Telomere length in individuals with and without major depression and adverse childhood experiences.

Major depressive disorder (MDD) and adverse childhood experiences (ACE) are associated with poor physical and mental health in adulthood. One underlying mechanism might be accelerated cellular aging. For example, both conditions, MDD and ACE, have been related to a biological marker of cellular aging, accelerated shortening of telomere length (TL). Since MDD and ACE are confounded in many studies, we aimed with the current study to further disentangle the effects of MDD and ACE on TL using a full-factorial design including four carefully diagnosed groups of healthy participants and MDD patients with and without ACE (total N = 90, all without use of antidepressants). As dependent variable, TL was assessed in leukocytes. We found no group differences based on MDD and ACE exposure in TL. While TL was negatively associated with age and male sex, TL was not associated with any measure of severity of MDD, ACE or current stress. One possible explanation for our null result may be the comparatively good physical health status of our sample. Future research is needed to elucidate the relation of TL, MDD and ACE, taking potential effect modification by medication intake and physical health status into account.

Real-world evidence from a European cohort study of patients with treatment resistant depression: Healthcare resource utilization.

BACKGROUND: Treatment resistant depression (TRD) is diagnosed when patients experiencing a major depressive episode fail to respond to ≥2 treatments. Along with substantial indirect costs, patients with TRD have higher healthcare resource utilization (HCRU) than other patients with depression. However, research on the economic impact of this HCRU, and differences according to response to treatment, is lacking. METHODS: This multicenter, observational study documented HCRU among patients with TRD in European clinical practice initiating new antidepressant treatments. Data regarding access to outpatient consultations and other healthcare resources for the first 6 months, collected using a questionnaire, were analyzed qualitatively according to response and remission status. The economic impact of HCRU, estimated using European costing data, was analyzed quantitatively. RESULTS: Among 411 patients, average HCRU was higher in non-responders, attending five times more general practitioner (GP) consultations and spending longer in hospital (1.7 versus 1.1 days) than responders. Greater differences were observed according to remission status, with non-remitters attending seven times more GP consultations and spending approximately three times longer in hospital (1.7 versus 0.6 days) than remitters. Consequently, the estimated economic impacts of non-responders and non-remitters were significantly greater than those of responders and remitters, respectively. LIMITATIONS: Key limitations are small cohort size, absence of control groups and generalizability to different healthcare systems. CONCLUSION: Patients with TRD, particularly those not achieving remission, have considerable HCRU, with associated economic impact. The costs of unmet TRD treatment needs are thus substantial, and treatment success is fundamental to reduce individual needs and societal costs.

Real-world evidence from a European cohort study of patients with treatment resistant depression: Treatment patterns and clinical outcomes.

BACKGROUND: Treatment resistant depression (TRD) characterizes a subgroup of 10-30% of patients with major depressive disorder, and is associated with considerable morbidity and mortality. A consensus treatment for TRD does not exist, which often leads to wide variations in treatment strategies. Real-world studies on treatment patterns and outcomes in TRD patients in Europe are lacking and could help elucidate current treatment strategies and their efficacy. METHODS: This non-interventional cohort study of patients with TRD (defined as treatment failure on ≥2 oral antidepressants given at adequate dose and duration) with moderate to severe depression collected real-world data on treatment patterns and outcomes in several European countries. Patients were started on a new treatment for depression according to routine clinical practice. RESULTS: Among 411 patients enrolled, after 6 months, only 16.7% achieved remission and 73.5% showed no response. At Month 12, while 19.2% achieved remission and 69.2% showed no response, 33.3% of those in remission at Month 6 were no longer in remission. Pharmacological treatments employed were heterogenous; 54 different drugs were recorded at baseline, and the top 5 treatment types according to drug classes accounted for 40.0% of patients. Even though remission rates were very low, at Month 12, 60.0% of patients had not changed treatment since enrolment. CONCLUSIONS: The heterogeneity of treatments highlights a lack of consensus. Moreover, despite low response rates, patients often remained on treatments for substantial periods of time. These data further support existence of an unmet treatment need for TRD patients in Europe.

Real-world evidence from a European cohort study of patients with treatment resistant depression: Baseline patient characteristics.

BACKGROUND: Treatment resistant depression (TRD; failure to respond to ≥2 treatments) affects ~20% of patients with major depressive disorder (MDD). Real-world data could help describe patient characteristics and TRD disease burden, to assess the unmet needs of TRD patients in Europe. METHODS: This observational study collected data from adults with moderate to severe TRD initiating a new treatment for depression, according to local standards of care. At baseline, socio-demographic characteristics, medical history, prior and current treatments were recorded. Disease severity, health-related quality of life (HRQoL), functionality and productivity were assessed. RESULTS: Overall, 411 eligible patients were enrolled across seven European countries. Mean (standard deviation [SD]) patient age was 51.0 (10.8) years; 62.3% were female. Long-term sick leave was reported by 19.0% of patients; 30.2% were unemployed. The mean (SD) duration of the current episode was 2.6 (3.9) years. At baseline, mean (SD) HRQoL scores for EuroQoL 5-dimension 5-level (UK tariff) and EQ-Visual Analog Scale were 0.41 (0.25) and 41.1 (18.7), respectively. The Work Productivity and Activity Impairment questionnaire demonstrated mean (SD) absenteeism of 57.0% (44.9%) and presenteeism of 54.7% (29.5%); mean (SD) overall work impairment was 60.5% (29.9%). LIMITATIONS: Key limitations are small cohort size, absence of a control group and generalizability to countries with different healthcare models. CONCLUSIONS: TRD patients had a high disease burden, low HRQoL and reduced function and productivity, with a substantial proportion unable to work. This demonstrates an unmet treatment need in TRD patients that, if addressed, could reduce the heavy personal and societal burden.

Major depression and atrial natriuretic peptide: The role of adverse childhood experiences.

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.

Psychosocial stress differentially affects emotional empathy in women with borderline personality disorder and healthy controls.

OBJECTIVE: Deficits in empathy, an important part of social cognition, have been described in patients with borderline personality disorder (BPD). Importantly, psychosocial stress enhances emotional empathy in healthy participants. However, it remains unknown whether stress affects empathy in BPD. METHOD: We randomized 47 women with BPD and 47 healthy women to either the Trier Social Stress Test or a control condition. Subsequently, all participants underwent the Multifaceted Empathy Test (MET), a measure of cognitive and emotional facets of empathy. RESULTS: Across groups, stress resulted in a significant increase in cortisol and stress ratings. There was a significant stress × group interaction for emotional empathy (Fdf1,92 = 5.12, P = 0.04, ηp2 = 0.05). While there was no difference between patients with BPD and healthy participants after the control condition, patients with BPD had significantly lower emotional empathy scores after stress compared to healthy individuals. There were no effects for cognitive empathy. CONCLUSION: The current finding provides first evidence that stress differentially affects emotional empathy in patients with BPD and healthy individuals such that patients with BPD showed reduced emotional empathy compared to healthy women after stress. Given the strong impact of stress on acute psychopathology in patients with BPD, such a response may exacerbate interpersonal conflicts in stress contexts and may be an important target for therapeutic interventions.

Influence of the noradrenergic system on the formation of intrusive memories in women: an experimental approach with a trauma film paradigm.

BACKGROUND: Intrusive memories of traumatic events are a core feature of post-traumatic stress disorder but little is known about the neurobiological formation of intrusions. The aim of this study was to determine whether the activity of the noradrenergic system during an intrusion-inducing stressor would influence subsequent intrusive memories. METHOD: We conducted an experimental, double-blind, placebo-controlled study in 118 healthy women. Participants received a single dose of either 10 mg yohimbine, stimulating noradrenergic activity, or 0.15 mg clonidine, inhibiting noradrenergic activity, or placebo. Subsequently, they watched an established trauma film which induced intrusions. The number of consecutive intrusions resulting from the trauma film, the vividness of the intrusions, and the degree of distress evoked by the intrusions were assessed during the following 4 days. Salivary cortisol and α-amylase were collected before and after the trauma film. RESULTS: A significant time × treatment interaction for the number of intrusions and the vividness of intrusions indicated a different time course of intrusions depending on treatment. Post-hoc tests revealed a delayed decrease of intrusions and a delayed decrease of intrusion vividness after the trauma film in the yohimbine group compared with the clonidine and placebo groups. Furthermore, after yohimbine administration, a significant increase in salivary cortisol levels was observed during the trauma film. CONCLUSIONS: Our findings indicate that pharmacological activation of the noradrenergic system during an emotionally negative event makes an impact on consecutive intrusive memories and their vividness in healthy women. The noradrenergic system seems to be involved in the formation of intrusive memories.

Stress and Depression: a Crucial Role of the Mineralocorticoid Receptor.

Cortisol and corticosterone act on the appraisal process, which comprises the selection of an appropriate coping style and the encoding of the experience for storage in the memory. This action exerted by the stress hormones is mediated by mineralocorticoid receptors (MRs), which are expressed abundantly in the limbic circuitry, particularly in the hippocampus. Limbic MR is down-regulated by chronic stress and during depression but induced by antidepressants. Increased MR activity inhibits hypothalamic-pituitary-adrenal axis activity, promotes slow wave sleep, reduces anxiety and switches circuit connectivity to support coping. Cortisol and emotion-cognition are affected by MR gene haplotypes based on rs5522 and rs2070951. Haplotype 1 (GA) moderates the effects of (early) life stressors, reproductive cycle and oral contraceptives. MR haplotype 2 (CA) is a gain of function variant that protects females against depression by association with an optimistic, resilient phenotype. Activation of MR therefore may offer a target for alleviating depression and cognitive dysfunction. Accordingly, the MR agonist fludrocortisone was found to enhance the efficacy of antidepressants and to improve memory and executive functions in young depressed patients. In conclusion, CORT coordinates via MR the networks underlying how an individual copes with stress, and this action is complemented by the widely distributed lower affinity glucocorticoid receptor (GR) involved in the subsequent management of stress adaptation. In this MR:GR regulation, the MR is an important target for promoting resilience.

[Treatment of depression in coronary heart disease]. / Behandlung der Depression bei koronarer Herzerkrankung.

Depression and coronary heart disease (CHD) are leading causes of disability and show a high comorbidity. Furthermore, depression is an independent risk factor for an unfavorable course and increased mortality in patients with CHD. In contrast, successful treatment of depression can reduce the risk of cardiac events. Currently, there are several treatment options for the management of depression in CHD, including self-management strategies, psychotherapy, pharmacotherapy and collaborative care models. This article provides an overview of the epidemiology of depression in CHD, the mechanisms of association and the current state of evidence with respect to the different treatment options.

Antidepressants, autonomic function and mortality in patients with coronary heart disease: data from the Heart and Soul Study.

BACKGROUND: Antidepressants reduce depressive symptoms in patients with coronary heart disease, but they may be associated with increased mortality. This study aimed to examine whether the use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) is associated with mortality in patients with coronary heart disease, and to determine whether this association is mediated by autonomic function. METHOD: A total of 956 patients with coronary heart disease were followed for a mean duration of 7.2 years. Autonomic function was assessed as heart rate variability, and plasma and 24-h urinary norepinephrine. RESULTS: Of 956 patients, 44 (4.6%) used TCA, 89 (9.3%) used SSRI, and 823 (86.1%) did not use antidepressants. At baseline, TCA users exhibited lower heart rate variability and higher norepinephrine levels compared with SSRI users and antidepressant non-users. At the end of the observational period, 52.3% of the TCA users had died compared with 38.2% in the SSRI group and 37.3% in the control group. The adjusted hazard ratio (HR) for TCA use compared with non-use was 1.74 [95% confidence interval (CI) 1.12-2.69, p = 0.01]. Further adjustment for measures of autonomic function reduced the association between TCA use and mortality (HR = 1.27, 95% CI 0.67-2.43, p = 0.47). SSRI use was not associated with mortality (HR = 1.15, 95% CI 0.81-1.64, p = 0.44). CONCLUSIONS: The use of TCA was associated with increased mortality. This association was at least partially mediated by differences in autonomic function. Our findings suggest that TCA should be avoided in patients with coronary heart disease.

Investigating recurrent neural networks for OCT A-scan based tissue analysis.

OBJECTIVES: Optical Coherence Tomography (OCT) has been proposed as a high resolution image modality to guide transbronchial biopsies. In this study we address the question, whether individual A-scans obtained in needle direction can contribute to the identification of pulmonary nodules. METHODS: OCT A-scans from freshly resected human lung tissue specimen were recorded through a customized needle with an embedded optical fiber. Bidirectional Long Short Term Memory networks (BLSTMs) were trained on randomly distributed training and test sets of the acquired A-scans. Patient specific training and different pre-processing steps were evaluated. RESULTS: Classification rates from 67.5% up to 76% were archived for different training scenarios. Sensitivity and specificity were highest for a patient specific training with 0.87 and 0.85. Low pass filtering decreased the accuracy from 73.2% on a reference distribution to 62.2% for higher cutoff frequencies and to 56% for lower cutoff frequencies. CONCLUSION: The results indicate that a grey value based classification is feasible and may provide additional information for diagnosis and navigation. Furthermore, the experiments show patient specific signal properties and indicate that the lower and upper parts of the frequency spectrum contribute to the classification.

Structural analysis of FeO(1 1 1)/Ag(0 0 1): undulation of hexagonal oxide monolayers due to square lattice metal substrates.

Iron oxide monolayers are grown on Ag(0 0 1) via reactive molecular beam epitaxy (metal deposition in oxygen atmosphere). The monolayer shows FeO stoichiometry as concluded from x-ray photoemission spectra. Both low energy electron diffraction as well as scanning tunneling microscopy demonstrate that the FeO layer has a quasi-hexagonal (1 1 1) structure although deposited on a surface with square symmetry. Compared to bulk values, the FeO(1 1 1) monolayer is unidirectionally expanded by 3.4% in [Formula: see text] directions while bulk values are maintained in [Formula: see text] directions. In [Formula: see text] directions, this lattice mismatch between FeO(1 1 1) monolayer and Ag(0 0 1) causes a commensurate undulation of the FeO monolayer where 18 atomic rows of the FeO(1 1 1) monolayer match 17 atomic rows of the Ag(0 0 1) substrate. In [Formula: see text] directions, however, the FeO(1 1 1) monolayer has an incommensurate structure.

Neuronal differences between chronic low back pain and depression regarding long-term habituation to pain.

BACKGROUND: Longitudinal studies of experimental pain are rare and little is known about the differences regarding sensitization and habituation over longer periods in patients with chronic pain or depression compared with controls. METHODS: We used a standardized longitudinal painful heat paradigm that was designed to induce long-term habituation in 19 patients with chronic low back pain (CLBP), 21 patients with depression (DEP) and 21 healthy participants (controls) over a time course of eight consecutive days. We applied functional magnetic resonance imaging on the first and last day of this period and after 3 months. RESULTS: Although the pain paradigm was standardized, patients with DEP exhibited significantly higher pain thresholds and a trend to higher pain ratings and, in functional imaging, showed less activation of the operculum and the secondary somatosensory cortex (S2) as compared to patients with CLBP and controls. Conversely, patients with CLBP showed increased activation in the anterior insula and parietal operculum as compared to patients with DEP and controls. Within session, all participants sensitized to pain, which was associated with higher activation levels in the thalamus, amygdala, midcingulate cortex, and sensory and motor areas. However, patients with depression showed significantly less activation in midbrain and brainstem areas. CONCLUSION: Given that pain and depression potentiate each other clinically, our data suggest that this may involve different cortical pain areas.

Association between cortisol awakening response and memory function in major depression.

BACKGROUND: While impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in each group. METHOD: We examined 21 patients with major depression without medication, 20 depressed patients on antidepressant treatment, and 41 age-, sex- and education-matched healthy subjects. We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured CAR on two consecutive days. RESULTS: Patient groups did not differ in severity of depression. We found a significant effect of group (p = 0.03) for CAR. Unmedicated patients exhibited a greater CAR compared with medicated patients (p = 0.04) with no differences between patient groups and HC. We found a significant effect of group for verbal (p = 0.03) and non-verbal memory (p = 0.04). Unmedicated patients performed worse compared with medicated patients and HC in both memory domains. Medicated patients and HC did not differ. Regression analyses revealed a negative association between CAR and memory function in depressed patients, but not in HC. CONCLUSIONS: While in unmedicated depressed patients the magnitude of CAR is associated with impaired memory, medicated patients showed a smaller CAR and unimpaired cognitive function compared with HC. Our findings are compatible with the idea that antidepressants reduce CAR and partially restore memory function even if depressive psychopathology is still present.

Retrospective comparison of prednisolone and ursodeoxycholic acid for the treatment of feline lymphocytic cholangitis.

A retrospective study was performed to evaluate the effect of treatment with prednisolone or ursodeoxycholic acid (UDCA) on the survival times of 26 cats with lymphocytic cholangitis, and to determine prognostic factors. Most affected cats were males (76.9%, P=0.006) and a breed predisposition for the Norwegian Forest Cat was demonstrated (P=0.021). Clinical signs included weight loss, icterus, anorexia, vomiting, and listlessness. Blood analyses revealed elevated hepatic enzymes, bile acids and hypergammaglobulinaemia. Breed, sex, and therapeutic regimen were significantly associated with survival times. Prednisolone treatment resulted in a statistically longer survival time compared to UDCA.

Effects of cortisol on memory in women with borderline personality disorder: role of co-morbid post-traumatic stress disorder and major depression.

BACKGROUND: Stress and cortisol administration are known to have impairing effects on memory retrieval in healthy humans. These effects are reported to be altered in patients with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) but they have not yet been investigated in borderline personality disorder (BPD). METHOD: In a placebo-controlled cross-over study, 71 women with BPD and 40 healthy controls received either placebo or 10 mg of hydrocortisone orally before undertaking a declarative memory retrieval task (word list learning) and an autobiographical memory test (AMT). A working memory test was also applied. RESULTS: Overall, opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval whereas in BPD patients cortisol had enhancing effects on memory retrieval of words, autobiographical memory and working memory. These effects were most pronounced for specificity of autobiographical memory retrieval. Patients with BPD alone and those with co-morbid PTSD showed this effect. We also found that co-morbid MDD influenced the cortisol effects: in this subgroup (BPD + MDD) the effects of cortisol on memory were absent. CONCLUSIONS: The present results demonstrate beneficial effects of acute cortisol elevations on hippocampal-mediated memory processes in BPD. The absence of these effects in patients with co-morbid MDD suggests that these patients differ from other BPD patients in terms of their sensitivity to glucocorticoids (GCs).

[Depression and neurological diseases]. / Depression und neurologische Erkrankungen.

In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous effect on the course and the prognosis. On the other hand depression is also a risk factor for certain neurological diseases as was recently demonstrated in a meta-analysis of prospective cohort studies which revealed a much higher stroke risk for depressive patients. Furthermore, depression plays an important role in other neurological diseases with respect to the course and quality of life, such as Parkinson's disease, multiple sclerosis and epilepsy. This article gives a review of the most important epidemiological, pathophysiological and therapeutic aspects of depressive disorders as a comorbidity of neurological diseases and as a risk factor for neurological diseases.

[Depression: risk factor for cardiovascular disease]. / Depression: risikofaktor für kardiovaskuläre Erkrankungen.

Major depression is an independent risk factor for the development of cardiovascular disease. In patients with existing cardiovascular disease, major depression has a large impact on the quality of life and is associated with a poor course and prognosis. Potential mechanisms responsible for this association can be categorized as biological and behavioural variables that do not exclude each other but interact. Biological factors include alterations of the autonomous nervous system, the hypothalamic-pituitary-adrenal axis, the immune system and the vascular system. Major depression also raises the risk for further diseases, such as diabetes mellitus or obesity, which themselves are associated with higher cardiovascular risks. On a behavioural level, depression is often associated with an unhealthy life style such as smoking and physical inactivity. Additionally, depressed patients have more difficulties to implement recommended behavioural changes and to adhere to medication. Furthermore, some classes of antidepressants may also increase cardiovascular risk. All these factors play an important role in the association between depression and cardiovascular disease.

Detection of bacterial DNA in bile of cats with lymphocytic cholangitis.

In this study, we have successfully used molecular methods based on the amplification of the 16S ribosomal RNA gene on feline bile samples to show that bile of cats with LC is not sterile. This is probably due to the fact that the inflammatory process in the biliary tree causes dilatations. As a result, bacteria can easily migrate from the intestines via the common bile duct. The diversity of species identified and the presence of Helicobacter spp. DNA in both patients and controls suggests that bacteriobilia is secondary to the disease and is not the cause of LC.

[Cholangitis in cats: symptoms, cause, diagnosis, treatment, and prognosis]. / Cholangitis bij kat symptomen, oorzaak, diagnose, therapie en prognose.

Inflammation of the bile ducts is common in cats. This review article reports on what is currently known about the various types of cholangitis (i.e., cholangitis caused by liver flukes, neutrophilic cholangitis, and lymphocytic cholangitis). Treatment is available for cholangitis caused by liver flukes and for neutrophilic cholangitis, and the prognosis is good. However, the cause of lymphocytic cholangitis is not known and there is currently no evidence-based therapy. Several causes are mentioned in the literature, but more research is needed in order to establish the cause of this disease and to develop an appropriate therapy.