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.
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 bipolarpatients receiving lithium therapy were recruited for assessment of TNF-α level. The ALDAlithium response scale (LRS) was used to evaluate longitudinal lithium response in bipolarpatients, 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 bipolarpatients may be productive.
Authors: Azmeraw T Amare; Klaus Oliver Schubert; Liping Hou; Scott R Clark; Sergi Papiol; Urs Heilbronner; Franziska Degenhardt; Fasil Tekola-Ayele; Yi-Hsiang Hsu; Tatyana Shekhtman; Mazda Adli; Nirmala Akula; Kazufumi Akiyama; Raffaella Ardau; Bárbara Arias; Jean-Michel Aubry; Lena Backlund; Abesh Kumar Bhattacharjee; Frank Bellivier; Antonio Benabarre; Susanne Bengesser; Joanna M Biernacka; Armin Birner; Clara Brichant-Petitjean; Pablo Cervantes; Hsi-Chung Chen; Caterina Chillotti; Sven Cichon; Cristiana Cruceanu; Piotr M Czerski; Nina Dalkner; Alexandre Dayer; Maria Del Zompo; J Raymond DePaulo; Bruno Étain; Peter Falkai; Andreas J Forstner; Louise Frisen; Mark A Frye; Janice M Fullerton; Sébastien Gard; Julie S Garnham; Fernando S Goes; Maria Grigoroiu-Serbanescu; Paul Grof; Ryota Hashimoto; Joanna Hauser; Stefan Herms; Per Hoffmann; Andrea Hofmann; Stephane Jamain; Esther Jiménez; Jean-Pierre Kahn; Layla Kassem; Po-Hsiu Kuo; Tadafumi Kato; John Kelsoe; Sarah Kittel-Schneider; Sebastian Kliwicki; Barbara König; Ichiro Kusumi; Gonzalo Laje; Mikael Landén; Catharina Lavebratt; Marion Leboyer; Susan G Leckband; Alfonso Tortorella; Mirko Manchia; Lina Martinsson; Michael J McCarthy; Susan McElroy; Francesc Colom; Marina Mitjans; Francis M Mondimore; Palmiero Monteleone; Caroline M Nievergelt; Markus M Nöthen; Tomas Novák; Claire O'Donovan; Norio Ozaki; Urban Ösby; Andrea Pfennig; James B Potash; Andreas Reif; Eva Reininghaus; Guy A Rouleau; Janusz K Rybakowski; Martin Schalling; Peter R Schofield; Barbara W Schweizer; Giovanni Severino; Paul D Shilling; Katzutaka Shimoda; Christian Simhandl; Claire M Slaney; Alessio Squassina; Thomas Stamm; Pavla Stopkova; Mario Maj; Gustavo Turecki; Eduard Vieta; Julia Volkert; Stephanie Witt; Adam Wright; Peter P Zandi; Philip B Mitchell; Michael Bauer; Martin Alda; Marcella Rietschel; Francis J McMahon; Thomas G Schulze; Bernhard T Baune Journal: JAMA Psychiatry Date: 2018-01-01 Impact factor: 21.596
Authors: Jonathan L Hess; Daniel S Tylee; Rahul Barve; Simone de Jong; Roel A Ophoff; Nishantha Kumarasinghe; Paul Tooney; Ulrich Schall; Erin Gardiner; Natalie Jane Beveridge; Rodney J Scott; Surangi Yasawardene; Antionette Perera; Jayan Mendis; Vaughan Carr; Brian Kelly; Murray Cairns; Ming T Tsuang; Stephen J Glatt Journal: Schizophr Res Date: 2019-08-04 Impact factor: 4.939
Authors: Orestes V Forlenza; Artur Martins Novaes Coutinho; Ivan Aprahamian; Silvana Prando; Luciana Lucas Mendes; Breno S Diniz; Wagner F Gattaz; Carlos A Buchpiguel Journal: ACS Chem Neurosci Date: 2014-04-29 Impact factor: 4.418