Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study.

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

In vivo magnetic resonance spectrometry imaging demonstrates comparable adaptation of brain energy metabolism to metabolic stress induced by 72 h of fasting in depressed patients and healthy volunteers.

Major depressive disorder (MDD) is characterized by dysregulation of stress systems and by abnormalities in cerebral energy metabolism. Stress induction has been shown to impact neurometabolism in healthy individuals. Contrarily, neurometabolic changes in response to stress are insufficiently investigated in MDD patients. Metabolic stress was induced in MDD patients (MDD, N = 24) and in healthy individuals (CTRL, N = 22) by application of an established fasting protocol in which calorie intake was omitted for 72 h. Both study groups were comparable regarding age, gender distribution, and body mass index (BMI). Fasting-induced effects on brain high-energy phosphate levels and membrane phospholipid metabolism were assessed using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Two-way repeated measures ANOVAs did not reveal significant interaction effects (group x fasting) or group differences in adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), phosphodiesters (PDE), or pH levels between MDD and CTRL. Fasting, independent of group, significantly increased ATP and decreased Pi levels and an overall increase in PME/PDE ratio as marker for membrane turnover was observed. Overall these results indicate reactive changes in cerebral energetics and in membrane phospholipid metabolism in response to fasting. The observed effects did not significantly differ between CTRL and MDD, indicating that neurometabolic adaptation to metabolic stress is preserved in MDD patients.

Epicardial adipose tissue and adrenal gland volume in patients with borderline personality disorder.

Borderline personality disorder (BPD) is associated with an elevated mortality risk that is partially attributed to suicide, but few studies examined other possible causes of premature death. The present study compared epicardial adipose tissue (EAT) volume as a known early predictor of premature cardiovascular morbidity, cardiovascular risk indices, and adrenal gland volume (AGV) as an indicator for chronic hypothalamus-pituitary-adrenal (HPA) axis activation in females with borderline personality disorder (BPD), major depressive disorder (MDD) and in healthy individuals. Twenty-eight patients with BPD comorbid with MDD (BPD/MDD), 22 MDD patients and 26 healthy females (CTRL) of comparable age were included. EAT and AGV were assessed by magnetic resonance tomography; 10-year cardiovascular risk and diabetes risk were determined by PROCAM and FINDRISK score; metabolic syndrome was defined following National Cholesterol Education Adult Treatment Panel III R (NCEP/ATP III) criteria. MADRS was used to assess depression severity. After adjustment for age, body mass index (BMI), and physical activity, EAT and AGV were significantly increased in BPD/MDD compared to MDD and CTRL. EAT and AGV displayed a positive correlation. Finally, diabetes risk in BPD/MDD was elevated compared to CTRL and MDD. The present study highlights the increased cardiometabolic risk of BPD patients. We identify EAT accumulation as an early predictor and potential mediator of cardiovascular disease in BPD that appears to be driven at least in part by HPA axis dysregulation. Therefore, interventions that reduce EAT volume (i.e. exercise and diet) should be considered in the clinical management of BPD.

Increased pericardial adipose tissue and cardiometabolic risk in patients with schizophrenia versus healthy controls.

Patients with schizophrenia are at increased risk of diabetes, cardiovascular disease (CVD) and associated mortality versus the general population. Increased intra-abdominal and pericardial adipose tissue are associated with elevated CVD and mortality in the general population, but little is known about these in patients with schizophrenia. This study examined pericardial and intra-abdominal adipose tissue in schizophrenia and compared this to healthy controls. Thirty-one patients with schizophrenia (mean age 41.2 years, 76% males) and 30 healthy volunteers (CTRL) were examined in this study. The primary outcomes were the volumes of pericardial adipose tissue and intra-abdominal adipose tissue, measured using magnetic resonance imaging. Secondary outcomes included diabetes and cardiac event risk assessed by established instruments. Volumes of pericardial adipose tissue were increased in male and female patients with schizophrenia compared to healthy controls after the adjustment of age, sex and body mass index (P < 0.005). The 10-year risk of a cardiac event was significantly higher in patients with schizophrenia. Furthermore, the risk for developing type-2 diabetes mellitus was slightly increased in schizophrenia. Volumes of intra-abdominal adipose tissue were slightly increased in male and female patients with schizophrenia, albeit not statistically significant. This study demonstrates that patients with schizophrenia have increased pericardial adipose tissue versus controls. This increased fat deposit around the heart is highly relevant for understanding the comorbidity between heart disease and schizophrenia. Interventions aiming to reduce pericardial and intra-abdominal adipose tissue, such as exercise, may be essential to reduce the burden of heart disease in schizophrenia.

Depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from 190 593 people across 43 low- and middle-income countries.

BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs). METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity. RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57). CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.

Exercise increases serum brain-derived neurotrophic factor in patients with major depressive disorder.

BACKGROUND: Brain derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depressive disorder (MDD). Existing data on exercise treatment in people with MDD are inconsistent concerning the effect of exercise on BDNF pointing either to increased or unaltered BDNF concentrations. However, studies in non-depressed persons demonstrated a significant effect on resting peripheral BDNF concentrations in aerobic training interventions. Given the lack of clarity mentioned above, the current study aimed at examining the effect of adjunctive exercise on serum BDNF levels in guideline based treated patients with MDD. METHODS: 42 depressed inpatients were included, and randomized either to a 6 week structured and supervised exercise intervention plus treatment as usual (EXERCISE, n=22), or to treatment as usual (TAU, n=20). BDNF serum concentrations were assessed before and after the intervention in both study groups with established immunoassays. RESULTS: Serum BDNF slightly decreased in the TAU group, whilst there was an increase in BDNF levels in the exercise group. There was a significant time x group effect concerning sBDNF (p=0.030) with repeated ANOVA measures with age and BMI as covariates, suggesting an increase in BDNF concentrations in the EXERCISE group compared to TAU. LIMITATIONS: Though there was no statistic difference in the antidepressant medication between EXERCISE and TAU potential interactions between exercise and medication on the effects of exercise in BDNF cannot be excluded. Gender was not considered as a covariate in ANOVA due to the small number of objects. CONCLUSIONS: Exercise training given as adjunct to standard guideline based treatment appears to have additional effects on BDNF serum concentrations in people with MDD. Our results add further evidence to the beneficial effects of exercise in the treatment of MDD.

[Development and Implementation of a Comprehensive Health Management System (Fit for Work and Life) for Employees of a University Hospital - A Practice Report]. / Entwicklung und Implementierung eines umfassenden Gesundheitsmanagements (Fit for Work and Life) für Mitarbeiter/innen eines Universitätsklinikums ­ ein Praxisbericht.

Background: Due to the increase of sick leave, prolonging working life and the prediction of shortage of skilled workers in the future, health management systems are continuously gaining importance. Employees in a University Hospital are exposed to particular stress factors, which are also reflected in a higher than average amount of sick leave. Against this background, the project "Fit for Work and Life" (FWL) was developed and implemented by the Hannover Medical School (MHH). Aims: FWL aims to maintain, improve or recover the work ability of employees by offering both preventive and rehabilitative treatments. A second goal is to significantly reduce the days of sick leave. Methods: The project was jointly developed and implemented by five MHH departments and the DRV Braunschweig-Hannover (DRV BS-H) according to previously defined principles. It was scientifically evaluated by the following outcomes: average days of sick leave, work ability (WAI), quality of life (SF-36, WHOQOL), coping strategies (FERUS) and effort-reward imbalance (ERI). Results and Conclusions: So far, this project is unique in its concept. It has been successfully implemented in the organisational structures of the MHH. 376 employees have registered during the first project year. Up to now, 182 participants have completed their individual programmes. The results show that 60.4% of employees have moderate to poor WAI values. The average of the mental summary scale of the SF-36 was 44.9, indicating a high workload.

Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

OBJECTIVE: Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). METHODS: The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). RESULTS: PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. CONCLUSION: Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in depressed patients, in particular in chronic depression.

Effects of additional exercise training on epicardial, intra-abdominal and subcutaneous adipose tissue in major depressive disorder: A randomized pilot study.

OBJECTIVE: Major depressive disorder (MDD) is associated with increased amounts of intra-abdominal and epicardial adipose tissue, risk factors for the development of cardio-metabolic disorders. Exercise has been shown to reduce intra-abdominal fat in different conditions such as obesity and diabetes mellitus, thereby reducing cardio-metabolic risks. Therefore we examined the effects of exercise on adipose tissue compartments in patients with MDD. METHODS: Of thirty depressed patients included, twenty received supervised exercise training, and ten received no specific training. Volumes of subcutaneous, intra-abdominal and epicardial adipose tissue were measured using magnetic resonance imaging, and factors constituting the metabolic syndrome were determined. RESULTS: Significant effects of the training condition were observed on the amount of epicardial adipose tissue (P=0.017), subcutaneous adipose tissue (P=0.023), weight (P=0.047), body-mass index (P=0.04), high density lipoproteins (P=0.021) and the number of metabolic syndrome factors (P=0.018). The amount of intra-abdominal adipose tissue decreased slightly, although not significantly, in the exercise group. CONCLUSION: Exercise training reduces the amount of visceral, in particular epicardial adipose tissue, in patients with MDD, and ameliorates factors constituting the metabolic syndrome. Given the high prevalence of cardio-metabolic disorders in major depression, exercise training may be recommended as an additional treatment component.

Antidepressant Treatment with Venlafaxine and Mirtazapine: no Effect on Serum Concentration of Vascular Endothelial Growth Factor (VEGF).

INTRODUCTION: Depression, stress and antidepressant treatment have been found to modulate the expression of growth factors. METHODS: We studied depressed patients receiving randomized treatment with venlafaxine or mirtazapine for 28 days. RESULTS: There was no significant difference between baseline VEGF concentrations in depressed patients compared to healthy controls. We found no significant effect of antidepressant treatment on serum VEGF. DISCUSSION: In contrast to serum BDNF, VEGF may not be a suitable biomarker for effects of antidepressant treatment with venlafaxine or mirtazapine.

Pericardial, intra-abdominal, and subcutaneous adipose tissue in patients with major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD) is associated with an increased risk for developing coronary artery disease (CAD). Recently, pericardial adipose tissue, a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of CAD. Therefore, we investigated pericardial adipose tissue volumes in patients with MDD and compared them to healthy comparison subjects. METHOD: In this case-control study at a university medical center, 50 male and female in-patients with MDD and 25 healthy men and women were examined. The main outcome measures were the volumes of pericardial adipose tissue, intra-abdominal adipose tissue (IaAT) and subcutaneous adipose tissue (ScAT) which were measured using magnetic resonance imaging. RESULTS: The pericardial adipose tissue volumes were greater in men and women with MDD compared with the healthy comparison group following adjustments for the effects of age, weight, height, and physical activity. CONCLUSION: This study expands our knowledge about the alterations in body composition that occur in patients with MDD. The findings are highly relevant for understanding the comorbidity between heart disease and depressive disorders.

[Hypersalivation - inauguration of the S2k Guideline (AWMF) in short form]. / Hypersalivation - Ersterstellung der S2k-Leitlinie (AWMF) in gekürzter Darstellung.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This reduces social interaction chances and burdens daily care. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, and saliva aspiration. Therefore, a multidisciplinary S2k guideline was developed. Diagnostic tools such as fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing studies generate important data on therapy selection and control. Especially traumatic and oncologic cases profit from swallowing therapy programmes in order to activate compensation mechanisms. In children with hypotonic oral muscles, oralstimulation plates can induce a relevant symptom release because of the improved lip closure. In acute hypersalivation, the pharmacologic treatment with glycopyrrolate and scopolamine in various applications is useful but its value in long-term usage critical. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Surgical treatment should be reserved for isolated cases. External radiation is judged as ultima ratio. Therapy effects and symptom severity has to be followed, especially in neurodegenerative cases. The resulting xerostomia should be critically evaluated by the responsible physician regarding oral and dental hygiene.

Assessment of cardiovascular disease risk in patients with schizophrenia spectrum disorders in German psychiatric hospitals: results of the pharmacoepidemiologic CATS study.

PURPOSE: Patients with severe mental illness are at high risk for metabolic and cardiac disorders. Thus, monitoring of cardiovascular risks is imperative and schedules for screening for lipids, glucose, body mass index (BMI), waist-hip ratio and blood pressure have been developed. We intended to analyze screening for metabolic disorders in German patients with schizophrenia spectrum disorders in routine psychiatric care. METHODS: We included 674 patients with any F2 diagnosis in out- and inpatient settings and analyzed metabolic screening procedures as practiced under conditions of usual care. RESULTS: Except BMI (54 %), all other values were documented only in a minority of patients: waist circumference (23 %), cholesterol (28 %), fasting glucose (19 %), triglycerides (25 %) and blood pressure (37 %). We found evidence for less than perfect quality of blood pressure measures. The group of patients who met the individual metabolic syndrome ATP III criteria was comparable to the US CATIE trial. CONCLUSIONS: We conclude that frequency and quality of metabolic monitoring in German in- and outpatients settings are not in accordance with the respective recommendations. Similar to previous reports we found evidence for a high prevalence of metabolic disturbances in German patients with schizophrenia spectrum disorders.

[Psychopharmacotherapy in patients with cardiovascular diseases]. / Psychopharmakotherapie bei Herz-Kreislauf-Erkrankungen.

Increased cardiometabolic morbidity and increased overall mortality has been observed in patients with severe mental disorders. Therefore, cardiometabolic safety is an important issue in the treatment of patients with psychiatric disorders, in particular in patients with comorbid cardiometabolic diseases. Frequent adverse side effects include disturbances of lipid and glucose metabolism, body weight changes and alterations of the QTc interval. Dependent on the particular substance used and on factors concerning individual vulnerability, these side effects vary in relative frequency. Therefore, regular monitoring is recommended including ECG. Furthermore, interactions between different medicaments may occur, either leading to enhanced or decreased drug concentrations. Prior to psychopharmacological treatment, proper cardiological treatment is recommended. The management of cardiovascular risks under psychopharmacology requires interdisciplinary cooperation between the cardiologist, general practitioner and psychiatrist.

[Training in iterative hypothesis testing as part of psychiatric education. A randomized study]. / Training in iterativer Hypothesenbildung in der psychiatrischen Lehre. Eine randomisierte Studie.

BACKGROUND: The improvement of medical education is at the center of efforts to reform the studies of medicine. Furthermore, an excellent teaching program for students is a quality feature of medical universities. Besides teaching of disease-specific contents, the acquisition of interpersonal and decision-making skills is important. However, the cognitive style of senior physicians leading to a diagnosis cannot easily be taught. Therefore, the following study aimed at examining whether specific training in iterative hypothesis testing (IHT) may improve the correctness of the diagnostic process. MATERIALS AND METHODS: Seventy-one medical students in their 9th-11th terms were randomized to medical teaching as usual or to IHT training for 4 weeks. The intervention group received specific training according to the method of IHT. All students were examined by a multiple choice (MC) exam and additionally by simulated patients (SP). The SPs were instructed to represent either a patient with depression and comorbid anxiety and substance use disorder (SP1) or to represent a patient with depression, obsessive-compulsive disorder and acute suicidal tendencies (SP2). RESULTS: All students identified the diagnosis of major depression in the SPs, but IHT-trained students recognized more diagnostic criteria. Furthermore, IHT-trained students recognized acute suicide tendencies in SP2 more often and identified more comorbid psychiatric disorders. The results of the MC exam were comparable in both groups. An analysis of the satisfaction with the different training programs revealed that the IHT training received a better appraisal. CONCLUSIONS: Our results point to the role of IHT in teaching diagnostic skills. However, the results of the MC exam were not influenced by IHT training. Furthermore, our results show that students are in need of training in practical clinical skills.

[The third wave of cognitive-behavioural psychotherapies: concepts and efficacy]. / Die Dritte Welle der Verhaltenstherapie.

During the last two decades a number of psychotherapies have been developed which are summarised as the third wave of cognitive behavioural therapies. Among these are dialectical behaviour therapy (DBT), acceptance and commitment therapy (ACT), schema therapy, cognitive behavioural analysis system of psychotherapy (CBASP), mindfulness-based cognitive therapy (MBCT), and metacognitive therapy (MCT). The purpose of this article is to describe the basic concepts of these treatments and to summarise available studies concerning their efficacy.

Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC).

People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension and dyslipidaemia. Antipsychotic medication and possibly other psychotropic medication like antidepressants can induce weight gain or worsen other metabolic cardiovascular risk factors. Patients may have limited access to general healthcare with less opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. The European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC) published this statement with the aim of improving the care of patients suffering from severe mental illness. The intention is to initiate cooperation and shared care between the different healthcare professionals and to increase the awareness of psychiatrists and primary care physicians caring for patients with severe mental illness to screen and treat cardiovascular risk factors and diabetes.

[Therapeutic options for weight management in schizophrenic patients treated with atypical antipsychotics]. / Möglichkeiten des Gewichtsmanagements in der Behandlung schizophrener Psychosen mit atypischen Antipsychotika.

Extensive, selective literature review of 2500 articles from the last years (up to December 2007) predominantly from Medline and Cochrane, using as search terms "antipsychotic or schizophrenia or individual drug names (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone)" and the terms "BMI, weight gain, metabolic syndrome, diabetes, lipid(s), cholesterol, triglycerides" was conducted. Regardless of the advantages ascribed to atypical antipsychotics and the special effectiveness of clozapine in patients resistant to therapy and at risk for suicide, the probability of weight gain is considerably increased for some of these substances. Patients with schizophrenia have a considerably reduced life expectancy associated with an increased prevalence of cardiovascular risk factors. There is a lack of practical guidelines integrated into clinical psychiatric care for the management of cardiovascular risk factors. The monitoring of patients treated with atypics, which has been recommended in the APA/ADA Consensus Paper in light of these facts, is insufficiently established in clinical practice. A regular monitoring can convey self control and motivation to the patient. In the case of corresponding risk constellations further decisions regarding indication and therapy have to be considered. Especially patients with a high cardiovascular risk profile are highly recommended to participate in a weight-management program for prevention purposes. Such a special program should include elements of dietetic treatment and behaviour and exercise therapy. First controlled studies suggest an effective prevention of weight gain and metabolic changes when applying such a structured program. The practice oriented step by step concept presented here is meant to provide points of reference for the implementation of required medical and psychoeducative measures facilitating the management of weight and further cardiovascular risk factors in the context of psychiatric care in patients with schizophrenia.