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

Mirko Manchia 1 Mazda Adli 2 Nirmala Akula 3 Raffaella Ardau 4 Jean-Michel Aubry 5 Lena Backlund 6 Claudio Banzato 7 Bernhard Baune 8 Frank Bellivier 9 Susanne Bengesser 10 Joanna Biernacka 11 Clara Brichant-Petitjean 9 Elise Bui 3 Cynthia Calkin 1 Andrew Tai Ann Cheng 12 Caterina Chillotti 4 Sven Cichon 13 Scott Clark 8 Piotr Czerski 14 Clarissa Dantas 7 Maria Del Zompo 4, 15 J Raymond Depaulo 16 Sevilla Detera-Wadleigh 3 Bruno Etain 17 Peter Falkai 18 Louise Frisén 6 Mark Frye 11 Jan Fullerton 19 Sébastien Gard 20 Julie Garnham 1 Fernando Goes 16 Paul Grof 21, 22 Oliver Gruber 23 Ryota Hashimoto 24 Joanna Hauser 14 Urs Heilbronner 23 Rebecca Hoban 25, 26 Liping Hou 3 Stéphane Jamain 17 Jean-Pierre Kahn 27 Layla Kassem 3 Tadafumi Kato 28 John Kelsoe 25, 26 Sarah Kittel-Schneider 29 Sebastian Kliwicki 30 Po-Hsiu Kuo 31 Ichiro Kusumi 32, 28 Gonzalo Laje 3 Catharina Lavebratt 33, 34 Marion Leboyer 17 Susan Leckband 25, 35, 36 Carlos López Jaramillo 37 Mario Maj 38 Alain Malafosse 5 Lina Martinsson 6 Takuya Masui 32 Philip Mitchell 39 Frank Mondimore 16 Palmiero Monteleone 38 Audrey Nallet 5 Maria Neuner 29 Tomás Novák 40 Claire O'Donovan 1 Urban Osby 33, 34 Norio Ozaki 41, 42 Roy Perlis 43 Andrea Pfennig 44 James Potash 16, 45 Daniela Reich-Erkelenz 23 Andreas Reif 29 Eva Reininghaus 10 Sara Richardson 3 Guy Rouleau 46, 47 Janusz Rybakowski 30 Martin Schalling 33, 34 Peter Schofield 19 Oliver Schubert 8 Barbara Schweizer 16 Florian Seemüller 18 Maria Grigoroiu-Serbanescu 48 Giovanni Severino 15 Lisa Seymour 11 Claire Slaney 1 Jordan Smoller 43 Alessio Squassina 15 Thomas Stamm 2 Jo Steele 3 Pavla Stopkova 40 Sarah Tighe 16 Alfonso Tortorella 38 Gustavo Turecki 49 Naomi Wray 50 Adam Wright 39 Peter Zandi 51 David Zilles 23 Michael Bauer 44 Marcella Rietschel 52 Francis Mcmahon 3 Thomas Schulze 3, 16, 23, 52, * Martin Alda 1, *
* Auteur correspondant
Abstract : 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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PLoS ONE, Public Library of Science, 2013, 8 (6), pp.e65636. 〈10.1371/journal.pone.0065636〉
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Mirko Manchia, Mazda Adli, Nirmala Akula, Raffaella Ardau, Jean-Michel Aubry, et al.. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report.. PLoS ONE, Public Library of Science, 2013, 8 (6), pp.e65636. 〈10.1371/journal.pone.0065636〉. 〈inserm-00864640〉

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