Faculty Bibliography

Some people develop symptoms of posttraumatic stress disorder (PTSD) after having experienced a traumatic event, whereas others do not. Intrusive memories are a cardinal symptom of PTSD and a better understanding of encoding and consolidation of intrusive memory may yield important insights on differences in the response to trauma. The primary aim of this study is to investigate whether psychosocial stress induction (Trier Social Stress Test) versus active control (placebo version) leading to respective biological stress responses during the encoding and consolidation of a film-elicited analogue trauma influences the development of intrusive memories over the course of 7 consecutive days. We hypothesized that the activation of the biological stress system increases the number of intrusive memories over the course of 7 days. This single-blind randomized placebo-controlled study examined 122 young healthy women. Biological stress response was measured by salivary cortisol, salivary α-amylase activity, and heart rate variability. Generalized linear mixed models were used to analyze longitudinal effects of activation of biological stress response on self-reported number of intrusive memories. Cross-validated regularized regression (least absolute shrinkage and selection operator) was applied for data-driven feature selection including known biological and psychological predictors. Corroborating our hypothesis, biological stress-responders to the Trier Social Stress Test reported significantly more intrusive memories after trauma film. A priori designed post hoc tests point at significantly more intrusions on Day 1 and 2 in biological stress responders. Least absolute shrinkage and selection operator regression revealed salivary cortisol, salivary α-amylase activity, heart rate variability, subjectively rated distress, fear, and (on trend level) dissociation during the trauma film as relevant predictors of intrusive memories. A heightened biological stress response in young women is associated with more intrusive memories the first days after experiencing a trauma analogue. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The influence of stress on executive functions has been demonstrated in numerous studies and is potentially mediated by the stress-induced cortisol release. Yet, the impact of cortisol on cognitive flexibility and task switching in particular remains equivocal. In this study, we investigated the influence of pharmacological glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) stimulation, two corticosteroid receptor types known to be responsible for cortisol effects on the brain. We conducted two experiments, each with 80 healthy participants (40 women and 40 men), and tested the effect of the unspecific MR/GR agonist hydrocortisone (Experiment I) and the more specific MR agonist fludrocortisone (Experiment II) on switch costs and task rule congruency in a bivalent, cued task switching paradigm. The results did not confirm our hypotheses; we found no significant effects of our manipulations on task switching capacity, although general switching and congruency effects were observed. We discuss the absence of MR/GR-mediated effects and propose alternative mechanisms that could explain stress induced effects on task switching.

The capacity to represent the emotional and mental states of others is referred to by the concept of empathy. Empathy further differentiates into an emotional and a cognitive subcomponent, which in turn is known to require a tacit perspective-taking process. However, whether the empathizer by himself needs to enter an affective state as a necessary precondition for emotional empathy remains a matter of debate. If empathy would require a vicarious emotional reaction, specific physiological markers of affective responding should be detectable in the empathizing person. In the present study, we investigated the relationship between self-reported empathy and psychophysiological responses in young, healthy participants. We assessed emotional and cognitive empathy with the Multifaceted Empathy Test on the one hand and the corresponding heart rate and skin conductance responses (SCR), affective startle modulation and heart rate variability on the other. We found a negative relationship between SCR and self-reported emotional empathy: higher SCR to emotional stimuli predicted lower empathy ratings. We conclude that physiological arousal is not necessary and might even diminish empathy for others.

Endocannabinoids are involved in depressive and anxious symptoms and might play a role in stress-associated psychiatric disorders. While alterations in the endogenous cannabinoid system have been repeatedly found in patients with posttraumatic stress disorder (PTSD), this system has been mostly neglected in borderline personality disorder (BPD). However, there is first evidence for elevated serum levels of the endocannabinoids arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol (2-AG) in BPD patients compared to healthy controls and PTSD patients. In this study, hair endocannabinoids were analyzed, reflecting long-term endocannabinoid concentrations. We assessed AEA concentrations as well as 2-AG and the 2-AG main isomer 1-AG (1-AG/2-AG) in hair in women with BPD (n = 15) and age- and education-matched healthy women (n = 16). We found significantly reduced log AEA in BPD patients compared to healthy women (p = .03) but no differences in log 1-AG/2-AG concentrations. In addition, there was no association between 1-AG/2-AG and hair cortisol, but we found a non-significant correlation between hair concentrations of AEA and cortisol (p = .06). Our data indicate altered long-term release of endogenous cannabinoids in women with BPD depending on type of endocannabinoid. AEA has been suggested to modulate the basal activity of the endocannabinoid system and seems to attenuate depressive and anxious symptoms. Thus, chronically reduced AEA might contribute to psychiatric symptoms in BPD.

Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11β-hydroxysteroid dehydrogenase type 1; 11β -HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1β, or TNF-α. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes.

Cognitive function is often impaired in patients with major depressive disorder (MDD). Childhood trauma is a risk factor for developing MDD and is also associated with cognitive impairments in later life. We aimed to investigate the effects of childhood trauma on cognitive function in MDD. 68 medication-free MDD patients and 75 healthy controls (HC) participated. We tested cognitive function with the Autobiographical Memory Test, Auditory Verbal Learning Test (AVLT), Trail Making Test A and B, Rey-Osterrieth/Taylor Complex Figure Test, and Digit Span Backward. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). Patients and HC did not differ with respect to age, sex, education. Mean CTQ sum scores differed significantly for depressed and HC with mean 47.8 (19.2) and 31.0 (6.8), respectively. Depressed patients and HC (without taking childhood trauma into account) differed only in AVLT performance. When childhood trauma was considered, this group difference disappeared. Subsequent regression analyses revealed that higher CTQ scores but not a diagnosis of MDD were associated with less specific autobiographical memories. Associations of CTQ with other cognitive domains failed significance after correction for multiple testing. Our results suggest that cognitive function is influenced by childhood trauma in MDD. However, the effects are small.

OBJECTIVES:Sex differences have been found in spatial learning and spatial memory, with several studies indicating that males outperform females. We tested in the virtual Morris Water Maze (vMWM) task, whether sex differences in spatial cognitive processes are attributable to differences in spatial learning or spatial memory retrieval in a large student sample. METHODS:We tested 90 healthy students (45 women and 45 men) with a mean age of 23.5 years (SD=3.5). Spatial learning and spatial memory retrieval were measured by using the vMWM task, during which participants had to search a virtual pool for a hidden platform, facilitated by visual cues surrounding the pool. Several learning trials assessed spatial learning, while a separate probe trial assessed spatial memory retrieval. RESULTS:We found a significant sex effect during spatial learning, with males showing shorter latency and shorter path length, as compared to females (all p<0.001). Yet, there was no significant sex effect in spatial memory retrieval (p=0.615). Furthermore, post-hoc analyses revealed significant sex differences in spatial search strategies (p<0.05), but no difference in the number of platform crossings (p=0.375). CONCLUSION:Our results indicate that in healthy young adults, males show faster spatial learning in a virtual environment, as compared to females. Interestingly, we found no significant sex differences during spatial memory retrieval. Our study raises the question, whether men and women use different learning strategies, which nevertheless result in equal performances of spatial memory retrieval.

INTRODUCTION:Traumatic events are often followed by memory impairments of key features of the trauma. Stress hormones are involved in emotional memory formation. However, little is known about their influence during trauma on subsequent recognition memory. MATERIAL AND METHODS:A pooled analysis of two double-blind, placebo-controlled studies (N = 175) was performed to assess the influence of the noradrenergic system and the hypothalamus-pituitaryadrenal (HPA) axis on intrusion formation. Participants received either 10 mg yohimbine (stimulating noradrenergic activity), 0.15 mg clonidine (inhibiting noradrenergic activity), or placebo (noradrenergic manipulation study) or 20 mg hydrocortisone or placebo (hydrocortisone manipulation study), each 60 min before watching a distressing film depicting severe sexual and physical violence. After seven days, the participants performed a 24-item forced choice recognition test. Memory was assessed for pre-, peri-, and post-trauma film scenes. RESULTS:A significant film scene by intervention interaction indicated a differential influence of drug intervention on the number of correct pre-, peri-, and post-trauma film scene memories one week after the distressing film. Post hoc tests revealed that clonidine led to significantly fewer correct peri-trauma film scene memories compared to placebo and, on a trend level, to yohimbine. DISCUSSION:Pharmacological inhibition of noradrenaline during a distressing film leads to impaired emotional recognition memory for the peri-trauma film scene.

Background: Major depressive disorder (MDD) is a complex psychiatric condition with different subtypes and etiologies. Exposure to adverse childhood experiences (ACE) is an important risk factor for the development of MDD later in life. Evidence suggests that pro-inflammatory processes may convey this risk as both MDD and ACE have been related to increased levels of inflammation. In the present study, we aimed to disentangle the effects of MDD and ACE on inflammation levels. Methods: Markers of inflammation (plasma interleukin(IL)-6 and high sensitive C-reactive protein (hsCRP) concentrations, white blood cell (WBC) count and a composite inflammation score (CIS) combining all three) were assessed in 23 MDD patients with ACE, 23 MDD patients without ACE, 21 healthy participants with ACE, and 21 healthy participants without ACE (mean age: 35 ± 11 (SD) years). None of the patients and participants was taking psychotropic medication. ACE was assessed with the Early Trauma Inventory (ETI) and was defined as moderate to severe exposure to sexual or physical abuse. Results: Group differences in the different inflammatory measures were observed. MDD patients with ACE showed significantly higher IL-6 concentrations (p = 0.018), higher WBC counts (p = 0.003) and increased general inflammation levels as indicated by the CIS (p = 0.003) compared to healthy controls. In contrast, MDD patients without ACE displayed similar inflammation levels to the control group (p = 0.93). Conclusion: We observed elevated inflammation in MDD patients with a history of ACE, which could indicate a subtype of "inflammatory depression". Accordingly, MDD patients with ACE might potentially benefit from anti-inflammatory therapies.

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.