Association of Symptom Network Structure With the Course of [corrected] Depression

Claudia van Borkulo, Lynn Boschloo, Denny Borsboom, Brenda W J H Penninx, Lourens J Waldorp, Robert A Schoevers

Research output: Contribution to JournalArticleAcademicpeer-review


IMPORTANCE: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.

Original languageEnglish
Pages (from-to)1219-1226
Number of pages8
JournalJAMA Psychiatry
Issue number12
Publication statusPublished - Dec 2015


  • Adult
  • Depressive Disorder, Major/diagnosis
  • Disease Progression
  • Female
  • Humans
  • Male
  • Models, Psychological
  • Prospective Studies
  • Remission Induction
  • Symptom Assessment


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