Posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) are highly comorbid. Patients with both disorders report the highest likelihood of lifetime suicide attempts and the lowest mental health related quality of life. Given the high likelihood of comorbid PTSD and BPD and the great burden on those affected, mutual biological and behavioural characteristics of both disorders and their causes seem worthwhile investigating. The current dissertation project aims at further describing overlapping and distinct alterations in stress-regulating systems, stress-relevant brain regions and their interplay in patients with PTSD and BPD, to better explain the evolvement of clinical symptoms, such as affect dysregulation and dissociation that characterize both disorders. As a secondary aim, the current project focusses on the role of childhood trauma (CT), as a mutual environmental factor and possible cause of overlapping symptoms and characteristics in PTSD and BPD. Both disorders are associated with exposure to traumatic events. Traumatic events, such as physical and sexual childhood abuse, in the early phase of development especially increase the risk of developing a psychiatric disorder, among them PTSD and BPD. The organism is especially sensitive to environmental influences in the early period of ontogeny, and changes of stress-regulating systems and stress-relevant brain regions occur in response to stressful environments. Therefore, research has focused on stress-regulating systems and stress-relevant brain regions in both disorders. Especially, the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), fronto-limbic networks and the influences of glucocorticoids on memory retrieval and its neural activity have been investigated. Results suggest that some common features in patients with PTSD and BPD may be related to CT, in addition to distinct features that are related to e.g. genetics or single-event trauma. However, there has been little systematic investigation of distinct and overlapping features in PTSD and BPD, or of how CT is related to features that are present in both patient groups. To further characterize distinct and overlapping features in PTSD and BPD, and the role of CT, the following research questions are examined: 1. How do female patients with PTSD differ in their physiological and subjectively perceived stress response to an acute psychosocial stressor, compared with healthy women, and how do these differences relate to CT? 2. How does amygdala and hippocampus resting state functional connectivity (RSFC) differ between female patients with PTSD and BPD and healthy women, in a placebo condition and after hydrocortisone administration, and how does amygdala or hippocampus RSFC in the placebo or hydrocortisone condition relate to CT? 3. How do female patients with PTSD and BPD differ from healthy women in their neural activity during autobiographical memory (AM) retrieval after hydrocortisone administration compared with a placebo condition, and how do these differences relate to CT? To investigate the psychosocial stress response, we used the Trier Social Stress Test, a well-established psychosocial stressor. To examine the effect of hydrocortisone on RSFC and on neural activity during AM retrieval, we used a standardized resting state scan and an autobiographical memory task adapted for functional magnet resonance imaging. The main results of this dissertation are as follows. First, female patients with PTSD are characterized by a blunted cortisol response to a psychosocial stressor compared with healthy women. Measure of cortisol changes over time in response to a psychosocial stressor correlated negatively with severity of CT. We found no evidence for increased SNS reactivity in female patients with PTSD. Secondly, hippocampus dorsomedial prefrontal cortex (dmPFC) RSFC is reduced in female patients with PTSD and BPD. Hippocampus dmPFC RSFC correlated negatively with severity of CT and clinical symptoms. There were no differences between female patients and healthy women in amygdala RSFC. In addition, there was no influence of hydrocortisone on either amygdala or hippocampus RSFC, nor an interaction of hydrocortisone with group. Thirdly, female PTSD and BPD patients and healthy women did not differ in their neural activity during AM retrieval, neither in the placebo condition nor after hydrocortisone administration. Severity of CT correlated with a hydrocortisone induced pattern of neural activity. To conclude, the conducted studies extend findings on the physiological stress response and fronto-limbic network functioning and on the influence of glucocorticoids on memory retrieval and neural activity in patients with PTSD and BPD. Particularly, the revealed association of CT with a blunted cortisol stress response, decreased hippocampus dmPFC RSFC and a hydrocortisone induced neural activity pattern during AM retrieval, suggest an influence of CT on overlapping features in PTSD and BPD. This dissertation project condenses the current findings into a model that describes how CT might induce changes that partially account for overlapping features in PTSD and BPD. The model focusses on glucocorticoid receptor (GR) functioning and its consequences on HPA axis, SNS and fronto-limbic network functioning, and on the influence of glucocorticoids on memory retrieval and its associated neural activity. The current dissertation project yields important new insights into how CT as a common environmental factor in both disorders results in changes in stress-regulating systems and stress-relevant brain regions, and how these explain overlapping symptoms in both disorders.