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To investigate whether symptoms of depression increase the risk of low back pain (LBP), after adjusting for genetic and environmental influences.Baseline data of 1607 twins from the Murcia Twin Registry (Spain) were collected in 2009 to 2011 and follow-up data in 2013. Twins answered questions on depression-related symptomatology and LBP. Only participants not reporting chronic LBP (pain >6 mo) at baseline were included. The association between symptoms of depression and LBP was investigated using logistic regression analysis including the complete sample. Subsequent matched within-pair case-control analyses were performed with all complete dizygotic twin pairs discordant for LBP, followed by monozygotic twins.In the total sample analysis, symptoms of depression did not significantly increase the risk of chronic LBP (odds ratio [OR]=1.40; 95% confidence interval [CI], 0.96-2.03), LBP care seeking (OR=1.21; 95% CI, 0.81-1.81), or activity-limiting LBP (OR=1.09; 95% CI, 0.69-1.72). State depression (participants’ symptoms at the moment of the interview) was significantly associated with future care seeking (OR=1.06; 95% CI, 1.01-1.12) and activity-limiting LBP (OR=1.07; 95% CI, 1.01-1.14). A significant association was found between trait depression and activity-limiting LBP (OR=1.05; 95% CI, 1.01-1.10), but not for the other LBP outcomes. No significant association was observed in any of the subsequent case-control analyses.The magnitude of the association between depression and LBP seems to be small and may be confounded by genetic and early shared environment influences, although firm conclusions could not be made due to small sample size in the case-control analysis. In addition, the observed association is dependent on the method of assessment used for both conditions.