dc.description.abstract
Intrusive memories are a core symptom of posttraumatic stress disorder (PTSD), a mental
disorder with a high risk for chronic progression, psychological and physical comorbidities and
socio-functional impairments. Despite extensive research, the mechanisms underlying the
development of PTSD following trauma exposure remain insufficiently understood. There is
increasing evidence that neuroendocrine stress systems, such as the hypothalamic-pituitary-
adrenal (HPA) axis and the noradrenergic system, play a role in the formation of intrusive
memories. Beyond that, the oxytocin system, known for its involvement in stress regulation and
social behavior, has emerged as a promising candidate for PTSD prevention research. However,
findings regarding its effects on memory and stress remain inconclusive and appear to depend on
individual and contextual factors. Oxytocin’s effects seem to be closely intertwined with endocrine
stress system activity, suggesting that variations in physiological stress states may shape its
impact. The use of oral contraceptives (OCs), which alter endocrine functioning, is gaining
recognition as a relevant, yet underexplored, factor in both oxytocin-related and PTSD research.
The primary aim of this dissertation is to investigate whether and how exogenous oxytocin
influences the formation of intrusive (involuntary) memories after a trauma paradigm in healthy
women. A secondary aim is to examine the moderating role of neuroendocrine stress markers,
genetic factors, and OC use on oxytocin’s effects. In addition, the dissertation explores oxytocin’s
influence on voluntary trauma-related memory. To address these questions, four experimental
studies using a validated trauma film paradigm in healthy women were conducted. Study I
examined whether the administration of oxytocin after trauma exposure—during the consolidation
phase—affects the development of intrusive memories. Study II investigated the effects of
oxytocin administration before trauma exposure, mainly targeting the memory acquisition phase.
In both studies, potential moderating effects of individual differences in cortisol (as an indicator of
HPA axis activity), salivary alpha-amylase (sAA; as a marker of noradrenergic activity), heart rate
variability (HRV; reflecting autonomic nervous system regulation), and genetic variations on the
oxytocin effect were explored. Study III investigated whether the use of OCs impacts oxytocin’s
effects on the development of intrusive memories and whether OCs independently influence the
development of intrusive memories. Study IV examined whether oxytocin administration before
or after trauma exposure influences voluntary recognition memory for trauma-related content.
The main findings are as follows: Oxytocin did not exert a general dampening effect on
intrusive memories. Rather, its impact was modulated by timing and individual physiological
profiles. While the administration of oxytocin after a trauma paradigm (Study I) did not influence the subsequent development of intrusive memories, the administration of oxytocin before a trauma
paradigm (Study II) increased intrusive memories in the aftermath. This effect was influenced by
baseline cortisol, HRV, and genetic variation, including polygenic risk scores for PTSD and the
single nucleotide polymorphism rs53576 in the oxytocin receptor gene. OC use did not affect the
impact of oxytocin on intrusive memories. However, participants using OCs showed a blunted
decline in intrusive memories after the trauma film compared to naturally cycling women (Study
III). Voluntary recognition memory was unaffected by oxytocin administration, whether given
before or after the trauma film (Study IV).
In conclusion, the trauma film paradigm enabled a controlled investigation of processes that
cannot be studied during real-life trauma exposure. This dissertation provides novel insights into
the role of oxytocin in trauma-related memory formation and underscores the importance of
accounting for neuroendocrine and genetic moderators (i.e., cortisol, HRV and genetic variations)
when examining oxytocin in the context of PTSD. Notably, the findings suggest that oxytocin
administration prior to trauma exposure may be contraindicated, as it was associated with an
increase in intrusive memories, particularly in individuals with certain physiological profiles. In
contrast, no effects were observed for oxytocin administration after trauma exposure; however,
this absence of effect may be attributable to methodological factors, such as timing, dosage, or
the nature of the trauma analogue. By integrating the biological moderators assessed in this
dissertation into existing models of PTSD, the findings offer promising directions for the
development of targeted, individualized prevention strategies. Although not the primary focus of
this dissertation, the results also point to OC use as a biologically relevant variable that may
influence trauma-related memory processes and should therefore be considered in both future
research and clinical practice.
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