title: The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: a [¹¹C]PBR28 PET study.
abstract: Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however, postmortem studies have not convincingly shown that there is neuroinflammation in depression. The purpose of this study was to use positron emission tomography (PET) with [¹¹C]PBR28, which binds to the neuroinflammation marker translocator protein 18 kDa (TSPO), to compare the level of TSPO between individuals with depression and control subjects. Ten individuals who were in an acute episode of major depression and 10 control subjects matched for TSPO genotype and other characteristics had a PET scan with arterial input function to quantify levels of TSPO in brain regions of interest (ROIs). Total volume of distribution (VT) of [¹¹C]PBR28 was used as a measure of total ligand binding. The primary outcome was the difference in VT between the two groups; this was assessed using a linear mixed model with group as a between-subject factor and region as a within-subject factor. There was no statistically significant difference in [¹¹C]PBR28 binding (VT) between the two groups. In fact, 7 of 10 individuals with depression had lower [¹¹C]PBR28 binding in all ROIs compared to their respective genotype-matched control subjects. Future studies are needed to determine whether individuals with mild-to-moderate depression have lower TSPO levels and to assess whether individuals with severe depression and/or with elevated levels of systemic inflammation might have higher TSPO levels than control subjects.
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. Electronic address: jonas.hannestad@yale.edu.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hannestad
authors.forename: Nicole
authors.initials: N
authors.lastname: DellaGioia
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.forename: Keunpoong
authors.initials: K
authors.lastname: Lim
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Jae-Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D003863:Depression / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020078:Neurogenic Inflammation / Q000097:blood / Q000276:immunology* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000276:immunology; D018079:Receptors, GABA / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002250:Carbon Radioisotopes; D018079:Receptors, GABA; C499229:TSPO protein, human; D002097:C-Reactive Protein
keywords: Depression; Microglia; Neuroinflammation; PET; Translocator protein 18kDa