title: Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission.
abstract: OBJECTIVE
  A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission.
  
  
  METHODS
  Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL-1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission.
  
  
  RESULTS
  In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode.
  
  
  CONCLUSIONS
  Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels.
authors.affiliation: Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Shang-Ying
authors.initials: SY
authors.lastname: Tsai
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Chung
authors.forename: Shou-Hung
authors.initials: SH
authors.lastname: Huang
authors.forename: Pao-Huan
authors.initials: PH
authors.lastname: Chen
authors.forename: Hsin-Chien
authors.initials: HC
authors.lastname: Lee
authors.forename: Chian-Jue
authors.initials: CJ
authors.lastname: Kuo
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood* / Q000150:complications*; D001835:Body Weight / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008297:Male; D011569:Psychiatric Status Rating Scales; D012008:Recurrence; D012907:Smoking / Q000097:blood; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D016207:Cytokines; D007328:Insulin; D020738:Leptin; D002097:C-Reactive Protein
keywords: bipolar depression; high-sensitivity C-reactive protein (hs-CRP); inflammation; interleukin-1 receptor antagonist (IL-1Ra); sIL-6R; soluble interleukin-2 receptor (sIL-2R); soluble tumor necrosis factor receptor 1 (sTNF-R1)