title: The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study.
abstract: OBJECTIVE
  We examined the relationship between biological rhythms and severity of depressive symptoms in subjects with bipolar disorder and the effects of biological rhythms alterations on functional impairment.
  
  
  METHODS
  Bipolar patients (n = 260) and healthy controls (n = 191) were recruited from mood disorders programs in three sites (Spain, Brazil, and Canada). Parameters of biological rhythms were measured using the Biological Rhythms Assessment in Neuropsychiatry (BRIAN), an interviewer administered questionnaire that assesses disruptions in sleep, eating patterns, social rhythms, and general activity.
  
  
  RESULTS
  Multivariate analyses of covariance showed significant intergroup differences after controlling for potential confounders (Pillai's F = 49.367; df = 2, P < 0.001). Depressed patients had the greatest biological rhythms disturbance, followed by patients with subsyndromal symptoms, euthymic patients, and healthy controls. Biological rhythms and HAMD scores were independent predictors of poor functioning (F = 12.841, df = 6, P < 0.001, R2= 0.443).
  
  
  CONCLUSIONS
  Our study shows a dose-dependent association between the severity of depressive symptoms and degree of biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning.
authors.affiliation: Laboratory of Molecular Psychiatry, INCT for Translational Medicine - CNPq, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Post Graduate Program in Medicine, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Pinho
authors.affiliation: MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Sehmbi
authors.affiliation: Mood Disorders Program, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
authors.forename: L E
authors.initials: LE
authors.lastname: Cudney
authors.affiliation: Laboratory of Molecular Psychiatry, INCT for Translational Medicine - CNPq, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Post Graduate Program in Medicine, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Kauer-Sant'anna
authors.affiliation: Laboratory of Molecular Psychiatry, INCT for Translational Medicine - CNPq, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Post Graduate Program in Medicine, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: P V
authors.initials: PV
authors.lastname: Magalhães
authors.affiliation: Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Reinares
authors.affiliation: Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: C M
authors.initials: CM
authors.lastname: Bonnín
authors.affiliation: MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.|Mood Disorders Program, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.|Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
authors.forename: R B
authors.initials: RB
authors.lastname: Sassi
authors.affiliation: Laboratory of Molecular Psychiatry, INCT for Translational Medicine - CNPq, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Post Graduate Program in Medicine, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Colom
authors.affiliation: Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vieta
authors.affiliation: MiNDS Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.|Mood Disorders Program, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.|Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
authors.forename: B N
authors.initials: BN
authors.lastname: Frey
authors.affiliation: Laboratory of Molecular Psychiatry, INCT for Translational Medicine - CNPq, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Post Graduate Program in Medicine, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Rosa
keywords: biological rhythm; bipolar disorder; circadian rhythm; depression; functioning