Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report.

Mirko Manchia Mazda Adli Nirmala Akula Raffaella Ardau Jean-Michel Aubry Lena Backlund Claudio Em Banzato Bernhard T Baune Frank Bellivier Susanne Bengesser Joanna M Biernacka Clara Brichant-Petitjean Elise Bui Cynthia V Calkin Andrew Tai Ann Cheng Caterina Chillotti Sven Cichon Scott Clark Piotr M Czerski Clarissa Dantas Maria Del Zompo J Raymond Depaulo Sevilla D Detera-Wadleigh Bruno Etain Peter Falkai Louise Frisén Mark A Frye Jan Fullerton Sébastien Gard Julie Garnham Fernando S Goes Paul Grof Oliver Gruber Ryota Hashimoto Joanna Hauser Urs Heilbronner Rebecca Hoban Liping Hou Stéphane Jamain Jean-Pierre Kahn Layla Kassem Tadafumi Kato John R Kelsoe Sarah Kittel-Schneider Sebastian Kliwicki Po-Hsiu Kuo Ichiro Kusumi Gonzalo Laje Catharina Lavebratt Marion Leboyer Susan G Leckband Carlos A López Jaramillo Mario Maj Alain Malafosse Lina Martinsson Takuya Masui Philip B Mitchell Frank Mondimore Palmiero Monteleone Audrey Nallet Maria Neuner Tomás Novák Claire O'Donovan Urban Osby Norio Ozaki Roy H Perlis Andrea Pfennig James B Potash Daniela Reich-Erkelenz Andreas Reif Eva Reininghaus Sara Richardson Guy A Rouleau Janusz K Rybakowski Martin Schalling Peter R Schofield Oliver K Schubert Barbara Schweizer Florian Seemüller Maria Grigoroiu-Serbanescu Giovanni Severino Lisa R Seymour Claire Slaney Jordan W Smoller Alessio Squassina Thomas Stamm Jo Steele Pavla Stopkova Sarah K Tighe Alfonso Tortorella Gustavo Turecki Naomi R Wray Adam Wright Peter P Zandi David Zilles Michael Bauer Marcella Rietschel Francis J McMahon Thomas G Schulze Martin Alda

PLoS One 2013 19;8(6):e65636. Epub 2013 Jun 19.

Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.

Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.

Materials And Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.

Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders).

Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

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October 2017
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