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 V_T, 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 (PGF_2α), and tumor necrosis factor alpha (TNF_α)], controlled by an index of peripheral inflammation [C-reactive protein (CRP)] and TSPO V_T were measured in 3 cohorts: prefrontal cortex TSPO V_T 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 V_T of 20 subjects with obsessive-compulsive disorder. Ln(PGE₂/CRP) and ln(TNF_α/CRP) consistently correlated with TSPO V_T (R² = 0.36 to 0.11, p = 0.0030 to p = 0.0076). Assessment of threshold serum values to predict highly elevated TSPO V_T, 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 V_T. Marker thresholds with high PPV will improve subject stratification for clinical trials of glial targeting therapeutics.