Time after Time: Biological factors in the course of recurrent depression

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 MDDR 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. For this reason we expected these patients to deviate the
strongest from healthy controls in the (patho)physiological and genetic mechanisms and to have
more pronounced alterations in their course of MDD.
We considered two leading hypotheses that potentially could explain the underlying mechanism
for the high risk for recurrence: (I) the vulnerability-accumulation or scarring hypothesis and
(II) the premorbid vulnerability hypothesis. Our aim was to investigate specific premorbid
factors (e.g. genetics, childhood trauma) that are present before MDD onset as well as the specific
biological factors that could play a premorbid role and/or are involved in vulnerabilityaccumulation (‘scarring’). These biological variables were collected in different stadia in the
course of MDD-R, i.e. the remitted phase, subsyndromal phase and acute depressive state.
Studies in this thesis are mostly based on data collected from the participants of the DELTA
study: a well-defined high-risk population for relapse and recurrence as it includes exclusively
remitted patients with at least two previous depressive episodes.