Imaging Microglial Activation in Untreated First-Episode Psychosis: A PET Study With [18F]FEPPA.
OBJECTIVE
Neuroinflammation and abnormal immune responses are increasingly implicated in the pathophysiology of schizophrenia. Previous positron emission tomography (PET) studies targeting the translocator protein 18 kDa (TSPO) have been limited by high nonspecific binding of the first-generation radioligand, low-resolution scanners, small sample sizes, and psychotic patients being on antipsychotics or not being in the first episode of their illness. The present study uses the novel second-generation TSPO PET radioligand [18F]FEPPA to evaluate whether microglial activation is elevated in the dorsolateral prefrontal cortex and hippocampus of untreated patients with first-episode psychosis.


METHODS
Nineteen untreated patients with first-episode psychosis (14 of them antipsychotic naive) and 20 healthy volunteers underwent a high-resolution [18F]FEPPA PET scan and MRI. Dynamic PET data were analyzed using the validated two-tissue compartment model with arterial plasma input function with total volume of distribution (VT) as outcome measure. All analyses were corrected for TSPO rs6971 polymorphism (which is implicated in differential binding affinity).


RESULTS
No significant differences were observed between patients and healthy volunteers in microglial activation, as indexed by [18F]FEPPA VT, in either the dorsolateral prefrontal cortex or the hippocampus. There were no significant correlations between [18F]FEPPA VTand duration of illness, clinical presentation, or neuropsychological measures after adjusting for multiple testing.


CONCLUSIONS
The lack of significant differences in [18F]FEPPA VTbetween groups suggests that microglial activation is not present in first-episode psychosis.
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Sina
S
Hafizi
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Huai-Hsuan
HH
Tseng
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Naren
N
Rao
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Thiviya
T
Selvanathan
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Miran
M
Kenk
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Richard P
RP
Bazinet
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Ivonne
I
Suridjan
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Alan A
AA
Wilson
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Jeffrey H
JH
Meyer
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Gary
G
Remington
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Sylvain
S
Houle
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Pablo M
PM
Rusjan
From the Research Imaging Centre and the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto; the Departments of Psychiatry and of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto; and the Institute of Medical Science, University of Toronto, Toronto.
Romina
R
Mizrahi
D000328:Adult; D000813:Anilides; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000502:physiology*; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011618:Psychotic Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D011725:Pyridines; D018079:Receptors, GABA / Q000235:genetics / Q000502:physiology*; D012016:Reference Values; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D013223:Statistics as Topic; D055815:Young Adult
D000813:Anilides; C530438:N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride; D011725:Pyridines; D018079:Receptors, GABA; C499229:TSPO protein, human
Imaging; Microglia; Neuroinflammation; PET; Psychosis; Schizophrenia