Objectives. Low serum BDNF levels have been found in depressed patients. No study has systematically investigated whether individual symptoms or symptom profiles within a depressed population contribute to low BDNF levels found in depressed subjects. Methods. All 1070 patients with a past 6-month diagnosis of major depressive disorder from the Netherlands Study of Depression and Anxiety (NESDA) were included. Composite International Diagnostic Interview (CIDI) and Inventory of Depressive Symptoms (IDS) items were tested individually in separate multiple regression analyses with serum BDNF level as the dependent and the CIDI or IDS item as independent variable. Subsequently, we compared BDNF levels between patients with seasonal affective disorder (based on the Seasonal Pattern Assessment Questionnaire) and melancholic depression, atypical depression and moderate depression (based on a latent class analysis). All analyses were adjusted for confounders. Results. Only one item was significantly associated with serum BDNF levels, namely the CIDI item "loss of interest" (β = 0.14; P < 0.01). Counterintuitively the presence of this symptom was associated with higher BDNF levels. Other items and the comparison between different types of depression did not reveal significant differences. Conclusions. Decreased serum BDNF levels in depression cannot be attributed to a specific symptom or symptom cluster.