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An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes

Lookup NU author(s): Emeritus Professor Jan Scott


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© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives: The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods: We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results: The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions: This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies.

Publication metadata

Author(s): Scott J, Etain B, Manchia M, Brichant-Petitjean C, Geoffroy PA, Schulze T, Alda M, Bellivier F, Amare A, Ardau R, Backlund L, Baune B, Barboza A, Benabarre A, Chaumette B, Chen H, Chillotti C, Clark S, Colom F, Del Zompo M, Dalkner N, Dantas C, Ferentinos P, Garnham J, Jamain S, Jimenez E, Khan J-P, Kuo P, Lavebratt C, Maj M, Millischer V, Monteleone P, Pisanu C, Potash J, Reif A, Reininghaus E, Schalling M, Schofield P, Schubert K, Severino G, Slaney C, Smith D, Squassina A, Tondo L, Vieta E, Witt S

Publication type: Article

Publication status: Published

Journal: Bipolar Disorders

Year: 2020

Volume: 22

Issue: 3

Pages: 255-265

Print publication date: 01/05/2020

Online publication date: 29/08/2019

Acceptance date: 29/08/2019

ISSN (print): 1398-5647

ISSN (electronic): 1399-5618

Publisher: John Wiley & Sons Ltd


DOI: 10.1111/bdi.12829

PubMed id: 31466131


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