title: In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence.
abstract: Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol-dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [11C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol-dependent subjects. Alcohol-dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink. Linear mixed modeling of partial-volume-corrected [11C]PBR28 data revealed a main effect of alcohol dependence (P=0.034), corresponding to 10% lower TSPO levels in alcohol-dependent subjects. Within this group, exploratory analyses found a negative association of TSPO levels in the hippocampus and striatum with alcohol dependence severity (P<0.035). Peripheral immune response was assessed in a subset of subjects by measuring cytokine expression from monocytes cultured both in the presence and absence of lipopolysaccharide. Peripheral monocyte response to lipopolysaccharide stimulation was lower in alcohol-dependent subjects compared with controls for the proinflammatory cytokines interleukin-6 and interleukin-8. Thus, alcohol-dependent individuals exhibited less activated microglia in the brain and a blunted peripheral proinflammatory response compared with controls. These findings suggest a role for pharmaceuticals tuning the neuroimmune system as therapeutics for alcohol dependence.
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.|Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Hillmer
authors.affiliation: Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Sandiego
authors.affiliation: UCB Pharma, Braine-l'Alleud, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Hannestad
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.|Connecticut Mental Health Center, New Haven, CT, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Angarita
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: McGovern
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.|Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: O'Connor
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.|Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: O'Malley
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.|Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.|Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Cosgrove
mesh_terms: D000081:Acetamides; D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D059906:Neuroimaging; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; D016207:Cytokines; D008070:Lipopolysaccharides; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human