News Article | February 15, 2017
-- Largest imaging study of ADHD to date identifies differences in five regions of the brain, with greatest differences seen in children rather than adults. Attention-deficit hyperactivity disorder (ADHD) is associated with the delayed development of five brain regions and should be considered a brain disorder, according to a study published in The Lancet Psychiatry. The study is the largest to look at the brain volumes of people with ADHD, involving more than 3200 people. The authors say the findings could help improve understanding of the disorder, and might be important in challenging beliefs that ADHD is a label for difficult children or the result of poor parenting. ADHD symptoms include inattention and/or hyperactivity and acting impulsively. The disorder affects more than one in 20 (5.3%) under-18 year olds, and two-thirds of those diagnosed continue to experience symptoms as adults. Previous studies have linked differences in brain volume with the disorder, but small sample sizes mean results have been inconclusive. Areas thought to be involved in ADHD are located in the basal ganglia - a part of the brain that controls emotion, voluntary movement and cognition - and research has previously found that the caudate and putamen regions within the ganglia are smaller in people with ADHD. The new international study measured differences in the brain structure of 1713 people with a diagnosis of ADHD and 1529 people without, all aged between four and 63 years old. All 3242 people had an MRI scan to measure their overall brain volume, and the size of seven regions of the brain that were thought to be linked to ADHD - the pallidum, thalamus, caudate nucleus, putamen, nucleus accumbens, amygdala and hippocampus. The researchers also noted whether those with ADHD had ever taken psychostimulant medication, for example Ritalin. The study found that overall brain volume and five of the regional volumes were smaller in people with ADHD - the caudate nucleus, putamen, nucleus accumbens, amygdala and hippocampus. "These differences are very small - in the range of a few percent - so the unprecedented size of our study was crucial to help identify these. Similar differences in brain volume are also seen in other psychiatric disorders, especially major depressive disorder." said lead author Dr Martine Hoogman, Radboud University Medical Center, Nijmegen, The Netherlands.  The differences observed were most prominent in the brains of children with ADHD, but less obvious in adults with the disorder. Based on this, the researchers propose that ADHD is a disorder of the brain, and suggest that delays in the development of several brain regions are characteristic of ADHD. Besides the caudate nucleus and putamen, for which previous studies have already shown links to ADHD, researchers were able to conclusively link the amygdala, nucleus accumbens and hippocampus to ADHD. The researchers hypothesise that the amygdala is associated with ADHD through its role in regulating emotion, and the nucleus accumbens may be associated with the motivation and emotional problems in ADHD via its role in reward processing. The hippocampus' role in the disorder might act through its involvement in motivation and emotion. At the time of their MRI scan, 455 people with ADHD were receiving psychostimulant medication, and looking back further, 637 had had the medication in their lifetime. The different volumes of the five brain regions involved in ADHD were present whether or not people had taken medication, suggesting the differences in brain volumes are not a result of psychostimulants. "The results from our study confirm that people with ADHD have differences in their brain structure and therefore suggest that ADHD is a disorder of the brain," added Dr Hoogman. "We hope that this will help to reduce stigma that ADHD is 'just a label' for difficult children or caused by poor parenting. This is definitely not the case, and we hope that this work will contribute to a better understanding of the disorder."  While the study included large numbers of people of all ages, its design means that it cannot determine how ADHD develops throughout life. Therefore, longitudinal studies tracking people with ADHD from childhood to adulthood to see how the brain differences change over time will be an important next step in the research. Writing in a linked Comment Dr Jonathan Posner, Columbia University, USA, said: "[This] is the largest study of its kind and well powered to detect small effect sizes. Large sample sizes are particularly important in the study of ADHD because of the heterogeneity of the disorder both in the biological cause and clinical manifestation... This study represents an important contribution to the field by providing robust evidence to support the notion of ADHD as a brain disorder with substantial effects on the volumes of subcortical nuclei. Future meta-analyses and mega-analyses will need to investigate medication effects as well as the developmental course of volumetric differences in this disorder." The study was funded by the National Institutes of Health. The study is part of the ENIGMA Consortium, where researchers are also studying the structure of the brain in other psychiatric disorders, allowing researchers to define differences and similarities between the disorders. It was conducted by scientists from Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, University of Southern California, University of Groningen, QIMR Berghofer Medical Research Institute, University Medical Center Utrecht, National Human Genome Research Institute, Asociación para la Innovación en Análisis, Gestión y Procesamiento de Datos Científicos y Tecnológicos, University Hospital Aachen, JARA Translational Brain Medicine, Research Center Juelich, Harvard Medical School, The Broad Institute, University of Bergen, Cincinnati Children's Hospital Medical Center, University of California, UC San Diego, University of Tübingen, University of Würzburg, University of Dublin, NYU Langone Medical Center, King's College London, Heidelberg University, Federal University of Rio de Janeiro, University of Zurich, Child Mind Institute, Nathan Kline Institute for Psychiatric Research, Otto-von-Guericke-University, Maastricht University, University Hospital Frankfurt, Haukeland University Hospital, Child and Adolescent Mental Health Center, Beth Israel Deaconess Medical Center, Karakter Child and Adolescent Psychiatry, VU University Amsterdam, Universitat Autònoma de Barcelona, Fundació IMIM, Hospital Universitari Vall d'Hebron, SUNY Upstate Medical University, National Institute of Mental Health.  Quote direct from author and cannot be found in the text of the Article. IF YOU WISH TO PROVIDE A LINK FOR YOUR READERS, PLEASE USE THE FOLLOWING, WHICH WILL GO LIVE AT THE TIME THE EMBARGO LIFTS: http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(17)30049-4/fulltext
Albrecht M.,University of Kiel |
Meybohm P.,University Hospital Frankfurt |
Broch O.,University of Kiel |
Zitta K.,University of Kiel |
And 5 more authors.
Resuscitation | Year: 2015
Background: Remote ischaemic post-conditioning (RIPoC) in which transient episodes of ischaemia (e.g. by inflation and deflation of a blood pressure cuff) are applied after a prolonged ischaemia/reperfusion injury, may have the potential to improve patient outcome and survival following cardiac arrest. In this study we employed a pig model of cardiac arrest and successful cardiopulmonary resuscitation to evaluate the effects of RIPoC on haemodynamics, cardiac tissue damage and neurologic deficit. Materials and methods: A total of 22 pigs were subjected to ventricular fibrillation, cardiopulmonary resuscitation and randomly assigned to Control or RIPoC treatment consisting of 4 cycles of 5. min femoral artery occlusion followed by 5 min of reperfusion starting 10. min after return of spontaneous circulation (ROSC). Post-resuscitation was evaluated by haemodynamics using left ventricular conductance catheters, quantification of cardiac troponin T (cTnT), lactate dehydrogenase (LDH) and creatine kinase (CK). Neurological testing was performed 24 h after return of spontaneous circulation (ROSC). Results: RIPoC resulted in a statistically significant reduction of serum cTnT levels 4 h after ROSC (P≤ 0.01). LDH and CK concentrations were significantly lower in RIPoC treated pigs 24 h after ROSC (P≤ 0.001), suggesting tissue and/or cardioprotective effects of RIPoC. End-systolic pressure volume relationship was significantly increased in RIPoC treated animals 4 h after ROSC (P≤ 0.05). Neurological testing revealed a trend towards an improved outcome in RIPoC treated animals. Conclusions: We propose that RIPoC applied immediately after ROSC reduces serum concentrations of markers for cell damage and improves end-systolic pressure volume relationship 4 h after ROSC. © 2015 Elsevier Ireland Ltd.
PubMed | University Hospital Frankfurt, University Hospital Aachen and University of Kiel
Type: | Journal: Resuscitation | Year: 2015
Remote ischaemic post-conditioning (RIPoC) in which transient episodes of ischaemia (e.g. by inflation and deflation of a blood pressure cuff) are applied after a prolonged ischaemia/reperfusion injury, may have the potential to improve patient outcome and survival following cardiac arrest. In this study we employed a pig model of cardiac arrest and successful cardiopulmonary resuscitation to evaluate the effects of RIPoC on haemodynamics, cardiac tissue damage and neurologic deficit.A total of 22 pigs were subjected to ventricular fibrillation, cardiopulmonary resuscitation and randomly assigned to Control or RIPoC treatment consisting of 4 cycles of 5 min femoral artery occlusion followed by 5 min of reperfusion starting 10min after return of spontaneous circulation (ROSC). Post-resuscitation was evaluated by haemodynamics using left ventricular conductance catheters, quantification of cardiac troponin T (cTnT), lactate dehydrogenase (LDH) and creatine kinase (CK). Neurological testing was performed 24h after return of spontaneous circulation (ROSC).RIPoC resulted in a statistically significant reduction of serum cTnT levels 4h after ROSC (P 0.01). LDH and CK concentrations were significantly lower in RIPoC treated pigs 24h after ROSC (P 0.001), suggesting tissue and/or cardioprotective effects of RIPoC. End-systolic pressure volume relationship was significantly increased in RIPoC treated animals 4h after ROSC (P 0.05). Neurological testing revealed a trend towards an improved outcome in RIPoC treated animals.We propose that RIPoC applied immediately after ROSC reduces serum concentrations of markers for cell damage and improves end-systolic pressure volume relationship 4h after ROSC.
Martin I.V.,University Hospital Aachen |
Martin I.V.,University of Zürich |
Martin I.V.,RWTH Aachen |
Schmitt J.,University of Zürich |
And 6 more authors.
Biological Chemistry | Year: 2010
The nuclear bile acid receptor FXR (farnesoid-X-receptor) has recently been implicated in the pathophysiology of nonalcoholic fatty liver disease because selective FXR-agonists improve glucose and lipid metabolism in rodent models of obesity. However, the regulation of FXR and other relevant nuclear receptors as well as their lipogenic target genes in fatty liver is still not revealed in detail. Livers were harvested from 14-week-old male ob/ob mice and wild-type controls. Serum bile acids were quantified by radioimmunoassay. mRNA and protein expression of transporters and nuclear receptors was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting, whereas DNA binding to the IR-1 element was examined by electrophoretic mobility shift assay. In this study we show: (i) bile acid retention in ob/ob mice, (ii) a resulting FXR upregulation and binding to the IR-1 element in ob/ob animals and (iii) concomitant activation of the fatty acid synthase as a potential lipogenic FXR target gene in vivo. The present study suggests a potential role of hepatic bile acid retention and FXR activation in the induction of lipogenic target genes. Differences between intestinal and hepatic FXR could explain apparent contradictory information regarding its effects on fatty liver disease. © by Walter de Gruyter Berlin New York.
Liu Z.,RWTH Aachen |
Lammers T.,RWTH Aachen |
Ehling J.,RWTH Aachen |
Ehling J.,University Hospital Aachen |
And 4 more authors.
Biomaterials | Year: 2011
Magnetic resonance (MR) and ultrasound (US) imaging are widely used diagnostic modalities for various experimental and clinical applications. In this study, iron oxide nanoparticle-embedded polymeric microbubbles were designed as multi-modal contrast agents for hybrid MR-US imaging. These magnetic nano-in-micro imaging probes were prepared via a one-pot emulsion polymerization to form poly(butyl cyanoacrylate) microbubbles, along with the oil-in-water (O/W) encapsulation of iron oxide nanoparticles in the bubble shell. The nano-in-micro embedding strategy was validated using NMR and electron microscopy. These hybrid imaging agents exhibited strong contrast in US and an increased transversal relaxation rate in MR. Moreover, a significant increase in longitudinal and transversal relaxivities was observed after US-induced bubble destruction, which demonstrated triggerable MR imaging properties. Proof-of-principle in vivo experiments confirmed that these nanoparticle-embedded microbubble composites are suitable contrast agents for both MR and US imaging. In summary, these magnetic nano-in-micro hybrid materials are highly interesting systems for bimodal MR-US imaging, and their enhanced relaxivities upon US-induced destruction recommend them as potential vehicles for MR-guided US-mediated drug and gene delivery. © 2011 Elsevier Ltd.
PubMed | University Hospital Aachen
Type: Journal Article | Journal: Clinical nuclear medicine | Year: 2012
Reconstruction of striatal dopamine transporter (DAT) SPECT is commonly done by filtered back projection (FBP). We investigated if image reconstruction by 3-dimensional ordered-subset expectation maximization (3D-OSEM) with resolution recovery, which has recently become available for clinical routine, provides a relevant improvement.I-FP-CIT SPECT studies of 18 patients with normal to severely decreased DAT binding were reconstructed by FBP, 2D-OSEM (without resolution recovery), and 3D-OSEM, each with 2 different filter settings, yielding 3 data set pairs of relatively low and high resolution and noise: FBP with seventh-order Butterworth filter [cutoff frequency, 0.36 Nyquist (FBPlow) and 0.45 Nyquist (FBPhigh)] and OSEM with 8 iterations and 8 subsets (2D-/3D-OSEMlow) and 6 iterations and 16 subsets (2D-/3D-OSEMhigh), each with 8-mm Gaussian filtering. Mean regional counts, variability of counts (coefficient of variation), and binding potential (BPND) were assessed by volume-of-interest analyses of the caudate nucleus, the putamen, and the occipital cortex (reference region).On visual inspection, both 2D- and 3D-OSEM-reconstructed images showed an optimal delineation of striatal structures, whereas variability (noise) of nonspecific cortical I-FP-CIT uptake was lowest (most homogenous) with FBPlow, slightly higher with 2D-/3D-OSEMlow, and notably higher for the other methods. Volume-of-interest analyses revealed no significant differences of counts in the occipital reference region in comparison to FBPlow (reference method). In caudate nucleus, counts and, consequently, BPND values increased significantly with FBPhigh (mean BPND change, +5.2%), 2D-OSEMlow/high (+3.7%/+6.2%), and, most notably, 3D-OSEMlow/high (+11.1%/+14.0%). In the putamen, this effect was less pronounced for FBPhigh (+1.8%) and 3D-OSEMlow/high (+5.6%/+6.8%) and failed to reach statistical significance for 2D-OSEMlow/high (-0.2%/+0.8%). Regression analyses indicated excellent correlations of BPND between FBPlow and all other methods (R > 0.97), with the highest regression slopes for 3D-OSEM (1.12-1.16) followed by FBPhigh (1.04-1.06) and then 2D-OSEM (1.01-1.04). The order of the variability of counts in the occipital cortex was as follows: FBPlow (12.5%), 2D-OSEMlow (13.9%), 3D-OSEMlow (14.2%), FBPhigh (15.1%), 2D-OSEMhigh (17.0%), and 3D-OSEMhigh (17.6%).Three-dimensional OSEM considerably improves DAT SPECT reconstruction by offering an optimal combination of high-resolution delineation of striatal structures, superior recovery of signal and BPND, and sufficiently homogeneous nonspecific tracer uptake of the reference region.