Reduced amygdala-prefrontal coupling in major depression: association with MAOA genotype and illness severity

The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects. In our control group, we observed tight coupling of the amygdala and dorsal prefrontal areas comprising the dorsolateral prefrontal cortex (DLPFC), dorsal parts of the anterior cingulate cortex (dACC), and lateral orbitofrontal cortex. Amygdala-prefrontal connectivity was significantly reduced in depressed patients and carriers of the higher active MAOA risk alleles (MAOA-H). Hence, depressed MAOA-H carriers showed the weakest amygdala-prefrontal coupling of the investigated subgroups. Furthermore, reduced coupling of this circuitry predicted more than 40% variance of clinical variables characterizing a longer and more severe course of disease. We conclude that genetic variation in the MAOA gene may affect the course of major depression by disrupting cortico-limbic connectivity.     

Vasoprotective endothelial effects of a standardized grape product in humans

The pathogenesis of coronary lesion development is a multi-factorial process involving a number of different cell types and covariates, and injury and dysfunction of the vascular endothelium is an important marker and likely participant in the initiation and/or progression of most forms of heart disease. In addition to chronic dysfunction of endothelial responses in patients with established heart disease, there is evidence that 'acute insults' can cause measurable dysfunction in vascular response in humans (drug toxicities, hypoxia, high fat meal). Such repeated acute insults may contribute to disease risk in otherwise healthy individuals or promote disease progression in established patients. Consumption of grape products, especially wine, has been linked to lower cardiovascular risk but the vascular endothelial effects of grape products in healthy normal subjects, in the absence of ethanol, have not been evaluated. We therefore tested the hypotheses that 1) a standardized product derived from fresh grapes (GP, acute and chronic consumption) improves endothelial performance in healthy normal young subjects, and 2) that concomitant grape consumption affects the 'acute endothelial insult' caused by a single standardized high fat meal (HF). Acute consumption of GP equivalent to 1.25 cups of fresh grapes caused significant improvement in brachial artery flow mediated dilation (FMD) within 3 h of consumption, when compared to control consumption of sugar solution (p<0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were observed. When this 'dose' was then consumed twice daily for 3 weeks FMD was further improved and total antioxidant capacity in plasma was slightly increased (p<0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single HF meal (900 cal, 49 g total fat) caused a 50% reduction in FMD response when consumed alone, and this effect coincided with increased blood triglyceride levels within 3 h post-consumption. In contrast the concomitant consumption of GP with the HF meal completely prevented this HF-induced vascular endothelial dysfunction (p<0.05), but had no effect on rising triglycerides. These data demonstrate that a modest intake of fresh grapes can have acute favorable effects on vascular endothelial function in normal healthy subjects, that chronic intake can further improve performance and concomitant intake can blunt the 'acute insult' to endothelium caused by a typical western HF meal. This effect is likely to be related to antioxidant effects at the endothelium, rather than changes in blood lipids. These data support epidemiological data of the health benefits of grapes, and demonstrate that 'favorable' food consumption can apparently reduce some toxicities induced by 'unfavorable' food consumption.     

Age dependency of cerebral P-gp function measured with (<Emphasis Type="Italic">R</Emphasis>)-[<Superscript>11</Superscript>C]verapamil and PET

Purpose  The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier. Methods  Seven young (mean age: 27 ± 4 years) and six elderly (mean age: 69 ± 9 years) healthy volunteers underwent dynamic (R)-[¹¹C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC). Results  SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC. Conclusions  Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age.     

Alarin is a vasoactive peptide

Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the galanin family of peptides. The GALP gene is characterized by extensive differential splicing in a variety of murine tissues. One splice variant excludes exon 3 and results in a frame shift leading to a novel peptide sequence and a stop codon after 49 aa. In this peptide, which we termed alarin, the signal sequence of the GALP precursor peptide and the first 5 aa of the mature GALP are followed by 20 aa without homology to any other murine protein. Alarin mRNA was detected in murine brain, thymus, and skin. In accordance with its vascular localization, the peptide exhibited potent and dose-dependent vasoconstrictor and anti-edema activity in the cutaneous microvasculature, as was also observed with other members of the galanin peptide family. However, in contrast to galanin peptides in general, the physiological effects of alarin do not appear to be mediated via the known galanin receptors. Alarin adds another facet to the surprisingly high-functional redundancy of the galanin family of peptides.     

A randomised, controlled study on the effects of a short-term endurance training programme in patients with major depression

Objective

To evaluate the short‐term effects of exercise in patients with major depression.

Design

Prospective, randomised, controlled study.

Setting

A university hospital.

Patients

A consecutive series of 38 inpatients with a major depression episode undergoing standard clinical antidepressant drug treatment.

Interventions

Patients were randomly assigned to an exercise (walking, n = 20) or placebo (low‐intensity stretching and relaxation exercises, n = 18) group. Training was carried out for 10 days.

Main outcome measurements

Severity of depression assessed with the Bech‐Rafaelsen Melancholy Scale (BRMS) and the Center for Epidemiologic Studies Depression scale (CES‐D).

Results

After 10 days, reduction of depression scores in the exercise group was significantly larger than in the placebo group (BRMS: 36% v 18%; CES‐D: 41% v 21%; p for both  = 0.01); the proportion of patients with a clinical response (reduction in the BRMS scores by more than six points) was also larger for the exercise group (65% v 22%, p<0.01).

Conclusions

Endurance exercise may help to achieve substantial improvement in the mood of selected patients with major depression in a short time.Exercise has been shown to improve mood and to reduce anxiety in healthy people.^1,2 These findings have led to a growing interest in the effects of physical activity in patients with affective disorders. However, although exercise is often used as an additional treatment for depression, scientific evidence about the effects of this intervention is lacking. Although two meta‐analyses suggested that exercise may be as effective as psychotherapy^3,4 and more effective than other behavioural interventions⁴ for treating depression, a meta‐analysis could not determine the effects of exercise on depression because of a lack of good‐quality research on clinical populations.⁵A growing body of evidence shows that regular physical activity results in functional and morphological adaptations in the brain. Exercise increases the expression of growth factors (insulin‐like growth factor‐I, nerve growth factor and brain‐derived neurotrophic factor), which trigger the production of proteins of signal transduction cascades associated with memory processes.^6,7 Indeed, research in animal models has shown that endurance training increases cortical capillary supplies, the number of synaptic connections and the development of new neurones.⁸ These processes may result in a higher efficiency, plasticity and adaptability of the brain.Several randomised controlled trials have shown that physical activity improves the mood of patients with mild to moderate depression after several weeks.^9,10,11 However, experiments in animals indicate that even a single exercise bout generates considerable changes in the brain concentration of neurotransmitters involved in the pathophysiology of depression.¹² We have previously reported that exercise may substantially improve the mood of patients undergoing bone marrow transplantation¹³ or with therapy‐resistant depression¹⁴ in a short time. The results of a trial suggest that even a single exercise bout may improve the mood of patients with clinical depression.¹⁴ Further, two randomised controlled trials showed an association between exercise amount¹⁵ and duration^11,15 and reduction of symptoms in patients with depression. Finally, a recent study provided evidence for exercise as a possible adjuvant treatment for patients with poor response to antidepressant drugs.¹⁶These findings could be of clinical relevance, as about 30% of patients do not respond to conventional pharmacotherapy, and antidepressants require 1–4 weeks before they show any therapeutic effect. The introduction of exercise programmes in the early treatment of depression could help reduce the duration of therapeutic latency. However, there is a lack of information about several critical features of exercise in the treatment of mood disorders. The diversity of potential clinical populations, the multiple therapeutic settings (single or adjuvant treatment, augmentation to improve remission rates or long‐term treatment) and the variety of exercise programmes are factors that may substantially affect treatment response. Therefore, there is a need for information about the possibilities and mechanisms of action of diverse exercise programmes in patients with depression in different settings. In the present study, we evaluated the effect of a short‐time exercise programme as adjuvant treatment on patients with major depression undergoing standard clinical antidepressant drug treatment.     

Intraosseous myelolipoma

Two patients with lesions in the acetabulum and femur, evident on imaging, were found to have normal marrow elements without a histopathological lesion on curettage of the acetabulum and resection of the femur, respectively. Radiographs on the first patient showed a sclerotic benign appearing acetabular lesion reminiscent of a fibro-osseous lesion while MRI showed the entire lesion to contain fat. The histological features were neither of a fibro-osseous lesion nor a lipoma, but only normal to mildly hypercellular marrow elements. The second patient had a long and expansive femoral osteolytic lesion which on biopsy showed cellular marrow. A subsequent stress fracture led to resection and prosthetic replacement. Microscopic findings revealed only cellular hematopoietic marrow with mature red and white cell lines, megakaryocytes, and a few mast cells devoid of trabecular bones. The microscopic features in the first patient raised the possibility of hematopoietic hyperplasia. Neither the radiographic nor MRI features were consistent with that diagnosis. The spectrum of imaging findings and microscopic appearances in both patients best fit the diagnosis of intraosseous myelolipoma. Case 1 was presented at the Members Meeting of the International Skeletal Society held in Vancouver, Canada in 2006.     

Sachkostenerfassung in der Anästhesie

Background and goal

For reimbursement via diagnosis-related groups (DRG), lump compensation-based payment of medical cases in German hospitals requires a case-related measuring and billing of resources that has to be consistent with DRG guidelines. Only through this, can the real costs be compared with the standard costs as calculated by the hospital reimbursment system (InEK) on a case-related basis and the DRG-specific break-even level be identified.

Methods

In the present paper the authors introduce and validate two newly created alternative methods for case-related allocation of material costs in the field of anaesthesia. Method 1 allows online documentation of material costs via pre-defined anaesthesia standards. This full cost method is suitable for hospitals that have implemented an electronic hospital information system in their daily clinical documentation routine. For other hospitals method 2 could be applicable as the case-related allocation of material costs is done retrospectively based on the data collected in an electronic anaesthesia protocol record system (andoc, medlinq).

Results

Method 1 makes it possible to allocate 90.3% of anaesthesia-related material costs to a specific case corresponding to a Pearsson coefficient of 0.77. After iterative improvement through optimisation of modules the documentation quality could be raised to >98% and a Pearsson coefficient of 0.96. Although the expense for implementation and maintenance is considerable, the necessary documentation work for the clinician is low. Method 2 demands no further clinical effort in documentation and implementation and 49.1% of all material costs can be assigned on a case-related basis.

Conclusions

The online documentation of material costs via predefined anaesthesia standards accounts for nearly all material costs in anaesthesia and only a negligible documentation effort is necessary for the clinician. Nevertheless, a complex and time-consuming configuration of standards and a continuous iterative alignment of the modules with the actual processes are required. Due to its process-orientated character, method 1 can also be usedfor workflow optimisation in terms of standard operating procedures (SOPs). Allocation of material costs with data from the electronic anaesthesia record system is a method that can be easily implemented but only a partial case relation is rendered possible.     

Personalbedarfskalkulation in der Anästhesie

Historically, calculation of staffing requirements for anesthesia has developed from index numbers derived from the workplace method to the service performance method (XX time). The DRG revenues result from an average calculation of costs that results from an assumed calculation of staffing requirements based on the service performance method. In contrast to the principle of full cost coverage, a much stronger process orientation is needed under the conditions of the DRG system. When calculating personnel needs this process orientation also requires that it be oriented to the organization by differentiating between theater-related and non-theater-related anesthesiological services. In a second step the services rendered in a specified organization are then assessed for efficiency and if necessary optimized. Just as it applies to the whole clinical center, in departments of anesthesiology DRG revenues should be brought in line with the actual costs.     

Erfolgsfaktoren im deutschen Krankenhausmarkt

The German hospital market is in a state of transition due to the introduction of diagnosis-related groups (DRGs) and a constant change of the reimbursement, demographic, economical and technical framework. To date mainly public hospitals were bought by private hospital chains, but this trend has currently reached university hospitals. During recent months a consolidation within the market of private hospitals took place, while new market players such as foreign hospital chains, US universities and private equity firms emerged on the scene. The target of the privatisation process, however, turns more and more to larger hospitals. Central key values remain the cluster formation and centralisation of key competences such as food supply, purchasing and pharmacy. Within a network of clinics the representation of different care components (basic, regular and maximum care provider) and care levels (low, normal, intermediate and intensive care) remain important elements of efficient hospital management. Today, successful hospital operation is based on the successful competition for patients and even more for qualified staff. In this aspect, university hospitals could play a decisive role, because of their combination of maximum acute care provision and educational mandate. No such network has yet been formed due to the different interests of the owners, however, given the new market situation this alternative concept could become more attractive.