Objective: Life expectancy in patients suffering from affective disorders is considerably diminished. We investigated whether skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, mediates the association between affective disorders and excess mortality. Methods: Included were 81,041 participants of the Lifelines cohort study. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed with the Mini-International Neuropsychiatric Interview. SAF was assessed as mediator in Cox proportional hazards models for all-cause or natural-cause mortality. Results: Mortality was increased in cases with major depression compared to controls (36.4 vs. 22.5 per 100,000 person years). Partial mediation by SAF of the association between affective disorders and mortality was shown (9.0-10.5%, P<.001-.002), although attenuated by cardiometabolic parameters and history of physical illness. For major depressive disorder, partial mediation by 5.5-10.3% was shown (crude model: P<.001; fully adjusted model: P=.03). Limitations: The relatively short duration of follow-up and the relatively young cohort resulted in a lack of power to detect an association between mortality and dysthymia, social phobia and two or more comorbid disorders. Conclusion: Evidence of partial mediation by SAF of the association between affective disorders and all-cause and natural-cause mortality was demonstrated, although attenuated by health factors. For major depression, mediation by SAF was largest and remained significant after adjustment for sociodemographic and health factors, identifying oxidative stress as possible determinant of premature death.

Original languageEnglish
Pages (from-to)1082-1089
Number of pages8
JournalJournal of affective disorders
Publication statusPublished - 1 Mar 2021


  • Advanced glycation end products
  • Anxiety disorders
  • Mood disorders
  • Mortality
  • Oxidative stress

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