This assumption of symptom equivalence goes hand in hand with the conceptualization of depression within the framework of reflective latent variable modeling : variation in the latent disorder depression causes variation of the observable symptoms. Depression is viewed as the common cause for diverse symptoms such as insomnia, psychomotor agitation, or loss of interest – which is the reason why symptoms are measured in order to assess depression. Since all symptoms indicate the same latent disease, only the number of symptoms is relevant, not their natures. The notion that different symptoms are diagnostically equivalent justifies the common practice of summing the number of symptoms to reflect depression severity. However, several authors have suggested that there are substantial benefits to analyzing depressive symptoms individually. This is supported by evidence showing that symptoms differ from each other in their associations with demographic variables, personality traits, lifetime comorbidities, and risk factors, and it has been established that specific stressful life events are predictive of distinct MDD symptom profiles. Furthermore, particular gene polymorphisms are associated with specific depressive symptoms, and a recent study of 7,500 twins concluded that the DSM symptomatic criteria for depression do not reflect a single underlying genetic factor. We are aware of only a single previous study that explored concurrent effects of individual depressive symptoms on impairment of psychosocial functioning. In this PB 203580 analysis of a general population sample, six DSM-III symptoms were significantly associated with impairment. The present study extends the previous report in four important aspects: we examine the differential impact of symptoms on impairment in a large and highly representative sample of 3,703 depressed patients; we use the updated DSM-5 criterion symptoms; we investigate subsymptoms instead of compound symptoms ; lastly, we test whether symptoms vary in their impacts across five impairment domains. Overall, individual depressive symptoms have differential effects on impairment, confirming our main hypothesis. Depressed mood, poor concentration, fatigue and loss of interest explained a large proportion of variance in impairment, whereas weight problems, mid-nocturnal insomnia and hypersomnia made few unique contributions to impairment. Subsymptoms within symptom domains had differential effects as well. For instance, psychomotor retardation explained roughly four times as much variance of impairment as psychomotor agitation. These findings highlight not only the importance of considering the nine DSM symptoms individually, but also the importance of considering sub-symptoms within the symptom domains. The three most debilitating symptoms include one affective, one cognitive and one somatic symptom, suggesting the need to monitor all kinds of depressive symptoms instead of focusing on only one domain or factor score. Furthermore, the two DSM MDD core symptoms, depressed mood and interest loss, made high contributions to explaining impairment, ranking 1 and 4 in general RI estimates.