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

Manchia M, 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, Zompo MD, 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 G, Seymour LR, Slaney C, Smoller JW, Squassina A, 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 - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

Distribution of total and A scores in the Consortium on Lithium Genetics sample.Histogram plot of the scale scores in 1,308 bipolar disorder patients characterized for response to lithium maintenance treatment.
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pone-0065636-g001: Distribution of total and A scores in the Consortium on Lithium Genetics sample.Histogram plot of the scale scores in 1,308 bipolar disorder patients characterized for response to lithium maintenance treatment.

Mentions: Figure 1 illustrates the distribution of TS and A score in 1,308 BD patients characterized for lithium response. Two hundred eighty three patients (21.6%) had TS equal to 0 and 104 patients (8%) had A score equal to 0. In the whole sample the mean A score ± standard deviation] was 6.1±3.1 and the mean TS was 4.4±3.1. The joint distribution of TS and A scores is represented in Figure 2. It illustrates the presence of two frequency peaks at the extreme ends of the scale, namely at 0 and in the area comprised between score A equal to 9 and TS equal to 8–10. A third peak is present at the intersection of A score equal to 6 and TS of 4.


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

Manchia M, 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, Zompo MD, 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 G, Seymour LR, Slaney C, Smoller JW, Squassina A, 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 - PLoS ONE (2013)

Distribution of total and A scores in the Consortium on Lithium Genetics sample.Histogram plot of the scale scores in 1,308 bipolar disorder patients characterized for response to lithium maintenance treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3686769&req=5

pone-0065636-g001: Distribution of total and A scores in the Consortium on Lithium Genetics sample.Histogram plot of the scale scores in 1,308 bipolar disorder patients characterized for response to lithium maintenance treatment.
Mentions: Figure 1 illustrates the distribution of TS and A score in 1,308 BD patients characterized for lithium response. Two hundred eighty three patients (21.6%) had TS equal to 0 and 104 patients (8%) had A score equal to 0. In the whole sample the mean A score ± standard deviation] was 6.1±3.1 and the mean TS was 4.4±3.1. The joint distribution of TS and A scores is represented in Figure 2. It illustrates the presence of two frequency peaks at the extreme ends of the scale, namely at 0 and in the area comprised between score A equal to 9 and TS equal to 8–10. A third peak is present at the intersection of A score equal to 6 and TS of 4.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus