Greater activation of glia, a key component of neuroinflammation, is an important process to target in neuropsychiatric illnesses. However, the magnitude of gliosis varies across cases so low-cost predictors are needed to stratify subjects for clinical trials. Here, several such blood serum measures were assessed in relation to TSPO VT, an index of translocator protein density, measured with positron emission tomography. Blood serum concentration of several products known to be synthesized by activated microglia (and to some extent astroglia) [prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), and tumor necrosis factor alpha (TNFα)], controlled by an index of peripheral inflammation [C-reactive protein (CRP)] and TSPO VT were measured in 3 cohorts: prefrontal cortex TSPO VT of 20 subjects with major depressive episodes (MDEs) from major depressive disorder (MDD); and 56 subjects with treatment resistant MDEs from MDD; and dorsal caudate TSPO VT of 20 subjects with obsessive-compulsive disorder. Ln(PGE2/CRP) and ln(TNFα/CRP) consistently correlated with TSPO VT (R2 = 0.36 to 0.11, p = 0.0030 to p = 0.0076). Assessment of threshold serum values to predict highly elevated TSPO VT, demonstrated that a positive predictive value (PPV) of 80% was possible while retaining 40% of participant samples and that receiver operating curves (ROC) ranged from 75 to 81%. Post-hoc selection of ln(CRP) was more predictive (R2 = 0.23 to 0.39, p = 0.0058 to p = 0.00013; ROC > 80%). Systematic assessment of selected peripheral inflammatory markers is promising for developing low cost predictors of TSPO VT. Marker thresholds with high PPV will improve subject stratification for clinical trials of glial targeting therapeutics.

中文翻译：

---

复制预测性血清与大脑中更大的转运蛋白分布量相关。

胶质细胞（神经炎症的关键组成部分）的更大活化是针对神经精神疾病的重要过程。然而，神经胶质细胞增生的程度因病例而异，因此需要低成本的预测因子来对临床试验的受试者进行分层。在这里，通过正电子发射断层扫描技术测量了与TSPO VT有关的几种此类血清测量指标，TSPO VT是易位蛋白密度的指标。已知由活化的小胶质细胞（某种程度上为星形胶质细胞）[前列腺素E2（PGE2），前列腺素F2α（PGF2α）和肿瘤坏死因子α（TNFα）]合成的几种产物的血清浓度在以下3个队列中测量了炎症[C反应蛋白（CRP）]和TSPO VT：20名患有重度抑郁症（MDD）的重度抑郁发作（MDE）的受试者的前额叶皮层TSPO VT；和56名患有MDD抗药性MDE的受试者；和强迫症的20名受试者的尾状背TSPO VT。Ln（PGE2 / CRP）和ln（TNFα/ CRP）与TSPO VT始终相关（R2 = 0.36至0.11，p = 0.0030至p = 0.0076）。评估血清阈值以预测TSPO VT的高度升高，表明可以在保留40％的参与者样本的同时，将80％的阳性预测值（PPV）设为正，并且接收器工作曲线（ROC）介于75％至81％之间。事后对ln（CRP）的选择更具预测性（R2 = 0.23至0.39，p = 0.0058至p = 0.00013; ROC> 80％）。对选定的外周炎性标志物的系统评估有望开发出低成本的TSPO VT预测指标。