TY - JOUR A1 - Heinsen, Helmut A1 - Strik, M. A1 - Luther, K. A1 - Ulmar, G. A1 - Gangnus, D. A1 - Jungkunz, G. A1 - Eisenmenger, W. A1 - Götz, M. A1 - Bauer, M. T1 - Cortical and striatal neurone number in Huntington's disease N2 - The total cortical and striatal neurone and glial numbers were estimated in five cases of Huntington's disease (three males, two females) and five ageand sex-matched control cases. Serial 500-l-lm-thick gallocyanin-stained frontal sections through the left hemisphere were analysed using Cavalieri's principle for volume and the optical disector for cell density estimations. The average cortical neurone number of five controls (mean age 53±13 years, range 36-72 years) was 5.97x 109±320x 106 , the average number of small striatal neurones was 82 X 106± 15.8 X 106• The left striatum (caudatum, putamen, and accumbens) contained a mean of 273 X 106±53 X 106 glial cells (oligodendrocytes, astrocytes and unc1assifiable glial profiles). The mean cortical neurone number in Huntington's disease patients (mean age 49±14 years, range 36-75 years) was diminished by about 33 % to 3.99x109±218x106 nerve cells (P ::;:::: 0.012, MannWhitney V-test). The mean number of small striatal neurones decreased tremendously to 9.72 X 106 ± 3.64 X 106 (-88 % ). The decrease in total glial cells was less pronounced (193 X 106±26 X 106) but the mean glial index, the numerical ratio of glial cells per neurone, increased from 3.35 to 22.59 in Huntington's disease. Qualitatively, neuronal loss was most pronounced in supragranular layers of primary sensory areas (Brodmann's areae 3,1,2; area 17, area 41). Layer HIc pyramidal cells were preferentially lost in association areas of the temporal, frontal, and parietal lobes, whereas spared layer IV granule cells formed a conspicuous band between layer IH and V in these fields. Methodological issues are discussed in context with previous investigations and similarities and differences of laminar and lobar nerve cellloss in Huntington's disease are compared with nerve cell degent-ration in other neuropsychiatric diseases. KW - Medizin KW - Huntington's disease . Human cerebral cortex KW - Striatum KW - Neurone number KW - Stereology Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-55217 ER - TY - JOUR A1 - Manchia, Mirko A1 - Adli, Mazda A1 - Akula, Nirmala A1 - Arda, Raffaella A1 - Aubry, Jean-Michel A1 - Backlund, Lena A1 - Banzato, Claudio E. M. A1 - Baune, Bernhard T. A1 - Bellivier, Frank A1 - Bengesser, Susanne A1 - Biernacka, Joanna M. A1 - Brichant-Petitjean, Clara A1 - Bui, Elise A1 - Calkin, Cynthia V. A1 - Cheng, Andrew Tai Ann A1 - Chillotti, Caterina A1 - Cichon, Sven A1 - Clark, Scott A1 - Czerski, Piotr M. A1 - Dantas, Clarissa A1 - Del Zompo, Maria A1 - DePaulo, J. Raymond A1 - Detera-Wadleigh, Sevilla D. A1 - Etain, Bruno A1 - Falkai, Peter A1 - Frisén, Louise A1 - Frye, Mark A. A1 - Fullerton, Jan A1 - Gard, Sébastien A1 - Garnham, Julie A1 - Goes, Fernando S. A1 - Grof, Paul A1 - Gruber, Oliver A1 - Hashimoto, Ryota A1 - Hauser, Joanna A1 - Heilbronner, Urs A1 - Hoban, Rebecca A1 - Hou, Liping A1 - Jamain, Stéphane A1 - Kahn, Jean-Pierre A1 - Kassem, Layla A1 - Kato, Tadafumi A1 - Kelsoe, John R. A1 - Kittel-Schneider, Sarah A1 - Kliwicki, Sebastian A1 - Kuo, Po-Hsiu A1 - Kusumi, Ichiro A1 - Laje, Gonzalo A1 - Lavebratt, Catharina A1 - Leboyer, Marion A1 - Leckband, Susan G. A1 - López Jaramillo, Carlos A. A1 - Maj, Mario A1 - Malafosse, Alain A1 - Martinsson, Lina A1 - Masui, Takuya A1 - Mitchell, Philip B. A1 - Mondimore, Frank A1 - Monteleone, Palmiero A1 - Nallet, Audrey A1 - Neuner, Maria A1 - Novák, Tomás A1 - O'Donovan, Claire A1 - Ösby, Urban A1 - Ozaki, Norio A1 - Perlis, Roy H. A1 - Pfennig, Andrea A1 - Potash, James B. A1 - Reich-Erkelenz, Daniela A1 - Reif, Andreas A1 - Reininghaus, Eva A1 - Richardson, Sara A1 - Rouleau, Guy A. A1 - Rybakowski, Janusz K. A1 - Schalling, Martin A1 - Schofield, Peter R. A1 - Schubert, Oliver K. A1 - Schweizer, Barbara A1 - Seemüller, Florian A1 - Grigoroiu-Serbanescu, Maria A1 - Severino, Giovanni A1 - Seymour, Lisa R. A1 - Slaney, Claire A1 - Smoller, Jordan W. A1 - Squassina, Alessio A1 - Stamm, Thomas A1 - Steele, Jo A1 - Stopkova, Pavla A1 - Tighe, Sarah K. A1 - Tortorella, Alfonso A1 - Turecki, Gustavo A1 - Wray, Naomi R. A1 - Wright, Adam A1 - Zandi, Peter P. A1 - Zilles, David A1 - Bauer, Michael A1 - Rietschel, Marcella A1 - McMahon, Francis J. A1 - Schulze, Thomas G. A1 - Alda, Martin T1 - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report JF - PLoS ONE N2 - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. KW - age KW - observer agreement KW - prophylactic lithium KW - mapping susceptibility genes KW - mood disorders KW - onset KW - association KW - reliability KW - morality KW - illness Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938 VL - 8 IS - 6 ER - TY - JOUR A1 - Farmer, Adam D. A1 - Strzelczyk, Adam A1 - Finisguerra, Alessandra A1 - Gourine, Alexander V. A1 - Gharabaghi, Alireza A1 - Hasan, Alkomiet A1 - Burger, Andreas M. A1 - Jaramillo, Andrés M. A1 - Mertens, Ann A1 - Majid, Arshad A1 - Verkuil, Bart A1 - Badran, Bashar W. A1 - Ventura-Bort, Carlos A1 - Gaul, Charly A1 - Beste, Christian A1 - Warren, Christopher M. A1 - Quintana, Daniel S. A1 - Hämmerer, Dorothea A1 - Freri, Elena A1 - Frangos, Eleni A1 - Tobaldini, Eleonora A1 - Kaniusas, Eugenijus A1 - Rosenow, Felix A1 - Capone, Fioravante A1 - Panetsos, Fivos A1 - Ackland, Gareth L. A1 - Kaithwas, Gaurav A1 - O'Leary, Georgia H. A1 - Genheimer, Hannah A1 - Jacobs, Heidi I. L. A1 - Van Diest, Ilse A1 - Schoenen, Jean A1 - Redgrave, Jessica A1 - Fang, Jiliang A1 - Deuchars, Jim A1 - Széles, Jozsef C. A1 - Thayer, Julian F. A1 - More, Kaushik A1 - Vonck, Kristl A1 - Steenbergen, Laura A1 - Vianna, Lauro C. A1 - McTeague, Lisa M. A1 - Ludwig, Mareike A1 - Veldhuizen, Maria G. A1 - De Couck, Marijke A1 - Casazza, Marina A1 - Keute, Marius A1 - Bikson, Marom A1 - Andreatta, Marta A1 - D'Agostini, Martina A1 - Weymar, Mathias A1 - Betts, Matthew A1 - Prigge, Matthias A1 - Kaess, Michael A1 - Roden, Michael A1 - Thai, Michelle A1 - Schuster, Nathaniel M. A1 - Montano, Nicola A1 - Hansen, Niels A1 - Kroemer, Nils B. A1 - Rong, Peijing A1 - Fischer, Rico A1 - Howland, Robert H. A1 - Sclocco, Roberta A1 - Sellaro, Roberta A1 - Garcia, Ronald G. A1 - Bauer, Sebastian A1 - Gancheva, Sofiya A1 - Stavrakis, Stavros A1 - Kampusch, Stefan A1 - Deuchars, Susan A. A1 - Wehner, Sven A1 - Laborde, Sylvain A1 - Usichenko, Taras A1 - Polak, Thomas A1 - Zaehle, Tino A1 - Borges, Uirassu A1 - Teckentrup, Vanessa A1 - Jandackova, Vera K. A1 - Napadow, Vitaly A1 - Koenig, Julian T1 - International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020) JF - Frontiers in Human Neuroscience N2 - Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. KW - transcutaneous vagus nerve stimulation KW - minimum reporting standards KW - guidelines & recommendations KW - transcutaneous auricular vagus nerve stimulation KW - transcutaneous cervical vagus nerve stimulation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234346 SN - 1662-5161 VL - 14 ER - TY - JOUR A1 - Biere, Silvia A1 - Kranz, Thorsten M. A1 - Matura, Silke A1 - Petrova, Kristiyana A1 - Streit, Fabian A1 - Chiocchetti, Andreas G. A1 - Grimm, Oliver A1 - Brum, Murielle A1 - Brunkhorst-Kanaan, Natalie A1 - Oertel, Viola A1 - Malyshau, Aliaksandr A1 - Pfennig, Andrea A1 - Bauer, Michael A1 - Schulze, Thomas G. A1 - Kittel-Schneider, Sarah A1 - Reif, Andreas T1 - Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults JF - Frontiers in Psychiatry N2 - Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD. Methods: A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes. Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls. Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification. KW - polygenic risk score KW - bipolar disorder KW - genetic phenotypes KW - depression KW - ADHD KW - early recognition Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214976 VL - 11 ER - TY - JOUR A1 - Neumann-Haefelin, D. A1 - Rethwilm, Axel A1 - Bauer, G. A1 - Gudat, F. A1 - zur Hausen, H. T1 - Characterization of a foamy virus isolated from Cercopithecus aethiops lymphoblastoid cells N2 - A virus derived from cells of a Iymphoblastoid line originating from the lymph node of a healthy African green monkey was characterized as a typical member of the foamy virus subgroup of rctroviridac by its morphological, physicochemical, biological and biochemical properties (reverse transcriptase actvity). Besides the usual host range of foamy viruses, the isolated strain revealed a remarkable T -lymphotropism, distinguishing it from the prototypes of foamy viruses previously isolated from African green monkeys. Two foamy virus infectious are demonstrated in human contacts of the African green monkey colony, with the animal barbauring the isolate. KW - Virologie Y1 - 1983 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61538 ER - TY - JOUR A1 - Keller, Andreas A1 - Leidinger, Petra A1 - Vogel, Britta A1 - Backes, Christina A1 - ElSharawy, Abdou A1 - Galata, Valentina A1 - Mueller, Sabine C. A1 - Marquart, Sabine A1 - Schrauder, Michael G. A1 - Strick, Reiner A1 - Bauer, Andrea A1 - Wischhusen, Jörg A1 - Beier, Markus A1 - Kohlhaas, Jochen A1 - Katus, Hugo A. A1 - Hoheisel, Jörg A1 - Franke, Andre A1 - Meder, Benjamin A1 - Meese, Eckart T1 - miRNAs can be generally associated with human pathologies as exemplified for miR-144* JF - BMC MEDICINE N2 - Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers. KW - peripheral blood KW - microna profiles KW - disease KW - signature KW - expression KW - miRNA KW - microarray KW - biomarker KW - bioinformatics KW - lung-cancer KW - multiple sclerosis KW - gene KW - serum Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114349 SN - 1741-7015 VL - 12 ER -