Neuroinflammation in schizophrenia and effects of antipsychotic medication - a PET study.

Introduction: Schizophrenia is a debilitating mental disorder whose pathogenesis is still not entirely clear. However, mounting evidence suggests that immune function is involved and a consistent finding is that peripheral inflammatory cytokines are raised in schizophrenia [1]. Whether inflammation is also apparent in the brain however, is yet to be established. Microglial activation, a measure of neuroinflammation, can be quantified using PET ligands specific for the 18kDa translocator protein (TSPO) which is overexpressed by activated microglia. Initial PET studies have shown evidence for microglial activation in schizophrenia [2,3] but these studies might be confounded by medication effects and mild symptom severity. We present preliminary findings from an ongoing study investigating neuroinflammation in both medicated and unmedicated schizophrenic patients.Methods: Ten patients (6 males, mean age ±SD 32±8.8) with a diagnosis of DSM-IV schizophrenia of at least moderate severity (PANSS score 85±8.9) and ten age- and gender-matched controls (6 males, age 32.6±10.2) underwent a 60 minute dynamic PET scan with TSPO tracer [11C](R)-PK11195 using the High Resolution Research Tomograph (HRRT). A grey matter cerebellum input function was used to generate parametric maps of BPND using the simplified reference tissue method. A maximum probability brain atlas was applied to the parametric brain maps to give readouts from each ROI. Of the 10 patients, 7 were antipsychotic-free for at least 3 months prior to scanning and 3 were receiving regular antipsychotic medication (risperidone long-acting injection (LAI; bi-weekly). Patients had no alcohol or substance misuse and were medically healthy. Results: Globally, mean cortical BPND was higher in schizophrenia patients (0.09±0.07) compared to controls (0.05±0.02). A univariate ANOVA revealed a significant main effect of group [F(1,6) = 15.84, p