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

• Published in: Journal of affective disorders Vol. 143; no. 1; pp. 148 - 152
• Main Authors: Guloksuz, Sinan, Altinbas, Kursat, Aktas Cetin, Esin, Kenis, Gunter, Bilgic Gazioglu, Sema, Deniz, Gunnur, Oral, E. Timucin, van Os, Jim
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 20.12.2012; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Assessment; Biological and medical sciences; Biological markers; Biomarkers - blood; Bipolar affective disorder; Bipolar disorder; Bipolar Disorder - blood; Bipolar Disorder - drug therapy; Bipolar Disorder - immunology; Bipolar disorders; Cell death; Confounding Factors (Epidemiology); Cytokine; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Inflammation - blood; Inflammation - immunology; Lithium; Lithium Compounds - therapeutic use; Male; Medical sciences; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Retrospective Studies; Treatment; Treatment Outcome; Tumor necrosis factor; Tumor Necrosis Factor-alpha - blood; Tumours; Bipolar disorder; Lithium; Inflammation; Treatment; Tumor necrosis factor; Cytokine; Mood disorder; Psychotropic; Mood stabilizer; Tumor necrosis factor α
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2012.04.044

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). 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-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.