Depression and inflammation have been suggested to be involved in the atherosclerotic processes, but empirical evidence is mixed. We tested the hypothesis that depressive symptoms are associated with atherosclerosis only when combined with other risk factors, such as inflammation indicated by indoleamine 2,3-dioxygenase (IDO) activation.Participants were 544 women and 442 men (aged 24–39years) who participated in the Young Finns Study medical examinations in 2001 and 2007. At baseline (in 2001), IDO activity (tryptophan and kynurenine ratio) and other biological and behavioral risk factors were assessed and depressive symptoms were determined using a modified 21-item Beck Depression Inventory. Carotid atherosclerosis was measured on the basis of carotid intimamedia thickness (IMT) at baseline and again in 2007.In women, IDO activity moderated the association between depressive symptoms and IMT (p=0.02), so that a longitudinal association between depressive symptoms and IMT was found only in combination with high IDO activity (B=0.21, p=0.009). This association was robust to adjustment for other risk factors except body mass index and lipids which largely removed the association.The results of this study need to be confirmed using larger data sets and studies using clinical cut-off point for depression.These data suggest that depressive symptoms are associated with preclinical y carotid atherosclerosis only if they are linked to inflammation, and that this association is present only in women. Underlying mechanisms are unknown but probably relate to adiposity.