Evidence for an association between tumor necrosis factor-alpha levels and lithium response


Guloksuz S., ALTINBAS K., Cetin E. A., Kenis G., Gazioglu S., Deniz G., ...More

JOURNAL OF AFFECTIVE DISORDERS, no.1-3, pp.148-152, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2012
  • Doi Number: 10.1016/j.jad.2012.04.044
  • Journal Name: JOURNAL OF AFFECTIVE DISORDERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus
  • Page Numbers: pp.148-152
  • Keywords: Bipolar disorder, Tumor necrosis factor, Lithium, Cytokine, Inflammation, Treatment, BIPOLAR AFFECTIVE-DISORDER, TNF-ALPHA, IMBALANCE, IL-6
  • Istanbul University Affiliated: Yes

Abstract

Background: The role of inflammation in bipolar disorder has recently emerged as a potential pathophysiological mechanism. Tumor necrosis factor-alpha (TNIF-alpha) 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-alpha level was examined. Methods: Sixty euthymic bipolar patients receiving lithium therapy were recruited for assessment of TNF-alpha. 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-alpha level was assessed using enzyme-linked immunosorbent assay. Results: There was a significant increase in TNF-alpha 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). Limitations: 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-alpha 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. (C) 2012 Elsevier B.V. All rights reserved.