title: Association of Symptom Network Structure With the Course of [corrected] Depression.
abstract: OBJECTIVE
  Major depressive disorder (MDD) is a heterogeneous condition in terms of symptoms, course, and underlying disease mechanisms. Current classifications do not adequately address this complexity. In novel network approaches to psychopathology, psychiatric disorders are conceptualized as complex dynamic systems of mutually interacting symptoms. This perspective implies that a more densely connected network of symptoms is indicative of a poorer prognosis, but, to date, no previous study has examined whether network structure is indeed associated with the longitudinal course of MDD.
  
  
  OBJECTIVE
  To examine whether the baseline network structure of MDD symptoms is associated with the longitudinal course of MDD.
  
  
  METHODS
  In this prospective study, in which remittent and persistent MDD was defined on the basis of a follow-up assessment after 2 years, 515 patients from the Netherlands Study of Depression and Anxiety with past-year MDD (established with the Composite International Diagnostic Interview) and at least moderate depressive symptoms (assessed with the Inventory of Depressive Symptomatology [IDS]) at baseline were studied. Baseline starting and ending dates were September 1, 2004, through February 28, 2007. Follow-up starting and ending dates were September 1, 2006, through February 28, 2009. Analysis was conducted August 2015. The MDD was considered persistent if patients had at least moderate depressive symptoms (IDS) at 2-year follow-up; otherwise, the MDD was considered remitted.
  
  
  METHODS
  Sparse network structures of baseline MDD symptoms assessed via IDS were computed. Global and local connectivity of network structures were compared across persisters and remitters using a permutation test.
  
  
  RESULTS
  Among the 515 patients, 335 (65.1%) were female, mead (SD) age was 40.9 (12.1) years, and 253 (49.1%) had persistent MDD at 2-year follow-up. Persisters (n = 253) had a higher baseline IDS sum score than remitters (n = 262) (mean [SD] score, 40.2 [8.9] vs 35.1 [7.1]; the test statistic for the difference in IDS sum score was 22 027; P < .001). The test statistic for the difference in network connectivity was 1.79 (P = .01) for the original data, 1.55 for data matched on IDS sum score (P = .04), and 1.65 for partialed out data (P = .02). At the symptom level, fatigue or loss of energy and feeling guilty had the largest difference in importance in persisters' network compared with that of remitters (Cohen d = 1.13 and 1.18, respectively).
  
  
  CONCLUSIONS
  This study reports that symptom networks of patients with MDD are related to longitudinal course: persisters exhibited a more densely connected network at baseline than remitters. More pronounced associations between symptoms may be an important determinant of persistence in MDD.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the Netherlands2Department.
authors.forename: Claudia
authors.initials: C
authors.lastname: van Borkulo
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the Netherlands.
authors.forename: Lynn
authors.initials: L
authors.lastname: Boschloo
authors.affiliation: Department of Psychology, Psychological Methods Group, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Denny
authors.initials: D
authors.lastname: Borsboom
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Psychology, Psychological Methods Group, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Lourens J
authors.initials: LJ
authors.lastname: Waldorp
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Research School of Behavioural and Cognitive Neurosciences, Interdisciplinary Center for Psychopathology and Emotion Regulation, Groningen, the Netherlands.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schoevers
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008960:Models, Psychological; D011446:Prospective Studies; D012074:Remission Induction; D063189:Symptom Assessment