Emergency referrals for syncopes - is an ambulatory treatment safe?

Patients after syncopy arrive frequently in an emergency unit. Two scoring systems have been validated for clinical decision making, use of diagnostic methods and need for hospitalisation. Goal of the study was quality control of ambulatory treatment of syncope patients in a University Emergency Department. 200 consecutive patients with syncope were documented, 109 of whom followed by phone-call during two years. The decision for hospitalisation or ambulatory treatment was up to the treating doctor. Age-distribution was biphasic: female sex mainly below the age 25, from 55 to 75 predominantly men. Etiology of syncope remained unclear for the majority of cases, a few neurologic (n=3) or cardiac (n=5) reasons were found with treatment consequences.

A patient presenting with metabolic acidosis despite severe vomiting—correct diagnosis by use of the physical-chemical approac

We describe the case of a 28-year-old otherwise healthy woman who presents to our emergency department with nausea for 2 days and severe vomiting for 1 day. She has no history of travel, and her medical history is unremarkable. The physical examination shows a soft and nontender abdomen. Laboratory examinations reveal the presence of significant metabolic alkalosis despite the severe vomiting of the patient. Hypochloremic alkalosis would be expected to be present in this patient. We explain how to correctly identify the rare cause of metabolic acidosis present in this patient using the physicochemical approach (Stewarts approach) for the analysis of human acid-base disorders.

The effects of catecholamine depletion on the neural response to fearful faces in remitted depression

Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [15O]H2O positron emission tomography to assess the brain-catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.

The missing link between clinical states and biomarkers in mental disorders

Current diagnostic definitions of psychiatric disorders based on collections of symptoms encompass very heterogeneous populations and are thus likely to yield spurious results when exploring biological correlates of mental disturbances. It has been suggested that large studies of biomarkers across diagnostic entities may yield improved clinical information. Such a view is based on the concept of assessment as a collection of symptoms devoid of any clinical judgment and interpretation. Yet, important advances have been made in recent years in clinimetrics, the science of clinical judgment. The current clinical taxonomy in psychiatry, which emphasizes reliability at the cost of clinical validity, does not include effects of comorbid conditions, timing of phenomena, rate of progression of an illness, responses to previous treatments, and other clinical distinctions that demarcate major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same psychiatric diagnosis. Clinimetrics may provide the missing link between clinical states and biomarkers in psychiatry, building pathophysiological bridges from clinical manifestations to their neurobiological counterparts.

Psychotherapie und Neuroökonomie

Es gibt zunehmend Beispiele, die belegen, dass die Neuroökonomie als Kombination von ökonomischer Entscheidungstheorie und Neurowissenschaften einen wichtigen Beitrag zur Psychotherapie-Forschung leisten kann. Die Berührungspunkte der beiden Disziplinen sind vielfältig: • Neuroökonomie benutzt Verhaltensexperimente, die es erlauben, komplexes menschliches Verhalten zu untersuchen. Psychotherapie verändert komplexes menschliches Verhalten. Zur Verbesserung der Diagnostik und der Evaluation von Therapieergebnissen können einfache neuroökonomische Experimente einen wichtigen Beitrag leisten. Die experimentelle Messung von zeitlichen, sozialen und Unsicherheitspräferenzen ist besonders geeignet, psychische Störungen zu charakterisieren. • Neuroökonomie ist eine Wissenschaft der menschlichen Motivation. Das Verständnis von bewussten und unbewussten Motivationsfaktoren erlaubt es Psychotherapeutinnen, die Komplexität und Tiefe der Probleme ihrer Patientinnen zu erfassen. • Neuroökonomie ist eine Sozialwissenschaft. Beziehungsprobleme gehören zu den häufigsten Klagen von Patientinnen mit psychischen Störungen, soziale Stressoren sind wichtige Ursachen psychischer Störungen und die therapeutische Beziehung ist der wichtigste Wirkfaktor der Psychotherapie. Die neuroökonomische Erforschung des Sozialverhaltens kann deshalb die Psychotherapie auf unterschiedlichen Ebenen inspirieren. • Neuroökonomie ist eine Neurowissenschaft. Psychotherapie-Forschung beschäftigt sich zunehmend mit Neuroplastizität, insbesondere mit den Effekten von Psychotherapie auf die Funktion und die Struktur des Gehirns. Der neuroökonomische Forschungsansatz macht es möglich, komplexe neuronale Funktionsstörungen bei psychischen Krankheiten zu identifizieren und ihre Modifikation durch Psychotherapie sichtbar zu machen. • Neuroökonomie ist eine umfassende Wissenschaft des menschlichen Verhaltens. Moderne Psychotherapie hat den Anspruch, psychische Störungen auf dem Hintergrund eines bio-psycho-soziales Krankheitsmodells zu verstehen und zu behandeln. Die Neuroökonomie kann einen Beitrag leisten, psychotherapeutische Krankheitsmodelle wissenschaftlich zu fundieren. Die ökonomische Entscheidungstheorie ermöglicht es, die Wechselwirkungen und Synergien von psychotherapeutischer Arbeit, somatischen Behandlungen und sozialen Rahmenbedingungen abzuschätzen. Folgende Eigenschaften schränken die Anwendbarkeit von neuroökonomischen Ansätzen in der Psychotherapie-Forschung allerdings ein: • Das Präferenz-Konzept geht von einer stabilen Verhaltensprädisposition aus. Wechsel von Präferenzen und stark situationsabhängiges Verhalten kann nur beschränkt modelliert werden. • In den meisten neuroökonomischen Experimenten wird Geld als allgemein gültiger Anreiz verwendet. Diese Methodik erlaubt es nicht, reizspezifisches Verhalten zu untersuchen. • Die Neuroökonomie abstrahiert soziale Beziehungen, um sie wissenschaftlich fassbar zu machen. Gewisse Beziehungsaspekte wie beispielsweise die Rolle von Gestik und Mimik können mit dieser Methodik nicht untersucht werden. • Die klassische ökonomische Entscheidungstheorie ist besonders geeignet, „kalte“, überlegte Entscheidungen zu verstehen. Impulsives und zeitinkonsistentes Verhalten kann mit dieser Theorie nur ungenügend beschrieben werden. Neuroökonomie ist eine junge Wissenschaft mit grossem Entwicklungspotential. Führende theoretische und Experimentalökonomen sind daran, Theorie und Forschungsmethodik zu erweitern, um situations- und reizspezifische Faktoren besser zu berücksichtigen und das „heisse“ Ende des Spektrums von Entscheidungsfindungen besser zu verstehen.

Metabotropic glutamate receptor 5 binding in patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.

Low dose irinotecan improves advanced lupus nephritis in mice potentially by changing DNA relaxation and anti–double-stranded DNA binding

Objective Albeit clear advances in the treatment of SLE, many patients still present with refractory lupus nephritis requiring new treatment strategies for this disease. Here we determined whether reduced doses of the topoisomerase I inhibitor irinotecan, which is known as chemotherapeutic agent, were able to suppress SLE in NZB/W F1 mice. We further evaluated the potential mechanism how irinotecan influenced the course of SLE. Methods NZB/W F1 mice were treated with low dose irinotecan either from week 24 of age or from established glomerulonephritis defined by a proteinuria ≥grade 3+. Binding of anti-dsDNA antibodies was measured by ELISA; and DNA relaxation was visualized by gel electrophoresis. Results Significantly reduced irinotecan dosages improved lupus nephritis and prolonged survival in NZB/W F1 mice. The lowest dose successfully used for the treatment of established murine lupus nephritis was more than 50 times lower than the dose usually applied for chemotherapy in humans. As a mechanism, low dose irinotecan reduced B cell activity; however, the levels of B cell activity in irinotecan-treated mice were similar to those in Balb/c mice of the same age suggesting that irinotecan did not induce a clear immunosuppression. In addition, incubation of double-stranded (ds) DNA with topoisomerase I increased binding of murine and human anti-dsDNA antibodies showing for the first time that relaxed DNA is more susceptible to anti-dsDNA antibody binding. This effect was reversed by addition of the topoisomerase I inhibitor camptothecin. Conclusion Our results propose topoisomerase I inhibitors as a novel and targeted therapy for SLE. © 2014 American College of Rheumatology.

The role of learning-related dopamine signals in addiction vulnerability

Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction.

Relationship between genome and epigenome - challenges and requirements for future research

Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set the vision for future policies and research agendas at the European level.

Der Spiegel : eine Epistel f. Antisemiten u. Semiten

von Gregor Gog

The Role of BDNF, Leptin and Catecholamines in Reward Learning in Bulimia Nervosa

Background: A relationship between bulimia nervosa (BN) and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Methods: Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted BN (rBN) and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 h after a standardized breakfast. Results: AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (p = 0.05). Across conditions, plasma BDNF levels were higher in rBN subjects compared to controls (diagnosis effect; p = 0.001). Plasma BDNF and leptin levels were higher in the morning before compared to after a standardized breakfast across groups and conditions (time effect; p < 0.0001). The plasma leptin levels were higher under catecholamine depletion compared to placebo in the whole sample (treatment effect; p = 0.0004). Conclusions: This study reports on preliminary findings that suggest a catecholamine-dependent association of plasma BDNF and reward learning in subjects with rBN and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both rBN and controls.