Faculty Bibliography

BACKGROUND:The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex and is involved in social cognition. We recently found that pharmacological stimulation of the MR enhances emotional empathy but does not affect cognitive empathy. In the current study, we examined whether blockade of the MR impairs empathy in patients with major depressive disorder (MDD) and healthy individuals. METHODS:In a placebo-controlled study, we randomized 28 patients with MDD without psychotropic medication and 43 healthy individuals to either placebo or 300 mg spironolactone, a MR antagonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. RESULTS:In the MET, we found no significant main effect of treatment or main effect of group for cognitive empathy but a highly significant treatment by group interaction (p < 0.01). Patients had higher cognitive empathy scores compared to controls in the placebo condition but not after spironolactone. Furthermore, in the spironolactone condition reduced cognitive empathy was seen in MDD patients but not in controls. Emotional empathy was not affected by MR blockade. In the MASC, no effect of spironolactone could be revealed. CONCLUSION:Depressed patients appear to exhibit greater cognitive empathy compared to healthy individuals. Blockade of MR reduced cognitive empathy in MDD patients to the level of healthy individuals. Future studies should further clarify the impact of MR functioning on different domains of social cognition in psychiatric patients.

A number of studies have reported on dysfunctions in steroid secretion, including altered cortisol and testosterone levels in borderline personality disorder (BDP) patients compared to healthy controls. The present study extends findings from blood and saliva studies to the cumulative measure of hair steroids. We investigated women with BPD (n=18) and age- and education-matched healthy women (n=17). We did not find differences between BPD patients and healthy women (p=0.40) concerning hair cortisol levels but increased hair testosterone levels among BPD patients compared to controls (p=0.03). These results remained when restricting the analyses to unmedicated patients. Our data indicate altered long-term testosterone but not cortisol levels in females with BPD. Future studies should address the possible impact of altered testosterone on medical illness processes including metabolic syndrome in this population.

RATIONALE AND OBJECTIVES:Major depressive disorder (MDD) is associated with an increased risk for cardiovascular disease (CVD). Apart from biological and life style factors, the use of antidepressants and their potentially adverse effects might contribute to the increased CVD risk. Therefore, we compared cardiovascular risk profiles between relatively young depressed patients without CVD with and without antidepressant medication and healthy participants. METHODS:We investigated 44 depressed patients (with antidepressants N = 20 (13 women), mean age 43.2 years; without antidepressants N = 24 (15 women), mean age 40.0) and 41 healthy participants (matched for sex, age, education). As markers of CVD risk, blood pressure, body mass index (BMI), and plasma levels of fasting glucose, cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and high sensitivity C-reactive protein (h-CRP) were measured. RESULTS:We found significant differences between groups for BMI (p < .01), systolic (p = .02) and diastolic blood pressure (p < .01), and glucose (p < .001). Post hoc analyses indicated differences between both patient groups compared to the healthy control group, but not between patients groups. Further controlling for BMI diminished the effect of diagnosis on blood pressure; however, this was not the case for glucose level. There were no between-group differences in cholesterol, LDL, HDL, and h-CRP. CONCLUSIONS:We found a clearly increased CVD risk in this group of rather young depressed patients. Importantly, there was no significant difference in CVD risk between patients with vs. without antidepressants. This suggests that major depression per se and not antidepressant medication is associated with increased CVD risk.

OBJECTIVES/OBJECTIVE:Stress hormones such as cortisol are known to influence a wide range of cognitive functions, including hippocampal based spatial memory. In the brain, cortisol acts via two different receptors: the glucocorticoid (GR) and the mineralocorticoid receptor (MR). As the MR has a high density in the hippocampus, we examined the effects of pharmacological MR stimulation on spatial memory. METHODS:Eighty healthy participants (40 women, 40 men, mean age=23.9years±SD=3.3) completed the virtual Morris Water Maze (vMWM) task to test spatial encoding and spatial memory retrieval after receiving 0.4mg fludrocortisone, a MR agonist, or placebo. RESULTS:There was no effect of MR stimulation on spatial encoding during the vMWM task. However, participants who received fludrocortisone exhibited improved spatial memory retrieval performance. There was neither a main effect of sex nor a sex-by-treatment interaction. CONCLUSION/CONCLUSIONS:In young healthy participants, MR stimulation improved hippocampal based spatial memory retrieval in a virtual Morris Water Maze task. Our study not only confirms the importance of MR function in spatial memory, but suggests beneficial effects of acute MR stimulation on spatial memory retrieval in humans.

Most of the studies focusing on the effect of stress on false memories by using psychosocial and physiological stressors yielded diverse results. In the present study, we systematically tested the effect of exogenous hydrocortisone using a false memory paradigm. In this placebo-controlled study, 37 healthy men and 38 healthy women (mean age 24.59 years) received either 10 mg of hydrocortisone or placebo 75 min before using the false memory, that is, Deese-Roediger-McDermott (DRM), paradigm. We used emotionally charged and neutral DRM-based word lists to look for false recognition rates in comparison to true recognition rates. Overall, we expected an increase in false memory after hydrocortisone compared to placebo. No differences between the cortisol and the placebo group were revealed for false and for true recognition performance. In general, false recognition rates were lower compared to true recognition rates. Furthermore, we found a valence effect (neutral, positive, negative, disgust word stimuli), indicating higher rates of true and false recognition for emotional compared to neutral words. We further found an interaction effect between sex and recognition. Post hoc t tests showed that for true recognition women showed a significantly better memory performance than men, independent of treatment. This study does not support the hypothesis that cortisol decreases the ability to distinguish between old versus novel words in young healthy individuals. However, sex and emotional valence of word stimuli appear to be important moderators. (PsycINFO Database Record

INTRODUCTION:Stress hormones such as cortisol are involved in modulating emotional memory. However, little is known about the influence of cortisol on the formation of intrusive memories after a traumatic event. The aim of this study was to examine whether cortisol levels during encoding and consolidation of an intrusion-inducing trauma film paradigm would influence subsequent intrusion formation. MATERIAL AND METHODS:In an experimental, double-blind, placebo-controlled study a trauma film paradigm was used to induce intrusions in 60 healthy women. Participants received a single dose of either 20 mg hydrocortisone or placebo before watching a trauma film. Salivary cortisol and alpha-amylase as well as blood pressure were measured during the experiment. The consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions resulting from the trauma film were assessed throughout the following seven days. RESULTS:Hydrocortisone administration before the trauma film resulted in increased salivary cortisol levels but did not affect the consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions throughout the following week. CONCLUSIONS:These results indicate that pharmacologically increased cortisol levels during an experimental trauma film paradigm do not influence consecutive intrusive memories. Current data do not support a prominent role of exogenous cortisol on intrusive memories, at least in healthy young women after a relatively mild trauma equivalent.

Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multifactorial and its heritability is estimated to be approximately 35%. In addition, environmental factors, such as sexual, physical or emotional abuse during childhood, are strongly associated with the risk of developing MDD. No established mechanism can explain all aspects of the disease. However, MDD is associated with alterations in regional brain volumes, particularly the hippocampus, and with functional changes in brain circuits, such as the cognitive control network and the affective-salience network. Furthermore, disturbances in the main neurobiological stress-responsive systems, including the hypothalamic-pituitary-adrenal axis and the immune system, occur in MDD. Management primarily comprises psychotherapy and pharmacological treatment. For treatment-resistant patients who have not responded to several augmentation or combination treatment attempts, electroconvulsive therapy is the treatment with the best empirical evidence. In this Primer, we provide an overview of the current evidence of MDD, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment.

BACKGROUND:Primary adrenal insufficiency (AI) requires hormone replacement therapy with fludrocortisone and hydrocortisone stimulating glucocorticoid (GR) and mineralocorticoid receptors (MR). Evidence from animal and human studies shows that MR function is crucial for cognitive function and mood. Regarding patients with AI, very little is known about the role of MR in cognitive function and mood. METHODS:A repeated-measures within-subject design was used to determine whether cognitive function and mood are related to MR occupation in patients with AI. Intraindividually, patients were examined twice, with 1 week between testing days: once with fludrocortisone (high MR occupation) and once without fludrocortisone (low MR occupation). All patients kept their stable regimen of hydrocortisone. The assessment of cognitive function included executive function, attention, and verbal, visuospatial and working memory. Additionally, mood and blood pressure were measured. RESULTS:Verbal memory improved significantly during high MR occupation (after fludrocortisone intake) compared to low MR occupation [without fludrocortisone, t(29) = -2.1, p = 0.046]. There were trend level differences in the Number-Combination test [t(29) = -1.9, p = 0.074] and in the Stroop interference task [t(29) = -1.9, p = 0.068]. No significant differences in visuospatial and working memory were found. Furthermore, the current mood state was better during high MR occupation compared to low MR occupation [t(29) = -2.4, p = 0.023] as was diastolic blood pressure [F(2, 29) = 3.6, p = 0.07]. CONCLUSIONS:Cognitive function and mood in patients with AI depend in part on MR occupation. Because the medium effect size indicates a potential clinical significance, further studies should systematically examine which dosages of fludrocortisone are associated with optimal cognitive function and mood in AI patients.

INTRODUCTION/BACKGROUND:Emotion recognition and empathy are important aspects in the interaction and understanding of other people's behaviors and feelings. The Human environment comprises of stressful situations that impact social interactions on a daily basis. Aim of the study was to examine the effects of the stress hormone cortisol on emotion recognition and empathy. METHODS:In this placebo-controlled study, 40 healthy men and 40 healthy women (mean age 24.5 years) received either 10mg of hydrocortisone or placebo. We used the Multifaceted Empathy Test to measure emotional and cognitive empathy. Furthermore, we examined emotion recognition from facial expressions, which contained two emotions (anger and sadness) and two emotion intensities (40% and 80%). RESULTS:We did not find a main effect for treatment or sex on either empathy or emotion recognition but a sex × emotion interaction on emotion recognition. The main result was a four-way-interaction on emotion recognition including treatment, sex, emotion and task difficulty. At 40% task difficulty, women recognized angry faces better than men in the placebo condition. Furthermore, in the placebo condition, men recognized sadness better than anger. At 80% task difficulty, men and women performed equally well in recognizing sad faces but men performed worse compared to women with regard to angry faces. CONCLUSION/CONCLUSIONS:Apparently, our results did not support the hypothesis that increases in cortisol concentration alone influence empathy and emotion recognition in healthy young individuals. However, sex and task difficulty appear to be important variables in emotion recognition from facial expressions.

BACKGROUND:Many studies have shown disturbed glucocorticoid receptor (GR) in depressed patients. In contrast, only few studies targeted mineralocorticoid receptor (MR) function with inconclusive results. We examined the effects of the MR antagonist spironolactone on cortisol secretion in depressed patients and healthy individuals. METHODS:Forty-eight unmedicated depressed patients (mean age 41.6years) and 45 age- and sex-matched healthy participants (40.7years) received the MR antagonist spironolactone (300mg) or placebo with three days apart in a randomized, double-blind, within-subject cross-over design. We measured salivary cortisol before ingestion of study medication (baseline) as well as +60min, +90min, +120min, +150min and 180min after baseline. RESULTS:Repeated-measures ANOVA for area under the curve (AUCg) cortisol revealed a treatment effect with higher cortisol after spironolactone and a treatment by group interaction. Post-hoc analyses revealed higher cortisol in depressed patients compared to healthy participants in the placebo condition. In the spironolactone condition, the cortisol levels were not significantly different. CONCLUSIONS:Potentially, impaired MR or GR signaling could be responsible for higher cortisol levels in depressed patients in the placebo condition. However, after MR blockade that increased cortisol secretion across groups leading to higher GR occupation, we found no differences between depressed patients and healthy controls. Thus, our results argue for depression-associated alterations in MR signaling rather than disturbed GR-mediated feedback inhibition.