Network outcome analysis identifies difficulty initiating sleep as a primary target for prevention of depression: a 6-year prospective study

Tessa F. Blanken, Denny Borsboom, Brenda Wjh Penninx, Eus Jw Van Someren

Research output: Contribution to JournalArticleAcademicpeer-review


STUDY OBJECTIVES: Major depressive disorder (MDD) is the leading cause of disability worldwide. Its high recurrence rate calls for prevention of first-onset MDD. Although meta-analysis suggested insomnia as the strongest modifiable risk factor, previous studies insufficiently addressed that insomnia might also occur as a residual symptom of unassessed prior depression, or as a comorbid complaint secondary to other depression risks. METHODS: In total, 768 participants from the Netherlands Study of Depression and Anxiety who were free from current and lifetime MDD were followed-up for four repeated assessments, spanning 6 years in total. We performed separate Cox proportional hazard analyses to evaluate whether baseline insomnia severity, short-sleep duration, and individual insomnia complaints prospectively predicted first-onset MDD during follow-up. The novel method of network outcome analysis (NOA) allowed us to sort out whether there is any direct predictive value of individual insomnia complaints among several other complaints that are associated with insomnia. RESULTS: Over 6-year follow-up, 141 (18.4%) were diagnosed with first-onset MDD. Insomnia severity but not sleep duration predicted first-onset MDD (HR = 1.11, 95% CI: 1.07-1.15), and this was driven solely by the insomnia complaint difficulty initiating sleep (DIS) (HR = 1.10, 95% CI: 1.04-1.16). NOA likewise identified DIS only to directly predict first-onset MDD, independent of four other associated depression complaints. CONCLUSIONS: We showed prospectively that DIS is a risk factor for first-onset MDD. Among the different other insomnia symptoms, the specific treatment of DIS might be the most sensible target to combat the global burden of depression through prevention.

Original languageEnglish
Issue number5
Publication statusPublished - 12 May 2020


Support was provided by the European Research Council (ERC-ADG-2014-671084-INSOMNIA) and by a VU University Research Fellowship 2016-2017. The infrastructure for the NESDA study ( is funded through the Geestkracht Program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum).

FundersFunder number
Horizon 2020 Framework Programme671084
European Research CouncilERC-ADG-2014-671084-INSOMNIA
Universiteit Leiden
Rijksuniversiteit Groningen
Vrije Universiteit Amsterdam
Leids Universitair Medisch Centrum


    • insomnia
    • major depressive disorder
    • multivariate analysis
    • network outcome analysis
    • prevention


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