title: Association of plasma interleukin-18 levels with emotion regulation and μ-opioid neurotransmitter function in major depression and healthy volunteers.
abstract: BACKGROUND
  Alterations in central neurotransmission and immune function have been documented in major depression (MDD). Central and peripheral endogenous opioids are linked to immune functioning in animal models, stress-activated, and dysregulated in MDD. We examined the relationship between μ-opioid receptor (OR)-mediated neurotransmission and a proinflammatory cytokine (interleukin [IL]-18).
  
  
  METHODS
  We studied 28 female subjects (14 MDDs, 14 control subjects) with positron emission tomography and [(11)C] carfentanil (μ-OR selective) during neutral and sadness states. With a simple regression model in SPM2 (Wellcome Trust, London, England) we identified brain regions where baseline μ-OR availability (nondisplaceable binding potential [BP(ND)]) and sadness-induced changes in μ-OR BP(ND) were associated with baseline IL-18.
  
  
  RESULTS
  Baseline IL-18 was greater in MDDs than control subjects [t(25) = 2.13, p = .04]. In control subjects IL-18 was correlated with negative emotional ratings at baseline and during sadness induction. In MDDs, IL-18 was positively correlated with baseline regional μ-OR BP(ND) and with sadness-induced μ-opioid system activation in the subgenual anterior cingulate, ventral basal ganglia, and amygdala.
  
  
  CONCLUSIONS
  This study links plasma IL-18 with sadness-induced emotional responses in healthy subjects, the diagnosis of MDD, and μ-opioid functioning, itself involved in stress adaptation, emotion regulation, and reward. This suggests that IL-18 represents a marker associated with emotion regulation/dysregulation at least in part through central opioid mechanisms.
authors.affiliation: Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan 48109-2700, USA. prossin@med.umich.edu
authors.forename: Alan R
authors.initials: AR
authors.lastname: Prossin
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Campbell
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.forename: Steven S
authors.initials: SS
authors.lastname: Zalcman
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D004644:Emotions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D011877:Radionuclide Imaging; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012044:Regression Analysis; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D020382:Interleukin-18; D017450:Receptors, Opioid, mu