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 E.M. 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 Ösby; 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

doi:10.1371/journal.pone.0065636

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 E.M. 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 DantasMaria 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 Ösby, 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

School of Medicine

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93 Scopus citations

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.

Original language	English (US)
Article number	e65636
Journal	PloS one
Volume	8
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0065636
State	Published - Jun 19 2013

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Manchia, M., Adli, M., Akula, N., Ardau, R., Aubry, J. M., Backlund, L., Banzato, C. E. M., Baune, B. T., Bellivier, F., Bengesser, S., Biernacka, J. M., Brichant-Petitjean, C., Bui, E., Calkin, C. V., Cheng, A. T. A., Chillotti, C., Cichon, S., Clark, S., Czerski, P. M., ... Alda, M. (2013). Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report. PloS one, 8(6), Article e65636. https://doi.org/10.1371/journal.pone.0065636

Manchia, M, Adli, M, Akula, N, Ardau, R, Aubry, JM, Backlund, L, Banzato, CEM, Baune, BT, Bellivier, F, Bengesser, S, Biernacka, JM, Brichant-Petitjean, C, Bui, E, Calkin, CV, Cheng, ATA, Chillotti, C, Cichon, S, Clark, S, Czerski, PM, Dantas, C, Del Zompo, M, 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, Ösby, 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 2013, 'Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report', PloS one, vol. 8, no. 6, e65636. https://doi.org/10.1371/journal.pone.0065636

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title = "Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report",

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.",

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

year = "2013",

month = jun,

day = "19",

doi = "10.1371/journal.pone.0065636",

language = "English (US)",

volume = "8",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "6",

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TY - JOUR

T1 - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder

T2 - A Consortium on Lithium Genetics (ConLiGen) Report

AU - Manchia, Mirko

AU - Adli, Mazda

AU - Akula, Nirmala

AU - Ardau, Raffaella

AU - Aubry, Jean Michel

AU - Backlund, Lena

AU - Banzato, Claudio E.M.

AU - Baune, Bernhard T.

AU - Bellivier, Frank

AU - Bengesser, Susanne

AU - Biernacka, Joanna M.

AU - Brichant-Petitjean, Clara

AU - Bui, Elise

AU - Calkin, Cynthia V.

AU - Cheng, Andrew Tai Ann

AU - Chillotti, Caterina

AU - Cichon, Sven

AU - Clark, Scott

AU - Czerski, Piotr M.

AU - Dantas, Clarissa

AU - Del Zompo, Maria

AU - DePaulo, J. Raymond

AU - Detera-Wadleigh, Sevilla D.

AU - Etain, Bruno

AU - Falkai, Peter

AU - Frisén, Louise

AU - Frye, Mark A.

AU - Fullerton, Jan

AU - Gard, Sébastien

AU - Garnham, Julie

AU - Goes, Fernando S.

AU - Grof, Paul

AU - Gruber, Oliver

AU - Hashimoto, Ryota

AU - Hauser, Joanna

AU - Heilbronner, Urs

AU - Hoban, Rebecca

AU - Hou, Liping

AU - Jamain, Stéphane

AU - Kahn, Jean Pierre

AU - Kassem, Layla

AU - Kato, Tadafumi

AU - Kelsoe, John R.

AU - Kittel-Schneider, Sarah

AU - Kliwicki, Sebastian

AU - Kuo, Po Hsiu

AU - Kusumi, Ichiro

AU - Laje, Gonzalo

AU - Lavebratt, Catharina

AU - Leboyer, Marion

AU - Leckband, Susan G.

AU - López Jaramillo, Carlos A.

AU - Maj, Mario

AU - Malafosse, Alain

AU - Martinsson, Lina

AU - Masui, Takuya

AU - Mitchell, Philip B.

AU - Mondimore, Frank

AU - Monteleone, Palmiero

AU - Nallet, Audrey

AU - Neuner, Maria

AU - Novák, Tomás

AU - O'Donovan, Claire

AU - Ösby, Urban

AU - Ozaki, Norio

AU - Perlis, Roy H.

AU - Pfennig, Andrea

AU - Potash, James B.

AU - Reich-Erkelenz, Daniela

AU - Reif, Andreas

AU - Reininghaus, Eva

AU - Richardson, Sara

AU - Rouleau, Guy A.

AU - Rybakowski, Janusz K.

AU - Schalling, Martin

AU - Schofield, Peter R.

AU - Schubert, Oliver K.

AU - Schweizer, Barbara

AU - Seemüller, Florian

AU - Grigoroiu-Serbanescu, Maria

AU - Severino, Giovanni

AU - Seymour, Lisa R.

AU - Slaney, Claire

AU - Smoller, Jordan W.

AU - Squassina, Alessio

AU - Stamm, Thomas

AU - Steele, Jo

AU - Stopkova, Pavla

AU - Tighe, Sarah K.

AU - Tortorella, Alfonso

AU - Turecki, Gustavo

AU - Wray, Naomi R.

AU - Wright, Adam

AU - Zandi, Peter P.

AU - Zilles, David

AU - Bauer, Michael

AU - Rietschel, Marcella

AU - McMahon, Francis J.

AU - Schulze, Thomas G.

AU - Alda, Martin

PY - 2013/6/19

Y1 - 2013/6/19

N2 - 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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84879219224&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0065636

DO - 10.1371/journal.pone.0065636

M3 - Article

C2 - 23840348

AN - SCOPUS:84879219224

SN - 1932-6203

VL - 8

JO - PloS one

JF - PloS one

IS - 6

M1 - e65636

ER -

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

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