title: Glucose metabolism in the insula and cingulate is affected by systemic inflammation in humans.
abstract: Depression is associated with systemic inflammation, and the systemic inflammation caused by endotoxin administration elicits mild depressive symptoms such as fatigue and reduced interest. The neural correlates of depressive symptoms that result from systemic inflammation are poorly defined. The aim of this study was to use (18)F-FDG PET to identify brain regions involved in the response to endotoxin administration in humans.
  
  
  METHODS
  Nine healthy subjects received double-blind endotoxin (0.8 ng/kg) and placebo on different days. (18)F-FDG PET was used to measure differences in the cerebral metabolic rate of glucose in the following regions of interest: insula, cingulate, and amygdala. Serum levels of tumor necrosis factor-α and interleukin-6 were used to gauge the systemic inflammatory response, and depressive symptoms were measured with the Montgomery-Åsberg Depression Rating Scale and other scales.
  
  
  RESULTS
  Endotoxin administration was associated with an increase in Montgomery-Åsberg Depression Rating Scale, increased fatigue, reduced social interest, increased levels of inflammatory cytokines, higher normalized glucose metabolism (NGM) in the insula, and, at a trend level, lower NGM in the cingulate. Secondary analyses of insula and cingulate subregions indicated that these changes were driven by the right anterior insula and the right anterior cingulate. There was a negative correlation between peak cytokine levels and change in social interest and between peak cytokine levels and change in insula NGM. There was a positive correlation between the change in NGM in the insula and change in social interest.
  
  
  CONCLUSIONS
  Systemic inflammation in humans causes an increase in depressive symptoms and concurrent changes in glucose metabolism in the insula and cingulate-brain regions that are involved in interoception, positive emotionality, and motivation.
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. jonas.hannestad@yale.edu
authors.forename: Jonas
authors.initials: J
authors.lastname: Hannestad
authors.forename: Kalyani
authors.initials: K
authors.lastname: Subramanyam
authors.forename: Nicole
authors.initials: N
authors.lastname: Dellagioia
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta-Wilson
authors.forename: David
authors.initials: D
authors.lastname: Weinzimmer
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001519:Behavior / Q000187:drug effects; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography
chemical_list: D004731:Endotoxins; D019788:Fluorodeoxyglucose F18; D005947:Glucose