Faculty Bibliography

INTRODUCTION/BACKGROUND:Growing evidence suggests inhibition dysfunctions in borderline personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary-adrenal (HPA) axis functioning have also been found in BPD patients. In healthy individuals, response inhibition has been sensitive to acute stress, and previous research indicates that effects mediated by the HPA axis become particularly apparent when emotional stimuli are processed. This study aimed to explore the influence of acute hydrocortisone administration on response inhibition of emotional stimuli in BPD patients compared to healthy control participants. METHODS:After a single administration of 10mg hydrocortisone or placebo, 32 female BPD patients and 32 healthy female participants performed an adapted emotional go/no-go paradigm to assess response inhibition for emotional face stimuli in a cross-over study. RESULTS:Acute cortisol elevations decreased the reaction times to target stimuli in both BPD patients and healthy controls. Patients and controls did not differ in task performance; however, BPD patients with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction times than patients without PTSD. In contrast, the occurrence of comorbid eating disorder had no significant impact on go/no-go performance. No significant interaction effect between the treatment condition and the emotional valence of the face stimuli was found. CONCLUSIONS:Acute hydrocortisone administration enhances response inhibition of face stimuli in BPD patients and healthy controls, regardless of their emotional valence. Our results agree with the suggestion that moderate cortisol enhancement increases the inhibition of task-irrelevant distracters.

Depressive syndromes represent a common and often characteristic feature in a number of neurological disorders. One prominent example is the development of post-stroke depression, which can be observed in more than one-third of stroke survivors in the aftermath of an ischemic stroke. Thus, post-stroke depression represents one of the most prevalent, disabling, and potentially devastating psychiatric post-stroke complications. On the other hand, depressive syndromes may also be considered as a risk factor for certain neurological disorders, as recently revealed by a meta-analysis of prospective cohort studies, which demonstrated an increased risk for ischemic events in depressed patients. Moreover, depressive syndromes represent common comorbidities in a number of other neurological disorders such as Parkinson's disease, multiple sclerosis, or epilepsy, in which depression has a strong impact on both quality of life and outcome of the primary neurological disorder.

Glucocorticoids (GCs) have repeatedly been shown to impair hippocampus-mediated, declarative memory retrieval and prefrontal cortex-based working memory in healthy subjects. However, recent experimental studies indicated that patients with major depressive disorder (MDD) lack these impairing effects. These missing effects have been suggested to result from dysfunctional brain GC receptors. The purpose of the present study was to investigate whether response inhibition, an executive function relying on the integrity of the prefrontal cortex, would be impaired after cortisol administration in patients with MDD. In a placebo-controlled, double blind crossover study, 50 inpatients with MDD and 54 healthy control participants conducted an emotional go/no-go task consisting of human face stimuli (fearful, happy, and neutral) after receiving a dose of 10 mg hydrocortisone and after placebo. GC administration had an enhancing effect on inhibitory performance in healthy control participants, indicated by faster responses, while no GC effect was revealed for the patients group. Moreover, patients showed an overall worse performance than healthy participants. In conclusion, this study further supports the hypothesis of impaired central glucocorticoid receptor function in MDD patients. Regarding the importance of inhibitory functioning for daily living, further studies are needed to examine the impact of glucocorticoids on response inhibition.

BACKGROUND:Testosterone binds to androgen receptors, which can be found abundantly in the hippocampus. Associations between testosterone levels and visuospatial memory have been reported, albeit with inconsistent results. Previous studies have used point sampling of testosterone levels (blood, saliva) rather than long-term secretion measures. Hair analysis for steroids allows for retrospective ascertainment of cumulative steroid measures over several months. We examined hair testosterone and its association with verbal and visuospatial memory in middle-aged men and women with and without major depression. METHODS:We examined a total of 73 middle-aged individuals (35 depressed patients, and 38 age-, sex- and education-matched healthy subjects). We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured testosterone in the hair by liquid chromatography tandem mass spectrometry. RESULTS:Hair testosterone levels did not differ between patients and controls (mean 1.35pg/mg vs. 1.40pg/mg, SD 0.61 and 0.80, respectively). In men (n=24) but not women (n=49), hair testosterone was associated with visuospatial memory in a multiple regression analysis after controlling for age, education, body mass index, and depression (adjusted R(2)=0.56). CONCLUSIONS:With the new method of testosterone measurement in hair allowing for long-term cumulative ascertainment of testosterone secretion, we extend recent results of a male-specific role for testosterone in visuospatial memory.

OBJECTIVE:Chronic pain and major depression have been associated with alterations of the hypothalamus-pituitary-adrenal axis (HPA) activity. Previous studies suggested that HPA activity is diminished in chronic pain but increased in depression. However, little is known about the effects of experimentally induced acute pain on cortisol secretion in patients with chronic pain and depression. METHODS:On three different occasions (day 1, day 8, day 90), we repeatedly examined 20 patients with chronic low back pain without depression, 22 patients with major depression without pain, and 33 healthy subjects using heat stimuli. Pain intensity was rated by participants using a visual analog scale. Salivary cortisol was assessed prior to 10 blocks of repeated painful heat stimuli, and 45 and 60 minutes afterwards. RESULTS:In repeated measures analyses of covariance adjusting for age, sex, and time of examination, we found a significant effect of group (P < 0.01) and post-hoc tests confirmed that patients with chronic pain had lower cortisol area-under-the-curve values compared with healthy controls and depressed patients at all time points (all P values <0.01). However, cortisol secretion in depressed patients did not differ from controls. CONCLUSIONS:Across groups, experimental heat pain stimuli did not elicit a significant cortisol response. Chronic pain appears to be associated with low cortisol secretion. The mechanisms linking chronic pain with low cortisol deserve further study.

Major depressive disorder (MDD) has been associated with alterations in the noradrenergic system and impaired memory function. In turn, enhanced memory function has been associated with noradrenergic stimulation. In this study, we examined whether noradrenergic stimulation would differentially improve memory function in patients with MDD and healthy controls. In a placebo-controlled crossover study, 20 patients with MDD and 18 age- and sex-matched healthy controls received either placebo or 5 mg of yohimbine, an alpha-2-adrenoceptor antagonist that causes increased noradrenergic activity, orally before memory testing. A word list paradigm was used to test memory consolidation. Furthermore, the autobiographical memory test assessing memory retrieval and a working memory test were administered. Salivary alpha-amylase and blood pressure were measured. Yohimbine improved memory consolidation (word list learning) across groups (main effect of yohimbine: p = 0.05). This effect was more prominent in depressed patients compared with controls (post hoc t-test: MDD p = 0.01, controls p = 0.77). Memory retrieval (autobiographical memory specificity) and working memory were not affected by yohimbine. Across groups, yohimbine administration resulted in an increase in blood pressure and alpha-amylase. In sum, these results further support the hypothesis that noradrenergic stimulation enhances memory consolidation. The mechanism by which yohimbine leads to stronger memory consolidation in depressed patients compared with healthy controls remains to be elucidated.

Although it has been suggested that glaucoma is associated with circadian misalignment, sleep disorder, anxiety, and depression, these comorbid conditions have not received much attention. This study provides evidence for a significantly higher prevalence of depression, trait anxiety, and sleep disturbances in patients with progressed glaucoma, as compared with glaucoma patients with no or minor visual field defects (VFD). Logistic-regression analyses suggest that severe VFD constitute a significant predictor of depression, trait-anxiety, and sleep disturbance. Results indicate the necessity of regular screening and psychochronobiological treatment in glaucoma patients.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both receptors are also expressed in lymphocytes, but their role for 'escape' of the immune system from endocrine control is unknown. Using steroid sensitivity of T cell function as a read-out system, we here investigate a potential role of mineralocorticoid receptor (MR) versus glucocorticoid receptor (GR) regulation in the immune system as a biological mechanism underlying MS-associated major depression. Twelve female MS patients meeting diagnostic criteria for current major depressive disorder (MDD) were compared to twelve carefully matched MS patients without depression. We performed lymphocyte phenotyping by flow cytometry. In addition, steroid sensitivity of T cell proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells from depressed MS patients. Experiments with agonists suggested disturbed MR regulation, but intact GR function. Importantly, there were no differences in lymphocyte composition and frequency of T cell subsets, indicating that the differences in steroid sensitivity are unlikely to be secondary to shifts in the immune compartment. To our knowledge, this study provides first evidence for altered steroid sensitivity of T cells from MS patients with comorbid MDD possibly due to MR dysregulation.

BACKGROUND:Alterations of the hypothalamus-pituitary-adrenal (HPA) axis are hallmarks in major depressive disorder (MDD) and there is some evidence about similar patterns in borderline personality disorder (BPD). This study examines HPA axis abnormalities with respect to clinical characteristics in both BPD (n=24) and MDD patients (n=33) as well as in healthy control participants (n=41). METHOD/METHODS:A 0.5mg dexamethasone suppression test was administered to evaluate basal cortisol release and HPA feedback sensitivity via salivary cortisol. Traumatic experiences in childhood as well as severity of borderline and depressive symptom severity and dissociation were obtained by self-report questionnaires. RESULTS:Compared to the healthy control group, BPD and MDD patients exhibited both enhanced cortisol concentrations before and after the administration of 0.5mg dexamethasone. Higher cortisol levels were positively correlated to a history of childhood trauma, current dissociative symptoms and severity of borderline and depressive symptoms. Regression analyses revealed that some aspects of early trauma were associated with cortisol release before and after dexamethasone, whereas psychopathology did not contribute to the regression model. CONCLUSIONS:HPA dysfunctions appear to be related rather to childhood trauma than to psychopathology in adulthood. Exposure to childhood trauma may contribute to long-lasting alterations in HPA activity and might enhance the risk for the development of later mental disorder.

BACKGROUND:In the present study, we aimed to compare the effect of exogenous cortisol on memory retrieval in posttraumatic stress disorder (PTSD) with the effects in healthy controls. In healthy participants, administration of cortisol impairs declarative memory retrieval. Only a few studies have investigated these effects in PTSD yielding mixed results. METHODS:In a placebo-controlled crossover study, 44 patients with PTSD and 65 healthy controls received either placebo or 10mg of hydrocortisone orally before memory testing. In addition to declarative memory retrieval (word list learning), we also tested autobiographical memory retrieval specificity. RESULTS:In both tasks opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval, while in PTSD patients cortisol had enhancing effects on memory retrieval in both memory domains. CONCLUSIONS:The present results suggest beneficial effects of acute cortisol elevations on hippocampal mediated memory processes in PTSD. Possible neurobiological mechanisms underlying these findings are discussed.