双相情感障碍中锂盐维持治疗反应的评估：锂盐遗传学联盟（ConLiGen）报告
Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report.
作者信息
Manchia Mirko, Adli Mazda, Akula Nirmala, Ardau Raffaella, Aubry Jean-Michel, Backlund Lena, Banzato Claudio Em, Baune Bernhard T, Bellivier Frank, Bengesser Susanne, Biernacka Joanna M, Brichant-Petitjean Clara, Bui Elise, Calkin Cynthia V, Cheng Andrew Tai Ann, Chillotti Caterina, Cichon Sven, Clark Scott, Czerski Piotr M, Dantas Clarissa, Zompo Maria Del, Depaulo J Raymond, Detera-Wadleigh Sevilla D, Etain Bruno, Falkai Peter, Frisén Louise, Frye Mark A, Fullerton Jan, Gard Sébastien, Garnham Julie, Goes Fernando S, Grof Paul, Gruber Oliver, Hashimoto Ryota, Hauser Joanna, Heilbronner Urs, Hoban Rebecca, Hou Liping, Jamain Stéphane, Kahn Jean-Pierre, Kassem Layla, Kato Tadafumi, Kelsoe John R, Kittel-Schneider Sarah, Kliwicki Sebastian, Kuo Po-Hsiu, Kusumi Ichiro, Laje Gonzalo, Lavebratt Catharina, Leboyer Marion, Leckband Susan G, López Jaramillo Carlos A, Maj Mario, Malafosse Alain, Martinsson Lina, Masui Takuya, Mitchell Philip B, Mondimore Frank, Monteleone Palmiero, Nallet Audrey, Neuner Maria, Novák Tomás, O'Donovan Claire, Osby Urban, Ozaki Norio, Perlis Roy H, Pfennig Andrea, Potash James B, Reich-Erkelenz Daniela, Reif Andreas, Reininghaus Eva, Richardson Sara, Rouleau Guy A, Rybakowski Janusz K, Schalling Martin, Schofield Peter R, Schubert Oliver K, Schweizer Barbara, Seemüller Florian, Grigoroiu-Serbanescu Maria, Severino Giovanni, Seymour Lisa R, Slaney Claire, Smoller Jordan W, Squassina Alessio, Stamm Thomas, Steele Jo, Stopkova Pavla, Tighe Sarah K, Tortorella Alfonso, Turecki Gustavo, Wray Naomi R, Wright Adam, Zandi Peter P, Zilles David, Bauer Michael, Rietschel Marcella, McMahon Francis J, Schulze Thomas G, Alda Martin
机构信息
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
出版信息
PLoS One. 2013 Jun 19;8(6):e65636. doi: 10.1371/journal.pone.0065636. Print 2013.
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.
目的
双相情感障碍（BD）锂盐维持治疗反应的评估因治疗时长不一、临床病程不可预测以及依从性常常不一致而变得复杂。文献中已提出评估锂盐反应的前瞻性和回顾性方法。在本研究中，我们报告了锂盐遗传学联盟（ConLiGen）研究目前使用的“双相情感障碍研究对象长期治疗反应回顾性标准”量表的关键表型指标。
材料与方法
29个ConLiGen研究点参与了一个两阶段的病例 vignette 评分程序，以检验锂盐反应的评分者间一致性[卡帕（κ）]和可靠性[组内相关系数（ICC）]。在两个阶段之间，带有注释的第一轮 vignette 和评分指南被分发给专家研究临床医生用于培训目的。此外，我们使用混合模型分析了1308例患者的治疗反应分数的分布特性。
结果
在第一组和第二组 vignette 中，各研究点之间显示出高度和中度的一致性（κ分别为0.66和0.54），培训后无显著改善。然而，将A分数作为定量性状来定义反应，并选择B标准为4或更低的病例，在两个阶段之间显示出改善（ICC1分别为0.71和ICC2为0.75）。分数分布的混合模型表明存在三个亚组（完全反应者、部分反应者、无反应者）。
结论
我们确定了锂盐反应的两种定义，一种是二分法，另一种是连续法，评分者间一致性和可靠性为中度到高度。锂盐反应的准确表型测量对于正在进行的ConLiGen药物基因组学研究至关重要。
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