title: Inflammatory markers and their relationships with leptin and insulin from acute mania to full remission in bipolar disorder.
abstract: BACKGROUND
  Weight gain and increased production of leptin may be associated with immuno-modulation and insulin resistance in bipolar disorder. The links among inflammatory markers, leptin, and insulin of bipolar patients from acute mania to full remission remain unclear.
  
  
  METHODS
  Thirty-three healthy, bipolar I patients under 45 years of age were enrolled. We measured the circulating levels of high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin-1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF-R1]), leptin, and insulin during acute mania and subsequent partial and full remission. The results were compared with 33 age- and gender-matched healthy subjects.
  
  
  RESULTS
  The levels of IL-1Ra and hs-CRP of bipolar patients in both acute mania and partial remission were significantly higher than their levels of control subjects. The hs-CRP level of bipolar patients was also elevated in full remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was independent of each other. They were also independent of the body mass index (BMI) and levels of leptin and insulin measurements. The levels of leptin were all positively associated with insulin levels in the normal subjects and bipolar patients in three phases. However, a significant relationship between leptin and immunoparameter was only seen in full remission with sTNF-R1 (r=0.51). Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=-0.37, p<0.05) during partly remission, and while levels of IL-1Ra tended to normalize when patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend.
  
  
  CONCLUSIONS
  Activated inflammation was found in acute mania, as evidenced by high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more tightly linked to insulin than the immunomodulators. Chronic inflammation may exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP levels in acute mania and persistent higher hs-CRP in full remission.
authors.affiliation: Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan; Department of Psychiatry, Po-Jen General Hospital, Taipei, Taiwan. Electronic address: tmcpsyts@tmu.edu.tw.
authors.forename: Shang-Ying
authors.initials: SY
authors.lastname: Tsai
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: Kuo-Hsuan
authors.initials: KH
authors.lastname: Chung
authors.affiliation: Department of Biochemistry, School of Medicine, Taipei Medical University, Taiwan.
authors.forename: Jui-Yu
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Chian-Jue
authors.initials: CJ
authors.lastname: Kuo
authors.affiliation: Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsin-Chien
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Shou-Hung
authors.initials: SH
authors.lastname: Huang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000276:immunology*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007328:Insulin / Q000097:blood / Q000276:immunology*; D007333:Insulin Resistance / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D020738:Leptin / Q000097:blood / Q000276:immunology*; D008297:Male; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D012074:Remission Induction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D020738:Leptin; D047888:Receptors, Tumor Necrosis Factor, Type I; D002097:C-Reactive Protein