PMID- 28604733 OWN - NLM STAT- MEDLINE DCOM- 20180730 LR - 20220311 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 42 IP - 13 DP - 2017 Dec TI - Imaging Microglial Activation in Individuals at Clinical High Risk for Psychosis: an In Vivo PET Study with [(18)F]FEPPA. PG - 2474-2481 LID - 10.1038/npp.2017.111 [doi] AB - Several lines of evidence implicate microglial activation and abnormal immune response in the etiology of psychosis. Previous positron emission tomography (PET) neuroimaging studies of the translocator protein 18 kDa, TSPO, were limited by low affinity of the first-generation radioligand, low-resolution scanners, and small sample sizes. Moreover, there is a dearth of literature on microglial activation in individuals at clinical high risk (CHR) for psychosis. We used a novel second-generation TSPO radioligand, [(18)F]FEPPA, to examine whether microglial activation is elevated in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of antipsychotic-naive CHR. Twenty-four CHR (antipsychotic-naive n=22) and 23 healthy volunteers (HV) completed a high resolution [(18)F]FEPPA PET scan and MRI. The PET data were analyzed using the validated two-tissue compartment model with arterial plasma input function with total volume of distribution (V(T)) as outcome measure. All analyses were controlled for the TSPO rs6971 polymorphism. We did not observe any significant differences in microglial activation, as indexed by [(18)F]FEPPA V(T), between CHR and HV in either the DLPFC (F((1, 44))=0.41, p=0.52) or the hippocampus (F((1, 44))=2.78, p=0.10). Exploratory associations show that in CHR, [(18)F]FEPPA V(T) was positively correlated with apathy (DLPFC: r=0.55, p=0.008; hippocampus: r=0.52, p=0.013) and state anxiety (DLPFC: r=0.60, p=0.003; hippocampus: r=0.48, p=0.024). The lack of significant group differences in [(18)F]FEPPA V(T) suggests that microglial activation is not significantly elevated in the clinical high risk state that precedes psychosis. FAU - Hafizi, Sina AU - Hafizi S AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. FAU - Da Silva, Tania AU - Da Silva T AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. FAU - Gerritsen, Cory AU - Gerritsen C AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. FAU - Kiang, Michael AU - Kiang M AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. FAU - Bagby, R Michael AU - Bagby RM AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. FAU - Prce, Ivana AU - Prce I AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. FAU - Wilson, Alan A AU - Wilson AA AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. FAU - Houle, Sylvain AU - Houle S AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. FAU - Rusjan, Pablo M AU - Rusjan PM AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. FAU - Mizrahi, Romina AU - Mizrahi R AD - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. LA - eng GR - R01 MH100043/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20170612 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Anilides) RN - 0 (N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride) RN - 0 (Pyridines) RN - 0 (Radiopharmaceuticals) RN - 0 (Receptors, GABA) RN - 0 (TSPO protein, human) SB - IM MH - Anilides MH - Anxiety/diagnostic imaging/genetics/metabolism MH - Apathy/physiology MH - Brain/*diagnostic imaging/*metabolism MH - Brain Mapping MH - Female MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Microglia/*metabolism MH - Positron-Emission Tomography MH - Prodromal Symptoms MH - Psychiatric Status Rating Scales MH - Psychotic Disorders/*diagnostic imaging/genetics/*metabolism/psychology MH - Pyridines MH - Radiopharmaceuticals MH - Receptors, GABA/genetics MH - Risk MH - Young Adult PMC - PMC5686484 EDAT- 2017/06/13 06:00 MHDA- 2018/07/31 06:00 PMCR- 2018/12/01 CRDT- 2017/06/13 06:00 PHST- 2017/02/18 00:00 [received] PHST- 2017/05/06 00:00 [revised] PHST- 2017/05/16 00:00 [accepted] PHST- 2017/06/13 06:00 [pubmed] PHST- 2018/07/31 06:00 [medline] PHST- 2017/06/13 06:00 [entrez] PHST- 2018/12/01 00:00 [pmc-release] AID - npp2017111 [pii] AID - 10.1038/npp.2017.111 [doi] PST - ppublish SO - Neuropsychopharmacology. 2017 Dec;42(13):2474-2481. doi: 10.1038/npp.2017.111. Epub 2017 Jun 12.