In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis.

Bart N M van Berckel,Maqsood Yaqub,Ronald Boellaard,Ellen Jobse,Jonas Eriksson,Lot D de Witte,Adriaan A Lammertsma,Arjen L Sutterland,René S Kahn,Lieuwe de Haan,Thalia F van der Doef

doi:10.1038/npjschz.2016.31

Abstract

Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[11C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[11C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[11C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study.

Highlights

Schizophrenia is a complex and disabling disorder characterized by psychotic and cognitive symptoms, motivational impairment, and affective dysregulation
Decreased prevalence of schizophrenia has been reported in men who have used glucocorticoids for somatic disorders,[3] and some studies suggest efficacy of immunomodulatory drugs in patients with schizophrenia with the largest effect found in first-episode patients.[4,5,6]
A significant difference in specific activity of (R)[11C]PK11195 between groups was found, the injected mass of PK11195 did not differ between clinical groups, and no significant associations have been found between specific activity or injected mass and (R)-[11C]PK11195 BPND

Summary

Introduction

Schizophrenia is a complex and disabling disorder characterized by psychotic and cognitive symptoms, motivational impairment, and affective dysregulation. Its pathophysiology still remains to be elucidated. There is a growing body of evidence that immune dysfunction is involved in the pathophysiology of schizophrenia. Genetic data, derived from the latest and largest genome-wide association study, identified significant associations with immune pathways in schizophrenia.[1] Studies using information from population registries have found increased prevalence of autoimmune disorders in patients with schizophrenia and their family members.[2] decreased prevalence of schizophrenia has been reported in men who have used glucocorticoids for somatic disorders,[3] and some studies suggest efficacy of immunomodulatory drugs in patients with schizophrenia with the largest effect found in first-episode patients.[4,5,6] Serum and cerebrospinal fluid (CSF) inflammatory markers, such as cytokines produced by microglial cells, have been linked with schizophrenia and are increased predominantly in first-episode psychosis.[7]

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