Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study.
Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study.
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DOI：
10.1176/appi.ajp.2015.14101358
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Howes OD
中科院分区：
文献类型：
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作者：
Bloomfield PS;Selvaraj S;Veronese M;Rizzo G;Bertoldo A;Owen DR;Bloomfield MA;Bonoldi I;Kalk N;Turkheimer F;McGuire P;de Paola V;Howes OD
确定在出现亚临床症状的未用药受试者中，使用转运蛋白正电子发射断层成像（PET）测量的小胶质细胞活性是否增加，表明他们处于精神病的超高风险，并确定在控制转运蛋白特异性遗传多态性后，精神分裂症中的小胶质细胞活性是否升高。在这里，我们使用第二代放射性配体[11C]PBR28和PET来成像精神病超高风险受试者大脑中的小胶质细胞活性。受试者从早期干预中心招募。我们还对一组精神分裂症患者和健康对照进行了成像以进行比较，共有56名受试者完成了研究。在筛选时，对受试者进行基因分型，以解释编码18Kd转运蛋白的基因中的rs6971多态性。主要结果测量是总灰质[11 C]PBR28结合率，代表小胶质细胞活性。与匹配的对照组相比，在极高风险受试者中灰质中的[11C]PBR28结合率升高（p=0.004，F= 10.3，Cohen’s d >1.2），并且与症状严重程度正相关（r= 0.730，p<0.01）。精神分裂症患者的小胶质细胞活性也高于对照组（p<0.001，F= 20.8，Cohen’s d >1.7）。小胶质细胞活性在精神分裂症和具有亚临床症状的精神病超高风险受试者中升高，并且与风险症状严重程度相关。这表明神经炎症与精神病和相关疾病的风险以及亚临床症状的表达有关。对超高风险受试者的随访将确定这是否是精神分裂症后期发展的特异性或一般风险因素。
To determine whether microglial activity, measured using translocator-protein positron emission tomographic imaging (PET), is increased in unmedicated subjects presenting with sub-clinical symptoms indicating they are at ultra high risk of psychosis, and to determine if it is elevated in schizophrenia after controlling for a translocator specific genetic polymorphism. Here we use the second generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of subjects at ultra high risk for psychosis. Subjects were recruited from early intervention centres. We also imaged a cohort of patients with schizophrenia and healthy controls for comparison, in total 56 subjects completed the study. At screening, subjects were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd Translocator Protein. The main outcome measure was total grey matter [11C]PBR28 binding ratio, representing microglial activity. [11C]PBR28 binding ratio in grey matter was elevated in ultra high risk subjects, compared to matched controls, (p=0.004, F= 10.3, Cohen’s d >1.2), and was positively correlated with symptom severity (r= 0.730, p<0.01). Patients with schizophrenia also demonstrated elevated microglial activity with respect to matched controls (p<0.001, F= 20.8, Cohen’s d >1.7). Microglial activity is elevated in schizophrenia and in subjects with sub-clinical symptoms who are at ultra high risk of psychosis, and is related to at risk symptom severity. This indicates that neuroinflammation is linked to the risk of psychosis and related disorders, and the expression of sub-clinical symptoms. Follow up of ultra high risk subjects will determine whether this is specific to the later development of schizophrenia or risk factors in general.