No abstract

Mood disorders are associated with regional brain abnormalities, including reductions in glial cell and neuron number, glutamatergic irregularities, and differential patterns of brain activation. Because astrocytes are modulators of neuronal activity and are important in trafficking the excitatory neurotransmitter glutamate, it is possible that these pathologies are interrelated and contribute to some of the behavioral signs that characterize depression and related disorders. We tested this hypothesis by determining whether depressive-like signs were induced by blocking central astrocytic glutamate uptake with the astrocytic glutamate transporter (GLT-1) inhibitor, dihydrokainic acid (DHK), in behavioral tests that quantify aspects of mood, including reward and euthymia/dysthymia: intracranial self-stimulation (ICSS) and place conditioning. We found that DHK elevated ICSS thresholds, a depressive-like effect that could reflect reduced sensitivity to reward (anhedonia) or increased aversion (dysphoria). However, DHK treatment did not establish conditioned place aversions, suggesting that this treatment does not induce dysphoria. To identify the brain regions mediating the behavioral effects of DHK, we examined c-Fos expression in areas implicated in motivation and emotion. DHK increased c-Fos expression in many of these regions. The dentate gyrus of the hippocampus was robustly activated, which led us to explore whether DHK alters hippocampal learning. DHK impaired spatial memory in the MWM. These findings identify disruption of astrocyte glutamate uptake as one component of the complex circuits that mediate anhedonia and cognitive impairment, both of which are common symptoms of depression. These finding may have implications for the etiology of depression and other disorders that share the features of anhedonia and cognitive impairment.

BackgroundGastro-oesophageal reflux disease (GERD) is a common disorder with consequences for the patient's health-related quality of life (HRQoL). In Germany, few data are available on the impact of GERD on work-related productivity.AimTo study the impact of GERD on work productivity despite proton pump inhibitor (PPI) therapy and the association between productivity and symptom duration, severity, and HRQoL.MethodsRetrospective data from randomly selected patients with chronic GERD symptoms, treated by office-based general practitioners or general internists with routine clinical care, were analyzed together with information from self-administered instruments assessing work productivity (WPAI-GERD), symptoms (RDQ), and HRQoL (QOLRAD).ResultsReduced productivity was reported by 152 of 249 patients (61.0%), although 89.5% of them were treated with PPI. The reduction in work productivity was 18.5% in all patients and 30.3% in those with reduced productivity. Patients with impaired productivity showed a significantly lower HRQoL and more-severe symptoms of reflux disease. In all patients, the mean sick leave attributable to reflux symptoms was 0.6 hours in the previous seven days and 1.4 work days in the previous three months.ConclusionGERD has a substantial impact on work productivity in Germany, even in patients receiving routine clinical care and PPI therapy.