Faculty Bibliography

Background/UNASSIGNED:Exposure to a traumatic event leads to posttraumatic stress disorder (PTSD) in 10-20% of exposed individuals. Predictors of risk are needed to target early interventions to those who are most vulnerable. The objective of the study was to test whether a noninvasive mobile device that measures a physiological biomarker of autonomic nervous system activation could predict future PTSD symptoms. Methods/UNASSIGNED:Skin conductance response (SCR) was collected during a trauma interview in the emergency department within hours of exposure to trauma in 95 individuals. Trajectories of PTSD symptoms over 12 months post-trauma were identified using Latent Growth Mixture Modeling. Results/UNASSIGNED:<0.00001). Conclusions/UNASSIGNED:The current study is the first prospective study of PTSD showing SCR in the immediate aftermath of trauma predicts subsequent development of chronic PTSD. This finding points to an easily obtained, and neurobiologically informative, biomarker in emergency departments that can be disseminated to predict the development of PTSD.

Alterations of the hypothalamic-pituitary-adrenal (HPA) axis such as altered glucocorticoid receptor sensitivity and increased immune reactivity might contribute to the pathogenesis of major depressive disorder (MDD). Exposure to adverse childhood experiences (ACE) precipitates vulnerability to MDD and might be associated with endocrine and immune alterations in the disorder. In order to disentangle the effects of ACE and MDD, we recruited 87 women: n = 23 with MDD and ACE as determined by clinical interview and questionnaires (Structured Clinical Interview for DSM-IV, Early Trauma Inventory, Childhood Trauma Questionnaire), n = 24 with MDD without ACE, n = 21 with ACE but no current or lifetime MDD, and n = 26 healthy women without either MDD or ACE. Glucocorticoid signaling and mitogen-stimulated proliferation were analyzed ex vivo in peripheral blood-derived mononuclear cells. Additionally, mRNA expression of the glucocorticoid and the mineralocorticoid receptor (GR / MR) was assessed. Peripheral GR sensitivity as well as GR and MR expression levels were not significantly different between groups. Women with ACE showed an increased immune response after mitogen stimulation independent of the presence of MDD. Our results provide evidence for a functionally altered ex-vivo immune response in cell cultures from women with a history of ACE. Thus, ACE might contribute to the pathogenesis of MDD through inflammatory pathways.

Atrial natriuretic peptide (ANP) exerts anxiolytic effects in animals and humans. Patients with anxiety, trauma-associated and depressive disorders exhibit lower ANP plasma levels compared to healthy individuals. However, the role of ANP in patients with major depressive disorder (MDD) with and without concomitant adverse childhood experiences (ACE) and in healthy individuals with and without ACE is not clear. We recruited a total of 93 women: 23 women with MDD and ACE, 24 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD, and 24 healthy women without ACE. ANP plasma levels were measured with a radioimmunoassay. The four groups did not differ in demographic and clinical variables. We found a positive correlation between age and plasma levels of ANP (r = .39; p <  .001). After controlling for age, there was no significant main effect of MDD or ACE on ANP plasma levels, but a significant interaction between MDD and ACE such that ACE was associated with reduced basal ANP levels in the absence of MDD. We assume that low plasma ANP might be a consequence of ACE in the absence of current psychopathology. Therefore, future studies are needed to replicate our findings and to characterize the influencing factors of ACE on ANP more comprehensively, for example by including a comprehensive trauma and comorbidity anamnesis as well as cardiovascular state and risk factors.

BACKGROUND:Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are a prominent finding in patients with major depressive disorder (MDD). Inconsistencies regarding a hyper- or hypoactive HPA axis may be explained by the moderating effect of childhood adverse experiences (ACE) which are associated with both HPA axis dysfunction and MDD in adulthood. We aimed to systematically disentangle the effects of ACE and MDD on HPA axis by comparing healthy women with and without childhood adversity and women with MDD with and without ACE. METHODS:The dexamethasone/corticotropin-releasing hormone (DEX/CRH) test was administered in 35 women with MDD and ACE as determined by a clinical interview (SCID, Early Trauma Inventory), 51 women with MDD without ACE, 21 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. RESULTS:There were no group differences in age, smoking, body mass index, and intake of oral contraceptives. Free salivary cortisol responses were not significantly different between the four groups. CONCLUSIONS:This study shows no evidence for a dysregulation of the HPA axis as measured by the DEX/CRH test in depressed women with and without childhood adversity as compared to mentally healthy women with or without early life stress. Our results do not support the assumption of distinct neuroendocrine endophenotypes in MDD with regard to ACE.

Adverse childhood experiences (ACE) enhance the risk for mental disorders, e.g. major depressive disorder (MDD). Increasing evidence suggests an association between ACE and impaired physical health, e.g. metabolic syndrome. The aim of this study was to assess several metabolic risk markers in healthy individuals with and without ACE and depressed patients with and without ACE. We examined glucose and insulin release in the oGTT in 33 women with MDD and ACE, 47 women with MDD without ACE, 21 women with ACE but no current or lifetime MDD and 36 healthy women without either MDD or ACE. Several metabolic markers such as triglycerides, cholesterol, LDL, HDL, HbA1c, BMI and waist to hip ratio were assessed. The four groups did neither differ in insulin release and glucose concentrations in the oGTT nor with respect to other metabolic variables. Depressed patients with and without psychotropic medication did not differ in any outcome variable, but there was a trend towards higher glucose concentrations in the oGTT in patients with current psychotropic medication. In this physically healthy sample neither ACE nor MDD were associated with metabolic risk factors. Thus, metabolic alterations might not directly be linked to ACE and depression.

BACKGROUND:Adverse childhood experiences (ACE) increase the risk to develop major depressive disorder (MDD) and obesity or metabolic syndrome in adulthood. In addition, ACE may be associated with an exaggerated endocrine response to stress, which, in turn, may lead to enhanced food intake resulting in obesity and metabolic problems. METHODS:We systematically examined the stress response and consecutive food intake in 32 women with MDD and ACE as determined by a clinical interview (Early Trauma Inventory), 52 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. All participants underwent a psychosocial stress test (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST) before they were offered a buffet of snacks. Participants were not aware that the primary outcome variable was the amount of consumed kilocalories (kcal). RESULTS:The four groups did not differ in demographic variables. Stress resulted in higher cortisol release and higher blood pressure compared to the control condition. Patients with MDD without ACE had a significantly lower cortisol response to stress compared to controls. Across groups, we found higher kcal intake after stress compared to the control condition. Comparing high and low cortisol responders to stress, higher kcal intake after stress was only seen in those with low cortisol release. CONCLUSIONS:This study provides evidence that blunted rather than enhanced cortisol release to stress might lead to increased food intake, independent from MDD and ACE.