title: Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/depressive states of bipolar disorder.
abstract: OBJECTIVE
  Inflammatory cytokines have been suggested to be the trait or state markers of bipolar disorder, but with inconsistent results. This may be related to small sample sizes and poor control of some important confounding factors.
  
  
  METHODS
  Gender/age-matched outpatients with bipolar disorder and normal controls were enrolled. The clinical symptoms were rated using the Montgomery Åsberg Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1), soluble P-selectin receptor (sP-selectin), and monocyte chemotactic protein-1 (MCP-1), were assessed by enzyme-linked immunosorbent assays.
  
  
  RESULTS
  In total, 130 patients with bipolar disorder and 130 normal subjects were enrolled. Among the patients with bipolar disorder, 77 (59.2%) had bipolar I disorder, 53 (40.8%) had bipolar II disorder; 75 (57.7%) were in a euthymic state, 14 (10.8%) were in a manic/hypomanic state, and 41 (31.5%) were in a depressive state. The 130 bipolar patients had significantly higher levels of all cytokines than the normal controls (all p<0.0001). Using multivariate regression analysis with controlling of age, gender, BMI, smoking, duration of illness, and medication grouping, the patients with bipolar II disorder had significantly lower levels of sTNF-R1 than the patients with bipolar I disorder (p=0.038); the patients in a depressive state had significantly lower levels of sTNF-R1 than the patients in manic/hypomanic and euthymic states (p=0.009).
  
  
  CONCLUSIONS
  The study supported the association of bipolar disorder with inflammatory dysregulation, and sTNF-R1 may be a potential biomarker for staging bipolar disorder.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: ymbi@mail2000.com.tw.
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tung-Ping
authors.initials: TP
authors.lastname: Su
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan; Institute of Life Science, National Taitung University, Taitung, Taiwan; Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chiou
authors.initials: C
authors.lastname: Wen-Fei
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tu
authors.initials: T
authors.lastname: Pei-Chi
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chen
authors.initials: C
authors.lastname: Mu-Hong
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000523:psychology*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D019007:P-Selectin / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D019007:P-Selectin; D015375:Receptors, Interleukin-2; D019947:Receptors, Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D002097:C-Reactive Protein
keywords: Bipolar disorder; Inflammatory cytokines