Interaction between TSPO-a neuroimmune marker-and redox status in clinical high risk for psychosis: a PET-MRS study

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 43; no. 8; pp. 1700 - 1705
• Main Authors: Hafizi, Sina, Da Silva, Tania, Meyer, Jeffrey H, Kiang, Michael, Houle, Sylvain, Remington, Gary, Prce, Ivana, Wilson, Alan A, Rusjan, Pablo M, Sailasuta, Napapon, Mizrahi, Romina
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2018; Springer International Publishing
• Subjects: Anilides; Antioxidants; Antipsychotics; Brain; Brain - diagnostic imaging; Brain - metabolism; Female; Genotypes; Glutathione; Glutathione - metabolism; Humans; Immune response; Magnetic resonance spectroscopy; Male; Mental disorders; Molecular chains; Molecular modelling; NMR; Nuclear magnetic resonance; Oxidation-Reduction; Oxidative stress; Positron emission tomography; Prefrontal cortex; Prodromal Symptoms; Proton magnetic resonance; Proton Magnetic Resonance Spectroscopy; Psychosis; Psychotic Disorders - diagnostic imaging; Psychotic Disorders - metabolism; Pyridines; Radiopharmaceuticals; Receptors, GABA - metabolism; Risk; Schizophrenia; Young Adult
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/s41386-018-0061-5

Altered neuroimmune response and oxidative stress have both been implicated in the pathophysiology of schizophrenia. While preclinical studies have proposed several pathways regarding potential interactions between oxidative stress and neuroimmune imbalance in the development of psychosis, the molecular mechanisms underlying this interaction are not yet understood. To date, no study has investigated this link in vivo in the human brain. We conducted the first in vivo study linking translocator protein 18  kDa (TSPO) expression and glutathione (a major brain antioxidant and a marker for redox status) in the medial prefrontal cortex (mPFC) of a relatively large sample of participants (N = 48) including 27 antipsychotic-naïve individuals at clinical high risk for psychosis and 21 matched healthy volunteers using high-resolution PET with TSPO radioligand, [ F]FEPPA, and 3T proton magnetic resonance spectroscopy ( H MRS). The omnibus model (including TSPO genotype as covariate) was significant (F  = 10.01, p < 0.001), with a significant group interaction (t = -2.10, p = 0.04), suggesting a different relation between [ F]FEPPA V and glutathione in each clinical group. In healthy volunteers, but not in individuals at clinical high risk for psychosis, we found a significant negative association between glutathione levels and [ F]FEPPA V (r = -0.60, p = 0.006). We observed no significant group differences with respect to [ F]FEPPA V or glutathione levels. These findings suggest an abnormal interaction between TSPO expression and redox status in the clinical high risk states for psychosis.