title: Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder - Results from a prospective study.
abstract: BACKGROUND
  Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression.
  
  
  OBJECTIVE
  To investigate whether neutrophins and inflammatory marker vary with mood states and are increased in patients with bipolar disorder type I during euthymia as well as in all affective states as a group, compared to levels in healthy control subjects.
  
  
  METHODS
  In a prospective 6-12 months follow-up study, we investigated state specific, intra-individual alterations in levels of BDNF, hsCRP, IL-1β, IL-6, IL-8, IL-18 and TNF-α in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic and depressive and manic states and compared with repeated measurements in healthy control subjects. Data were analysed with linear mixed effects model and with adjustment for gender, age, BMI, alcohol intake and smoking.
  
  
  RESULTS
  From inclusion to end of the 6-12 months follow-up, samples of blood were drawn from the 60 patients during a total of 180 affective states, comprising 57 manic, 11 mixed, 23 depressive and 89 states of euthymia. Further, 69 blood samples were drawn from 35 healthy control subjects with three months apart. In unadjusted mixed-model analysis, levels of IL-6 and IL-8 were increased 64% (b=1.64, 95% CI: 1.31-2.05, p=<0.0001) and 24% (b=1.24, 95% CI: 1.05-1.47, p=0.013), respectively in patients with bipolar disorder overall compared with healthy control subjects. However, in adjusted models, no statistically significant differences were found in any measure between patients and control individuals. Levels of hsCRP in depressive states were decreased with 40% (95% CI: 5-62%, p=0.029) compared with euthymia and with 48% (95% CI: 17-66%, p=0.006) when compared with hypomanic/manic states after adjustment. BDNF and the other inflammatory markers did not vary according to affective state in adjusted mixed models.
  
  
  CONCLUSIONS
  Patients were all medicated, specifically with high doses of atypical antipsychotics during the manic index episodes.
  
  
  CONCLUSIONS
  In a sample recruited during hospitalization for acute mania, levels of hsCRP varied according to affective state with higher levels during manic states compared with depressive states.
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Jacoby
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Munkholm
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: The Centre of Inflammation and Metabolism and The Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
authors.affiliation: Psychiatric Center Copenhagen, Rigshospitalet, and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: lars.vedel.kessing@regionh.dk.
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000523:psychology; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D003863:Depression / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012907:Smoking / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Bipolar disorder; Brain-derived neurotrophic factor; CRP; Cytokines; Mania