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Original Investigation |

Association of Symptom Network Structure With the Course of Depression

Claudia van Borkulo, MSc1,2; Lynn Boschloo, PhD1; Denny Borsboom, PhD2; Brenda W. J. H. Penninx, PhD3; Lourens J. Waldorp, PhD2; Robert A. Schoevers, MD, PhD1
[+] Author Affiliations
1University 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
2Department of Psychology, Psychological Methods Group, University of Amsterdam, Amsterdam, the Netherlands
3Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands
JAMA Psychiatry. 2015;72(12):. doi:10.1001/jamapsychiatry.2015.2079.
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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.

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Figure 1.
Network Structures of Persisters and Remitters Before and After Controlling for Severity

Network structures of persisters (n = 253) and remitters (n = 262) based on original data, data after matching on Inventory of Depressive Symptomatology (IDS) sum scores (n = 172 for both groups), and data after World Health Organization Disability Assessment Schedule II (WHODAS II) partialing out. Blue connections represent positive associations, whereas red connections represent negative associations. Thicker edges represent stronger associations (positive or negative). agi indicates psychomotor agitation; con, concentration/decision making; dep, depressed mood; ene, fatigue or loss of energy; gui, feeling guilty; hyp, hypersomnia; ins, insomnia; int, loss of interest or pleasure; ret, psychomotor retardation; sui, suicidality; wap, weight/appetite change.

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Figure 2.
Centrality Measures

Four node centrality measures of persisters and remitters: strength, closeness, betweenness, and eigenvector centrality. agi indicates psychomotor agitation; con, concentration/decision making; dep, depressed mood; ene, fatigue or loss of energy; gui, feeling guilty; hyp, hypersomnia; ins, insomnia; int, loss of interest or pleasure; ret, psychomotor retardation; sui, suicidality; wap, weight/appetite change.

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