State-associated changes in longitudinal [18F]-PBR111 TSPO PET imaging of psychosis patients: Evidence for the accelerated ageing hypothesis?
State-associated changes in longitudinal [18F]-PBR111 TSPO PET imaging of psychosis patients: Evidence for the accelerated ageing hypothesis?
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DOI：
10.1016/j.bbi.2018.11.318
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发表时间：
2019-03-01
影响因子：
15.1
通讯作者：
Morrens, Manuel
中科院分区：
文献类型：
--
作者：
De Picker, Livia;Ottoy, Julie;Morrens, Manuel
目的：通过纵向评价从急性精神病到治疗后随访的临床过程中的区域示踪剂摄取，并与健康对照组进行比较，确定是否可以在精神病患者中识别出与小胶质细胞活性状态相关的变化（采用转运蛋白正电子发射断层扫描（TSPO PET）测量）。方法：采用第二代放射性配体[F-18]-PBR 111 TSPO PET-CT对14例男性精神病患者和17例年龄匹配的健康对照者进行纵向动态显像。患者首先在急性精神病发作期间进行扫描，然后在治疗后进行第二次扫描。先前受试者rs6917多态性的基因分型区分了高亲和力和混合亲和力结合剂。主要结果是区域分布容积（V-T），代表TSPO结合。CRP，细胞因子和犬尿氨酸的血浆浓度测定在每个timepoint.Results：我们发现一个显着的三因素之间的相互作用的时间扫描，年龄和队列（皮质灰质F6.50，P.020）。在精神病状态下，两个队列之间存在V-T的依赖性差异，但在随访时不存在。患者V-T随时间的相对变化与年龄相关（皮质灰质Pearson r.574）。PANSS阳性子量表评分与精神病期间的区域V-T相关（皮质灰质r.767）。血浆CRP和喹啉酸独立与较低的V-T。结论：我们确定了一个不同的年龄依赖性模式TSPO结合精神病后续在我们的男性精神病患者队列。我们建议未来在精神病患者中进行TSPO PET研究，以区分临床状态并考虑潜在的年龄相关影响。
Objective: To determine whether state-associated changes in microglial activity, measured with translocator-protein positron emission tomography (TSPO PET), can be identified in psychosis patients through longitudinal evaluation of their regional tracer uptake over the clinical course from acute psychosis to post-treatment follow-up, and comparison to healthy controls. We also evaluated the relation between tracer uptake, clinical symptoms and peripheral immunological markers.Method: Second-generation radioligand [F-18]-PBR111 TSPO PET-CT was used for longitudinal dynamic imaging in 14 male psychosis patients and 17 male age-matched healthy control subjects. Patients were first scanned during an acute psychotic episode followed by a second scan after treatment. Prior genotyping of subjects for the rs6917 polymorphism distinguished high- and mixed-affinity binders. The main outcome was regional volume of distribution (V-T), representing TSPO binding. Plasma concentrations of CRP, cytokines and kynurenines were measured at each timepoint.Results: We found a significant three-way interaction between time of scan, age and cohort (cortical grey matter F6.50, p.020). Age-dependent differences in V-T existed between cohorts during the psychotic state, but not at follow-up. Patients' relative change in V-T over time correlated with age (cortical grey matter Pearson's r.574). PANSS positive subscale scores correlated with regional V-T during psychosis (cortical grey matter r.767). Plasma CRP and quinolinic acid were independently associated with lower V-T.Conclusions: We identified a differential age-dependent pattern of TSPO binding from psychosis to follow-up in our cohort of male psychosis patients. We recommend future TSPO PET studies in psychosis patients to differentiate between clinical states and consider potential age-related effects.