117.3 Imaging Microglial Activation in Clinical High Risk for Psychosis and Untreated First-Episode Psychosis: A PET StudyW 18FFEPPA

摘要

>Background: A role of the immune system in the pathogenesis of schizophrenia is supported by convergence of evidence from genetic, epidemiology, and preclinical studies. Previous positron emission tomography (PET) studies using radioligands that target the translocator protein 18kDa (TSPO) in patients with schizophrenia in vivo were limited by radioligand used, resolution of scanners used, and the confounding effect of antipsychotic medications. There is a dearth of evidence on the state of early stages of the illness such as the first-episode psychosis (FEP) and clinical high risk for psychosis (CHR). >Methods: Using a second-generation TSPO radioligand, [18F]FEPPA, and a high-resolution research tomograph (HRRT), we examined microglial activation in dorsolateral prefrontal cortex (DLPFC) and hippocampus of CHR and FEP. Dynamic PET data were analyzed using a 2-tissue compartment model with an arterial plasma input function to obtain [18F]FEPPA total volume of distribution (VT), as previously validated. Based on their rs6971 polymorphism, subjects were classified as high-, medium- or low-affinity [18F]FEPPA binders, and all the analyses were controlled for genotype. >Results: 24 (mean age = 21.21, SD = 3.35) CHR and 19 patients with untreated FEP (mean age = 27.53, SD = 6.78), and 20 healthy volunteers (mean age =27.75, SD = 8.77) underwent PET and magnetic resonance imaging. No significant differences in [18F]FEPPA VT in DLPFC and hippocampus were found between different diagnostic groups. Explorative association analyses found a trend toward significant association between RBANS total score and [18F]FEPPA VT in hippocampus of FEP (r = .50, P = .04). In CHR, apathy score was associated with [18F]FEPPA VT in DLPFC (r = .604, P = .003) and hippocampus (r = .574, P = .005). Moreover, [18F]FEPPA VT in DLPFC was associated with state anxiety score (r = .56, P = .007). >Conclusion: This is the largest study examined microglial activation in the early stages of psychosis using a standard methodology without the confound of antipsychotic medications. Our findings suggest that microglial activation is not present in early stages of psychosis (i.e., CHR and FEP).