Background: Early onset depression (EOD) and late onset depression (LOD) may be different phenomena. In this study, differences between EOD and LOD in symptomatology, psychiatric characteristics and psychosocial/somatic factors were examined. Methods: Baseline data were from 1104 participants with a current major depressive disorder participating in the Netherlands Study of Depression and Anxiety (age range 18-65 years). DSM-IV diagnoses, depressive symptoms and age of onset were assessed with the Composite International Diagnostic Interview. Analyses were performed by using a continuous as well as a dichotomous (cut-off 40 years) age of onset indicator. Results: Differences between EOD and LOD were observed: longer duration of symptoms (p <.001), a personal history of depressive episodes (p <.001), a serious suicide attempt (p <.001), childhood events (p <.001), a family history of depression (p =.03), and high neuroticism (p <.001) were more often present in EOD than in LOD. Also differences in symptomatology were observed: feelings of sadness (p <.001), diminished concentration (p =.02) and suicidal thoughts (p =.001) were significantly less prevalent at a higher age of onset, whereas decreased appetite/weight loss (p =.01) was more prominent at a higher age of onset. Limitations: The age of first depression onset was asked retrospectively and might be biased by selective recall. However, participants can likely recall whether symptoms started earlier or later in life. Conclusions: Despite similarities, our observed differential findings in symptoms, psychiatric characteristics, and psychosocial factors between EOD and LOD further support that EOD is associated with more frequent occurrence of some clinical features of depression. These differential findings are important factors to keep in mind for diagnostics, treatment, and prevention. © 2012 Elsevier B.V. All rights reserved.