title: Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study.
abstract: BACKGROUND
  The DSM-5 encompasses a wide range of symptoms for Major Depressive Disorder (MDD). Symptoms are commonly added up to sum-scores, and thresholds differentiate between healthy and depressed individuals. The underlying assumption is that all patients diagnosed with MDD have a similar condition, and that sum-scores accurately reflect the severity of this condition. To test this assumption, we examined the number of DSM-5 depression symptom patterns in the "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) study.
  
  
  METHODS
  We investigated the number of unique symptom profiles reported by 3703 depressed outpatients at the beginning of the first treatment stage of STAR*D.
  
  
  RESULTS
  Overall, we identified 1030 unique symptom profiles. Of these profiles, 864 profiles (83.9%) were endorsed by five or fewer subjects, and 501 profiles (48.6%) were endorsed by only one individual. The most common symptom profile exhibited a frequency of only 1.8%. Controlling for overall depression severity did not reduce the amount of observed heterogeneity.
  
  
  CONCLUSIONS
  Symptoms were dichotomized to construct symptom profiles. Many subjects enrolled in STAR*D reported medical conditions for which prescribed medications may have affected symptom presentation.
  
  
  CONCLUSIONS
  The substantial symptom variation among individuals who all qualify for one diagnosis calls into question the status of MDD as a specific consistent syndrome and offers a potential explanation for the difficulty in documenting treatment efficacy. We suggest that the analysis of individual symptoms, their patterns, and their causal associations will provide insights that could not be discovered in studies relying on only sum-scores.
authors.affiliation: University of Leuven, Faculty of Psychology and Educational Sciences, Research Group of Quantitative Psychology and Individual Differences, Tiensestraat 102, 3000 Leuven, Belgium. Electronic address: Eiko.Fried@gmail.com.
authors.forename: Eiko I
authors.initials: EI
authors.lastname: Fried
authors.affiliation: Arizona State University, The Center for Evolution & Medicine, Tempe, AZ, USA.
authors.forename: Randolph M
authors.initials: RM
authors.lastname: Nesse
mesh_terms: D000328:Adult; D003863:Depression / Q000523:psychology*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000523:psychology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012720:Severity of Illness Index; D016896:Treatment Outcome
keywords: DSM; Depression symptoms; Heterogeneity; Major depressive disorder; STAR*D