The primary focus of this dissertation was to increase the knowledge about possible biological factors and psychopathological mechanisms (including HPA-axis functioning, one-carbon and fatty-acid metabolism), as well as some gene-environment interactions for the course of recurrent MDD (MDD-R). Studying MDD-R is important because there are indications that it represents a more biological and genetic determined MDD-subtype, which may be specifically linked to recurrence and CVD-risk.