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

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Abstract

Schizophrenia is thought to be associated with inflammation [1]. 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 [2,3] indicate the presence of microglial activation in schizophrenia but these studies might be confounded by medication effects. We present preliminary findings from a study investigating neuroinflammation in both medicated and unmedicated schizophrenic patients.Ten patients with schizophrenia and ten matched controls underwent a 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 [4]. Of the 10 patients, 7 were antipsychotic-free (>= 3 months) and 3 were receiving antipsychotic medication (risperidone long-acting injection).Globally, cortical BPND was higher in schizophrenia patients compared to controls, with a significant main effect of group (p < 0.001) across 7 cortical ROIs. Post-hoc t-tests showed significantly higher binding in the anterior cingulate (p=0.002) in patients. On subgroup analysis, mean cortical BPND values were higher in medicated compared to antipsychotic-free patients (p=0.001). Globally, BPND did not differ between antipsychotic-free patients and healthy controls (p=0.208). However, the increased binding in the anterior cingulate remained significant (p=0.012).The increased microglial activation inpatients seems to be being driven by the subgroup of medicated patients. However, when comparing antipsychotic-free patients with controls, increased microglial activation is present in the anterior cingulate, suggesting that this focal neuroinflammation may be disease-related as opposed to medication-related.References[1] Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E (2008): Inflammatory cytokine alterations in schizophrenia: A systematic quantitative review. Biological Psychiatry. 63: 801–808.[2] van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, et al. (2008): Microglia Activation in Recent-Onset Schizophrenia: A Quantitative (R)-C-11 PK11195 Positron Emission Tomography Study. Biological Psychiatry. 64: 820–822.[3] Doorduin J, de Vries EFJ, Willemsen ATM, de Groot JC, Dierckx RA, Klein HC (2009): Neuroinflammation in Schizophrenia-Related Psy-chosis: A PET Study. Journal of Nuclear Medicine. 50: 1801–1807.[4] Lammertsma AA, Hume SP (1996): Simplified reference tissue model for PET receptor studies. Neuroimage. 4: 153–158.

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