BackgroundA range of depressive symptoms may occur during an episode of major depression (MD). Do these symptoms describe a single disorder liability or different symptom dimensions? This study investigates the structure and clinical relevance of an expanded set of depressive symptoms in a large general population sample. MethodsWe studied 43,431 subjects from the Dutch Lifelines Cohort Study who participated in an online survey assessing the 9 symptom criteria of MD (DSM-IV-TR) and additional depressive symptoms during their worst lifetime episode of depressive symptoms lasting two weeks or more. Exploratory factor analyses were performed on expanded sets of 9, 14, and 24 depressive symptoms. The clinical relevance of the identified symptom dimensions was analyzed in confirmatory factor analyses including ten external validators. ResultsA single dimension adequately accounted for the covariation among the 9 DSM-criteria, but multiple dimensions were needed to describe the 14 and 24 depressive symptoms. Five dimensions described the structure underlying the 24 depressive symptoms. Three cognitive affective symptom dimensions were mainly associated with risk factors for MD. Two somatic dimensions –appetite/weight problems and sleep problems—were mainly associated with BMI and age, respectively. LimitationsRespondents of our online survey tended to be more often female, older, and more highly educated than non-respondents. ConclusionsDifferent symptom dimensions described the structure of depressive symptoms during a lifetime worst episode in a general population sample. These symptom dimensions resembled those reported in a large clinical sample of Han-Chinese women with recurrent MD, suggesting robustness of the syndrome of MD.