title: The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity.
abstract: BACKGROUND
  Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question.
  
  
  METHODS
  Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes.
  
  
  RESULTS
  Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6-72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors.
  
  
  CONCLUSIONS
  Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.
authors: Department of Psychiatry,University of Groningen, University Medical Center Groningen,The Netherlands.
authors: K J
authors: KJ
authors: Wardenaar
authors: Department of Psychiatry,University of Groningen, University Medical Center Groningen,The Netherlands.
authors: H M
authors: HM
authors: van Loo
authors: Department of Biostatistics,Harvard School of Public Health,Boston, MA,USA.
authors: T
authors: T
authors: Cai
authors: Department of Psychiatry,MGH Clinical Trials Network and Institute,Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA,USA.
authors: M
authors: M
authors: Fava
authors: Department of Health Care Policy,Harvard Medical School,Boston, MA,USA.
authors: M J
authors: MJ
authors: Gruber
authors: Department of Biostatistics,Harvard School of Public Health,Boston, MA,USA.
authors: J
authors: J
authors: Li
authors: Department of Psychiatry,University of Groningen, University Medical Center Groningen,The Netherlands.
authors: P
authors: P
authors: de Jonge
authors: Depression Clinical and Research Program and the Bipolar Clinic and Research Program,Massachusetts General Hospital and Harvard Medical School,Boston, MA,USA.
authors: A A
authors: AA
authors: Nierenberg
authors: Department of Health Care Policy,Harvard Medical School,Boston, MA,USA.
authors: M V
authors: MV
authors: Petukhova
authors: Department of Health Care Policy,Harvard Medical School,Boston, MA,USA.
authors: S
authors: S
authors: Rose
authors: Department of Health Care Policy,Harvard Medical School,Boston, MA,USA.
authors: N A
authors: NA
authors: Sampson
authors: Department of Psychiatry,University of Groningen, University Medical Center Groningen,The Netherlands.
authors: R A
authors: RA
authors: Schoevers
authors: Johnson & Johnson Pharmaceutical Research and Development,Titusville, NJ,USA.
authors: M A
authors: MA
authors: Wilcox
authors: IMIM-Hospital del Mar Research Institute, Parc de Salut Mar,Pompeu Fabra University (UPF), andCIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona,Spain.
authors: J
authors: J
authors: Alonso
authors: Department of Psychiatry and Behavioral Science, Stony Brook School of Medicine,State University of New York at Stony Brook,Stony Brook, NY,USA.
authors: E J
authors: EJ
authors: Bromet
authors: Psychology Research Institute,University of Ulster,Londonderry,UK.
authors: B
authors: B
authors: Bunting
authors: National School of Public Health,Management and Professional Development, Bucharest,Romania.
authors: S E
authors: SE
authors: Florescu
authors: Department of Public Health,Yamagata University School of Medicine,Japan.
authors: A
authors: A
authors: Fukao
authors: University College Hospital,Ibadan,Nigeria.
authors: O
authors: O
authors: Gureje
authors: Shenzhen Institute of Mental Health and Shenzhen Kangning Hospital,Guangdong Province,People's Republic of China.
authors: C
authors: C
authors: Hu
authors: Institute of Mental Health, Peking University,Beijing,People's Republic of China.
authors: Y Q
authors: YQ
authors: Huang
authors: Department of Psychiatry and Clinical Psychology,St George Hospital University Medical Center,Department of Psychiatry and Clinical Psychology, Faculty of Medicine, Balamand University Medical School, andInstitute for Development Research Advocacy and Applied Care (IDRAAC), Beirut,Lebanon.
authors: A N
authors: AN
authors: Karam
authors: Research and Planning,Mental Health Services,Ministry of Health, Jerusalem,Israel.
authors: D
authors: D
authors: Levinson
authors: National Institute of Psychiatry,Calzada Mexico Xochimilco, Mexico City,Mexico.
authors: M E
authors: ME
authors: Medina Mora
authors: Universidad Colegio Mayor de Cundinamarca,Bogota,Colombia.
authors: J
authors: J
authors: Posada-Villa
authors: Department of Psychological Medicine,University of Otago,Dunedin,New Zealand.
authors: K M
authors: KM
authors: Scott
authors: Mental Health Center-Duhok,Kurdistan Region,Iraq.
authors: N I
authors: NI
authors: Taib
authors: Department of Social Medicine,Federal University of Espirito Santo,Vitoria,Brazil.
authors: M C
authors: MC
authors: Viana
authors: Department of Mental Health,Universidade Nova de Lisboa,Lisbon,Portugal.
authors: M
authors: M
authors: Xavier
authors: National Center of Public Health and Analyses,Department of Mental Health, Sofia,Bulgaria.
authors: Z
authors: Z
authors: Zarkov
authors: Department of Health Care Policy,Harvard Medical School,Boston, MA,USA.
authors: R C
authors: RC
authors: Kessler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001185:Artificial Intelligence; D016000:Cluster Analysis; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000145:classification* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D014943:Global Health / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult