GARP inhibits allergic airway inflammation in a humanized mouse model

Background Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. Methods To analyze the therapeutic effects of sGARP, adult NOD/Scidγc−/− (NSG) mice received peripheral blood mononuclear cells (PBMC) …

Dopamine in amygdala gates limbic processing of aversive stimuli in humans

Dopamine is known to contribute to the amygdala-mediated aversive response, where increased dopamine release can augment amygdala function. Combining fMRI and PET imaging techniques, Kienast et al. present findings that suggest a functional link between anxiety temperament, dopamine storage capacity and emotional processing in the amygdala. Dopamine is released under stress and modulates processing of aversive stimuli. We found that dopamine storage capacity in human amygdala, measured with 6-[18F]fluoro-L-DOPA positron emission tomography, was positively correlated with functional magnetic resonance imaging blood oxygen level–dependent signal changes in amygdala and dorsal anterior cingula…

Elevated [18F]FDOPA utilization in the periaqueductal gray and medial nucleus accumbens of patients with early Parkinson's disease

Udgivelsesdato: 2010-Feb-15 PET studies with the DOPA decarboxylase substrate 6-[(18)F]fluoro-l-DOPA (FDOPA) reveal the storage of [(18)F]-fluorodopamine within synaptic vesicles, mainly of dopamine fibres. As such, FDOPA PET is a sensitive indicator of the integrity of the nigrostriatal dopamine innervation. Nonetheless, there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods. To investigate this phenomenon further, we used voxel-wise steady-state kinetic analysis to search for regions of elevated FDOPA utilization (K; ml g(-1) min(-1)) and steady-state trapping (V(d); ml g(-1)) in a …

Childhood methylphenidate treatment of ADHD and response to affective stimuli

Neural correlates of emotional dysregulation in attention-deficit/hyperactivity disorder (ADHD) and persisting influence of Methylphenidate (MPH) still remain insufficiently understood. Decreased activation in the subgenual cingulate and the ventral striatum were found during the perception of positive and negative affective pictures in drug-naïve males with ADHD during childhood (n=10). Males with ADHD during childhood treated with MPH (n=10) did not show any significant differences compared to healthy controls (n=10). Further prospective studies need to clarify direct and indirect mechanisms of MPH treatment that may contribute to emotional processing, which is dysfunctional in males with…

No association of alcohol dependence with a NMDA-receptor 2B gene variant

Mast cell-derived tumour necrosis factor is essential for allergic airway disease

Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear. In order to define the role of mast cells in acute allergic airway disease two strains of mast cell-deficient mice (Kit W/Wv and Kit W-sh/W-sh ) were studied. Compared with their wild-type littermates, Kit W/Wv and Kit W-sh/W-sh mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) fro…

Cross-national time trends in adolescent body weight perception and the explanatory role of overweight/obesity prevalence

Introduction Body weight perception (BWP) is associated with health behaviors. Current evidence points to an increase over time in both actual and perceived weight status among adolescents, however there is limited evidence on time trends in BWP in cross-national samples of adolescents. Therefore, the aims of this study were to examine time trends in BWP between 2002 and 2018 among adolescents from 41 countries and regions, including gender and country differences and to explore the role of changes over time in country-level overweight/obesity prevalence in these trends. Methods Data were used from five cycles (2002, 2006, 2010, 2014, 2018) of the repeated cross-sectional Health Behavior in…

Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in ventral striatum

Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such 'hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent pati…

Asymmetry in dopamine D2/3 receptors of caudate nucleus is lost with age

Molecular and functional imaging techniques reveal evidence for lateralization of human cerebral function. Based on animal data, we hypothesized that asymmetry in dopamine neurotransmission declines during normal aging. In order to test this hypothesis, we measured dopamine D2/3 receptor availability with [18F]desmethoxyfallypride-PET (DMFP) in putamen and caudate nucleus (NC) of 21 healthy, right-handed males (24-60 years; 35+/-10). For volumetric analysis, high-resolution T1-weighted MR-images were obtained in 18 of the PET-subjects in order to assess possible age-related decreases in NC and putamen volume. The calculated DMFP binding potentials (BP) showed a right-ward asymmetry in NC of…

Item response theory and differential test functioning analysis of the HBSC-Symptom-Checklist across 46 countries

Abstract Background The Symptom Checklist (SCL) developed by the Health Behaviour in School-aged Children (HBSC) study is a non-clinical measure of psychosomatic complaints (e.g., headache and feeling low) that has been used in numerous studies. Several studies have investigated the psychometric characteristics of this scale; however, some psychometric properties remain unclear, among them especially a) dimensionality, b) adequacy of the Graded Response Model (GRM), and c) measurement invariance across countries. Methods Data from 229,906 adolescents aged 11, 13 and 15 from 46 countries that participated in the 2018 HBSC survey were analyzed. Adolescents were selected using representative s…

Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli.

Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[ 18 F]fluoro-L-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (K app in ; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes …

Additional file 1 of Item response theory and differential test functioning analysis of the HBSC-Symptom-Checklist across 46 countries

Additional file 1: Table A1. Sample size,percent females, mean, and standard deviation of age. Table A2. Distribution of the HBSC-SCL items (1-4). Table A3. Distribution of the HBSC-SCLitems (5-8). Table A4. Goodness offit statistics for the bifactor GRM. Table A5. Bifactor statistical indices. Table A6. Multigroup Model Fit. Table A7.Monte Carlo simulation results: Mean parameter stability. Figure A1. HBSC-SCL bar charts. Figure A2. HBSC-SCL polychoric correlations. Figure A3. Test for local dependency of the unidimensional GRM. Figure A4. Item fit statistics of theunidimensional GRM. Figure A5. Residualplots of the unidimensional GRM for ALB. FigureA6. Residual plots of the unidimensional…

An integrated genome research network for studying the genetics of alcohol addiction

Alcohol drinking is highly prevalent in many cultures and contributes to the global burden of disease. In fact, it was shown that alcohol constitutes 3.2% of all worldwide deaths in the year 2006 and is linked to more than 60 diseases, including cancers, cardiovascular diseases, liver cirrhosis, neuropsychiatric disorders, injuries and foetal alcohol syndrome. Alcoholism, which has been proven to have a high genetic load, is one potentially fatal consequence of chronic heavy alcohol consumption, and may be regarded as one of the most prevalent neuropsychiatric diseases afflicting our society today. The aim of the integrated genome research network 'Genetics of Alcohol Addiction'-which is a …

Ventral striatal prediction error signaling is associated with dopamine synthesis capacity and fluid intelligence.

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with 1) functional magnetic resonance imaging during a reversal learning task and 2) in a subsample of 17 subjects also with positron emission tomography using 6-[18F]fluoro-L-DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine…

Age-dependent decline of steady state dopamine storage capacity of human brain: an FDOPA PET study.

Conventional indices of the utilization of FDOPA in living human brain have not consistently revealed important declines in dopamine function with normal aging. However, most methods of kinetic analysis have assumed irreversible trapping of decarboxylated FDOPA metabolites in brain, an assumption that is violated even in PET recordings of short duration. Therefore, we have developed methods for the calculation of steady-state storage of FDOPA together with its decarboxylated metabolites (V(d), mlg(-1)), based upon improved kinetic analysis of 120-min emission recordings. In a group of 28 normal male subjects, of age ranging from 23 to 73 years, the magnitude of V(d) in the striatum and in e…

Escitalopram for the prevention of peginterferon-alpha2a-associated depression in hepatitis C virus-infected patients without previous psychiatric disease: a randomized trial

BACKGROUND: Depression is a major complication during treatment of chronic hepatitis C virus (HCV) infection with interferon-alpha (IFN-alpha). It is unclear whether antidepressants can prevent IFN-induced depression in patients without psychiatric risk factors. OBJECTIVE: To examine whether preemptive antidepressant treatment with escitalopram can decrease the incidence or severity of depression associated with pegylated IFN-alpha in HCV-infected patients without a history of psychiatric disorders. DESIGN: Randomized, multicenter, double-blind, prospective, placebo-controlled, parallel-group trial. (ClinicalTrials.gov registration number: NCT00136318) SETTING: 10 university and 11 academic…

Dopamine-modulated aversive emotion processing fails in alcohol-dependent patients.

Negative mood states after alco- hol detoxifi cation may enhance the relapse risk. As recently shown in healthy volunteers, dopamine storage capacity ( V d ) in the left amy- gdala was positively correlated with functional activation in the left amygdala and anterior cin- gulate cortex (ACC) during an emotional task; high functional connectivity between the amy- gdala and the ACC, a region important for emo- tion regulation, was associated with low trait anxiety. Based on these fi ndings, we now tested whether detoxifi ed alcohol-dependent patients have a disrupted modulation of the anterior cin- gulate cortex activation in response to aversive stimuli by amygdala dopamine. Furthermore, we …