title: Evidence for an association between tumor necrosis factor-alpha levels and lithium response.
abstract: BACKGROUND
  The role of inflammation in bipolar disorder has recently emerged as a potential pathophysiological mechanism. Tumor necrosis factor-alpha (TNF-α) modulation may represent a pathogenic molecular target and a biomarker for staging bipolar disorder. In this context, the possible association between lithium response and TNF-α level was examined.
  
  
  METHODS
  Sixty euthymic bipolar patients receiving lithium therapy were recruited for assessment of TNF-α level. The ALDA lithium response scale (LRS) was used to evaluate longitudinal lithium response in bipolar patients, using cut-offs of poor response, partial response and good response. TNF-α level was assessed using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  There was a significant increase in TNF-α level in patients with poor lithium response compared to those with good response, also after controlling for a range of potential confounders (adjusted effect size: 0.47, p=0.011). Partial response showed a directionally similar, but attenuated and statistically inconclusive association (adjusted effect size: 0.16, p=0.326).
  
  
  CONCLUSIONS
  Assessment of response was retrospective and natural course cannot be separated easily from treatment response in an observational design. Selection of additional inflammatory markers could provide for a better understanding of underlying immune changes.
  
  
  CONCLUSIONS
  This study strengthens the hypothesis that TNF-α level may mark or mediate lithium response, and that continuous immune imbalance in poor lithium responders may occasion treatment resistance. Further investigation of immune alterations in treatment-resistant bipolar patients may be productive.
authors: Department of Psychiatry and Psychology, Maastricht University Medical Centre, EURON, Maastricht, The Netherlands. sguloksuz@yahoo.com
authors: Sinan
authors: S
authors: Guloksuz
authors: Kursat
authors: K
authors: Altinbas
authors: Esin
authors: E
authors: Aktas Cetin
authors: Gunter
authors: G
authors: Kenis
authors: Sema
authors: S
authors: Bilgic Gazioglu
authors: Gunnur
authors: G
authors: Deniz
authors: E Timucin
authors: ET
authors: Oral
authors: Jim
authors: J
authors: van Os
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015986:Confounding Factors, Epidemiologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015415:Biomarkers; D018020:Lithium Compounds; D014409:Tumor Necrosis Factor-alpha