OBJECTIVES: Growth differentiation factor-15 (GDF-15) is an inflammatory molecule that reacts to cell stress. Since major depression is associated with inflammation, we examined whether GDF-15 levels are elevated in patients with late-life depression. METHODS: Plasma GDF-15 levels were analyzed in 350 patients diagnosed with major depressive disorder in the last six months and 128 non-depressed controls from the Netherlands Study of Depression in Older persons (age >/= 60 years). Major depressive disorder and age of onset were assessed with the Composite International Diagnostic Interview. Severity of depressive symptoms was measured with the Inventory of Depressive Symptoms (IDS-30). Multiple linear regression models were applied to study depression (diagnosis, onset age, severity, antidepressant drug use) as determinant of GDF-15 level, adjusted for demographic and clinical variables. RESULTS: Plasma GDF-15 levels were 22% higher in patients with major depression compared to controls. Within the depressed group, levels were higher in patients with older age of onset. GDF-15 levels showed a small, positive correlation to the levels of the inflammatory mediators IL-6 and C-reactive protein (r=0.23, and 0.24, p