V（T）），如先前验证的。根据rs6971多态性将所有受试者分为高、中、低亲和力[F-18]-FEPPA结合者，并将基因型信息纳入影像学结局分析。在灰色（F（（1，39））= 0.179，P = 0.674）或白色区域（F（（1，38））= 0.597，P = 0.445）中，两组之间的神经炎症指数（[F-18]-FEPPA V（T））无显著差异。在精神病发作和HV期间接受SCZ治疗的患者中，神经炎症缺乏显著差异，表明神经炎症过程可能发生在疾病进展的早期或受抗精神病药物治疗的影响。
Neuroinflammation and abnormal immune responses have been implicated in schizophrenia (SCZ). Past studies using positron emission tomography (PET) that examined neuroinflammation in patients with SCZ in vivo using the translocator protein 18kDa (TSPO) target were limited by the insensitivity of the first-generation imaging agent [C-11]-PK11195, scanners used, and the small sample sizes studied. Present study uses a novel second-generation TSPO PET radioligand N-acetyl-N-(2-[F-18]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([F-18]-FEPPA) to evaluate whether there is increased neuroinflammation in patients with SCZ. A cross-sectional study was performed using [F-18]-FEPPA and a high-resolution research tomograph (HRRT). Eighteen patients with SCZ with ongoing psychotic symptoms and 27 healthy volunteers (HV) were recruited from a tertiary psychiatric clinical setting and the community, respectively. All participants underwent [F-18]-FEPPA PET and magnetic resonance imaging, and PET data were analyzed to obtain [F-18]-FEPPA total volume of distribution (V (T)) using a 2-tissue compartment model with an arterial plasma input function, as previously validated. All subjects were classified as high-, medium- or low-affinity [F-18]-FEPPA binders on the basis of rs6971 polymorphism, and genotype information was incorporated into the analyses of imaging outcomes. No significant differences in neuroinflammation indexed as [F-18]-FEPPA V (T) were observed between groups in either gray (F ((1,39)) = 0.179, P = .674) or white matter regions (F ((1,38)) = 0.597, P = .445). The lack of significant difference in neuroinflammation in treated patients with SCZ in the midst of a psychotic episode and HV suggests that neuroinflammatory processes may take place early in disease progression or are affected by antipsychotic treatment.