Replicating predictive serum correlates of greater translocator protein distribution volume in brain

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.