Assessment of response to lithium maintenance treatment in bipolar disorder: A Consortium on Lithium Genetics (ConLiGen) report

MANCHIA, MIRKO;Adli M;Akula N;Ardau R;Aubry JM;Backlund L;Banzato CE;Baune BT;Bellivier F;Bengesser S;Biernacka JM;Brichant Petitjean C;Bui E;Calkin CV;Cheng AT;Chillotti C;Cichon S;Clark S;Czerski PM;Dantas C;DEL ZOMPO, MARIA;Depaulo JR;Detera Wadleigh SD;Etain B;Falkai P;Frisén L;Frye MA;Fullerton J;Gard S;Garnham J;Goes FS;Grof P;Gruber O;Hashimoto R;Hauser J;Heilbronner U;Hoban R;Hou L;Jamain S;Kahn JP;Kassem L;Kato T;Kelsoe JR;Kittel Schneider S;Kliwicki S;Kuo PH;Kusumi I;Laje G;Lavebratt C;Leboyer M;Leckband SG;López Jaramillo CA;Maj M;Malafosse A;Martinsson L;Masui T;Mitchell PB;Mondimore F;Monteleone P;Nallet A;Neuner M;Novák T;O'Donovan C;Osby U;Ozaki N;Perlis RH;Pfennig A;Potash JB;Reich Erkelenz D;Reif A;Reininghaus E;Richardson S;Rouleau GA;Rybakowski JK;Schalling M;Schofield PR;Schubert OK;Schweizer B;Seemüller F;Grigoroiu Serbanescu M;SEVERINO, GIOVANNI;Seymour LR;Slaney C;Smoller JW;SQUASSINA, ALESSIO;Stamm T;Steele J;Stopkova P;Tighe SK;Tortorella A;Turecki G;Wray NR;Wright A;Zandi PP;Zilles D;Bauer M;Rietschel M;McMahon FJ;Schulze TG;Alda M.

2013-01-01

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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.