title: Cross-validation of clinical characteristics and treatment patterns associated with phenotypes for lithium response defined by the Alda scale.
abstract: It is increasingly recognised that reliable and valid assessments of lithium response are needed in order to target more efficiently the use of this medication in bipolar disorders (BD) and to identify genotypes, endophenotypes and biomarkers of response.
  
  
  
  In a large, multi-centre, clinically representative sample of 300 cases of BD, we assess external clinical validators of lithium response phenotypes as defined using three different recommended approaches to scoring the Alda lithium response scale. The scale comprises an A scale (rating lithium response) and a B scale (assessing confounders).
  
  
  
  Analysis of the two continuous scoring methods (A scale score minus the B scale score, or A scale score in those with a low B scale score) demonstrated that 21-23% of the explained variance in lithium response was accounted for by a positive family history of BD I and the early introduction of lithium. Categorical definitions of response suggest poor response is also associated with a positive history of alcohol and/or substance use comorbidities. High B scale scores were significantly associated with longer duration of illness prior to receiving lithium and the presence of psychotic symptoms.
  
  
  
  The original sample was not recruited specifically to study lithium response. The Alda scale is designed to assess response retrospectively.
  
  
  
  This cross-validation study identifies different clinical phenotypes of lithium response when defined by continuous or categorical measures. Future clinical, genetic and biomarker studies should report both the findings and the method employed to assess lithium response according to the Alda scale.
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom; Centre for Affective Disorders, Institute of Psychiatry, London, United Kingdom. Electronic address: jan.scott@newcastle.ac.uk.
authors.forename: Jan
authors.initials: J
authors.lastname: Scott
authors.affiliation: Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France.
authors.forename: Pierre Alexis
authors.initials: PA
authors.lastname: Geoffroy
authors.affiliation: Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sportiche
authors.affiliation: Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France.
authors.forename: Clara
authors.initials: C
authors.lastname: Brichant-Petit-Jean
authors.affiliation: Fondation FondaMental, Créteil 94000, France; Hôpital Charles Perrens, Centre Expert Trouble Bipolaire, Service de Psychiatrie Adulte, Pôle 3-4-7, Bordeaux, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gard
authors.affiliation: Fondation FondaMental, Créteil 94000, France; Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de Brabois, Vandoeuvre Les Nancy, France; Université de Lorraine, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kahn
authors.affiliation: Fondation FondaMental, Créteil 94000, France; Pôle de psychiatrie, Hôpital Sainte Marguerite, Assistance Publique Hôpitaux de Marseille, France; EA 3279-Self-perceived Health Assessment Research Unit, School of Medicine, Timone University, Marseille, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Azorin
authors.affiliation: Institut Pasteur, Unit of Perception and Memory, F-75015 Paris, France; Pôle de Psychiatrie, Hôpital Albert Chenevier, 40 rue de Mesly, 94000 Créteil, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
authors.affiliation: Centre for Affective Disorders, Institute of Psychiatry, London, United Kingdom; Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.affiliation: Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, France; Fondation FondaMental, Créteil 94000, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
mesh_terms: D000328:Adult; D015415:Biomarkers; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D015897:Comorbidity; D005260:Female; D005838:Genotype; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011618:Psychotic Disorders / Q000188:drug therapy; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D018020:Lithium Compounds; D008094:Lithium
keywords: Alda scale; Bipolar disorder; Cross-validation; Lithium; Predictors; Response