title: PSYCHIATRIC COMORBIDITY DOES NOT ONLY DEPEND ON DIAGNOSTIC THRESHOLDS: AN ILLUSTRATION WITH MAJOR DEPRESSIVE DISORDER AND GENERALIZED ANXIETY DISORDER.
abstract: BACKGROUND
  High rates of psychiatric comorbidity are subject of debate: To what extent do they depend on classification choices such as diagnostic thresholds? This paper investigates the influence of different thresholds on rates of comorbidity between major depressive disorder (MDD) and generalized anxiety disorder (GAD).
  
  
  METHODS
  Point prevalence of comorbidity between MDD and GAD was measured in 74,092 subjects from the general population (LifeLines) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria. Comorbidity rates were compared for different thresholds by varying the number of necessary criteria from ≥ 1 to all nine symptoms for MDD, and from ≥ 1 to all seven symptoms for GAD.
  
  
  RESULTS
  According to DSM thresholds, 0.86% had MDD only, 2.96% GAD only, and 1.14% both MDD and GAD (odds ratio (OR) 42.6). Lower thresholds for MDD led to higher rates of comorbidity (1.44% for ≥ 4 of nine MDD symptoms, OR 34.4), whereas lower thresholds for GAD hardly influenced comorbidity (1.16% for ≥ 3 of seven GAD symptoms, OR 38.8). Specific patterns in the distribution of symptoms within the population explained this finding: 37.3% of subjects with core criteria of MDD and GAD reported subthreshold MDD symptoms, whereas only 7.6% reported subthreshold GAD symptoms.
  
  
  CONCLUSIONS
  Lower thresholds for MDD increased comorbidity with GAD, but not vice versa, owing to specific symptom patterns in the population. Generally, comorbidity rates result from both empirical symptom distributions and classification choices and cannot be reduced to either of these exclusively. This insight invites further research into the formation of disease concepts that allow for reliable predictions and targeted therapeutic interventions.
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: van Loo
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schoevers
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.|Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia.|Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: de Jonge
authors.affiliation: Faculty of Philosophy, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Romeijn
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis* / Q000453:epidemiology; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence
keywords: DSM; comorbidity; disease classification; generalized anxiety disorder; major depressive disorder