TY  - JOUR
A1  - Herzog, Katharina
A1  - Andreatta, Marta
A1  - Schneider, Kristina
A1  - Schiele, Miriam A.
A1  - Domschke, Katharina
A1  - Romanos, Marcel
A1  - Deckert, Jürgen
A1  - Pauli, Paul
T1  - Reducing Generalization of Conditioned Fear: Beneficial Impact of Fear Relevance and Feedback in Discrimination Training
JF  - Frontiers in Psychology
N2  - Anxiety patients over-generalize fear, possibly because of an incapacity to discriminate threat and safety signals. Discrimination trainings are promising approaches for reducing such fear over-generalization. Here we investigated the efficacy of a fear-relevant vs. a fear-irrelevant discrimination training on fear generalization and whether the effects are increased with feedback during training. Eighty participants underwent two fear acquisition blocks, during which one face (conditioned stimulus, CS+), but not another face (CS−), was associated with a female scream (unconditioned stimulus, US). During two generalization blocks, both CSs plus four morphs (generalization stimuli, GS1–GS4) were presented. Between these generalization blocks, half of the participants underwent a fear-relevant discrimination training (discrimination between CS+ and the other faces) with or without feedback and the other half a fear-irrelevant discrimination training (discrimination between the width of lines) with or without feedback. US expectancy, arousal, valence ratings, and skin conductance responses (SCR) indicated successful fear acquisition. Importantly, fear-relevant vs. fear-irrelevant discrimination trainings and feedback vs. no feedback reduced generalization as reflected in US expectancy ratings independently from one another. No effects of training condition were found for arousal and valence ratings or SCR. In summary, this is a first indication that fear-relevant discrimination training and feedback can improve the discrimination between threat and safety signals in healthy individuals, at least for learning-related evaluations, but not evaluations of valence or (physiological) arousal.
KW  - fear generalization
KW  - feedback
KW  - discrimination training
KW  - fear-relevant training
KW  - classical conditioning
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239970
SN  - 1664-1078
VL  - 12
ER  - 
TY  - JOUR
A1  - Busch, Martin
A1  - Nadal, Jennifer
A1  - Schmid, Matthias
A1  - Paul, Katharina
A1  - Titze, Stephanie
A1  - Hübner, Silvia
A1  - Köttgen, Anna
A1  - Schultheiss, Ulla T.
A1  - Baid-Agrawal, Seema
A1  - Lorenzen, Johan
A1  - Schlieper, Georg
A1  - Sommerer, Claudia
A1  - Krane, Vera
A1  - Hilge, Robert
A1  - Kielstein, Jan T.
A1  - Kronenberg, Florian
A1  - Wanner, Christoph
A1  - Eckardt, Kai-Uwe
A1  - Wolf, Gunter
T1  - Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort
JF  - BMC Nephrology
N2  - Background

Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD.

Methods

The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) between 30–60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure.

Results

At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25th–75th percentile: 6.8–7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 % CI 1.02–1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04–1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26–7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77–6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides.

Conclusions

Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.
KW  - Chronic kidney disease
KW  - Glycaemic control
KW  - Hemoglobin A1C
KW  - Insulin therapy
KW  - Oral antidiabetic drugs
KW  - Diabetes mellitus
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164687
VL  - 17
IS  - 59
ER  - 
TY  - JOUR
A1  - Vigorito, Elena
A1  - Kuchenbaecker, Karoline B.
A1  - Beesley, Jonathan
A1  - Adlard, Julian
A1  - Agnarsson, Bjarni A.
A1  - Andrulis, Irene L.
A1  - Arun, Banu K.
A1  - Barjhoux, Laure
A1  - Belotti, Muriel
A1  - Benitez, Javier
A1  - Berger, Andreas
A1  - Bojesen, Anders
A1  - Bonanni, Bernardo
A1  - Brewer, Carole
A1  - Caldes, Trinidad
A1  - Caligo, Maria A.
A1  - Campbell, Ian
A1  - Chan, Salina B.
A1  - Claes, Kathleen B. M.
A1  - Cohn, David E.
A1  - Cook, Jackie
A1  - Daly, Mary B.
A1  - Damiola, Francesca
A1  - Davidson, Rosemarie
A1  - de Pauw, Antoine
A1  - Delnatte, Capucine
A1  - Diez, Orland
A1  - Domchek, Susan M.
A1  - Dumont, Martine
A1  - Durda, Katarzyna
A1  - Dworniczak, Bernd
A1  - Easton, Douglas F.
A1  - Eccles, Diana
A1  - Ardnor, Christina Edwinsdotter
A1  - Eeles, Ros
A1  - Ejlertsen, Bent
A1  - Ellis, Steve
A1  - Evans, D. Gareth
A1  - Feliubadalo, Lidia
A1  - Fostira, Florentia
A1  - Foulkes, William D.
A1  - Friedman, Eitan
A1  - Frost, Debra
A1  - Gaddam, Pragna
A1  - Ganz, Patricia A.
A1  - Garber, Judy
A1  - Garcia-Barberan, Vanesa
A1  - Gauthier-Villars, Marion
A1  - Gehrig, Andrea
A1  - Gerdes, Anne-Marie
A1  - Giraud, Sophie
A1  - Godwin, Andrew K.
A1  - Goldgar, David E.
A1  - Hake, Christopher R.
A1  - Hansen, Thomas V. O.
A1  - Healey, Sue
A1  - Hodgson, Shirley
A1  - Hogervorst, Frans B. L.
A1  - Houdayer, Claude
A1  - Hulick, Peter J.
A1  - Imyanitov, Evgeny N.
A1  - Isaacs, Claudine
A1  - Izatt, Louise
A1  - Izquierdo, Angel
A1  - Jacobs, Lauren
A1  - Jakubowska, Anna
A1  - Janavicius, Ramunas
A1  - Jaworska-Bieniek, Katarzyna
A1  - Jensen, Uffe Birk
A1  - John, Esther M.
A1  - Vijai, Joseph
A1  - Karlan, Beth Y.
A1  - Kast, Karin
A1  - Khan, Sofia
A1  - Kwong, Ava
A1  - Laitman, Yael
A1  - Lester, Jenny
A1  - Lesueur, Fabienne
A1  - Liljegren, Annelie
A1  - Lubinski, Jan
A1  - Mai, Phuong L.
A1  - Manoukian, Siranoush
A1  - Mazoyer, Sylvie
A1  - Meindl, Alfons
A1  - Mensenkamp, Arjen R.
A1  - Montagna, Marco
A1  - Nathanson, Katherine L.
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Niederacher, Dieter
A1  - Olah, Edith
A1  - Olopade, Olufunmilayo I.
A1  - Ong, Kai-ren
A1  - Osorio, Ana
A1  - Park, Sue Kyung
A1  - Paulsson-Karlsson, Ylva
A1  - Pedersen, Inge Sokilde
A1  - Peissel, Bernard
A1  - Peterlongo, Paolo
A1  - Pfeiler, Georg
A1  - Phelan, Catherine M.
A1  - Piedmonte, Marion
A1  - Poppe, Bruce
A1  - Pujana, Miquel Angel
A1  - Radice, Paolo
A1  - Rennert, Gad
A1  - Rodriguez, Gustavo C.
A1  - Rookus, Matti A.
A1  - Ross, Eric A.
A1  - Schmutzler, Rita Katharina
A1  - Simard, Jacques
A1  - Singer, Christian F.
A1  - Slavin, Thomas P.
A1  - Soucy, Penny
A1  - Southey, Melissa
A1  - Steinemann, Doris
A1  - Stoppa-Lyonnet, Dominique
A1  - Sukiennicki, Grzegorz
A1  - Sutter, Christian
A1  - Szabo, Csilla I.
A1  - Tea, Muy-Kheng
A1  - Teixeira, Manuel R.
A1  - Teo, Soo-Hwang
A1  - Terry, Mary Beth
A1  - Thomassen, Mads
A1  - Tibiletti, Maria Grazia
A1  - Tihomirova, Laima
A1  - Tognazzo, Silvia
A1  - van Rensburg, Elizabeth J.
A1  - Varesco, Liliana
A1  - Varon-Mateeva, Raymonda
A1  - Vratimos, Athanassios
A1  - Weitzel, Jeffrey N.
A1  - McGuffog, Lesley
A1  - Kirk, Judy
A1  - Toland, Amanda Ewart
A1  - Hamann, Ute
A1  - Lindor, Noralane
A1  - Ramus, Susan J.
A1  - Greene, Mark H.
A1  - Couch, Fergus J.
A1  - Offit, Kenneth
A1  - Pharoah, Paul D. P.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
T1  - Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
JF  - PLoS ONE
N2  - Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
KW  - fine-scale mapping
KW  - ovarian cancer
KW  - genetics
KW  - BRCA1
KW  - BRCA2
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166869
VL  - 11
IS  - 7
ER  - 
TY  - JOUR
A1  - Couch, Fergus J.
A1  - Wang, Xianshu
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Olswold, Curtis
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Fredericksen, Zachary
A1  - Barrowdale, Daniel
A1  - Dennis, Joe
A1  - Gaudet, Mia M.
A1  - Dicks, Ed
A1  - Kosel, Matthew
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Lee, Adam
A1  - Bacot, Françios
A1  - Vincent, Daniel
A1  - Hogervorst, Frans B. L.
A1  - Peock, Susan
A1  - Stoppa-Lyonnet, Dominique
A1  - Jakubowska, Anna
A1  - Radice, Paolo
A1  - Schmutzler, Rita Katharina
A1  - Domchek, Susan M.
A1  - Piedmonte, Marion
A1  - Singer, Christian F.
A1  - Friedman, Eitan
A1  - Thomassen, Mads
A1  - Hansen, Thomas V. O.
A1  - Neuhausen, Susan L.
A1  - Szabo, Csilla I.
A1  - Blanco, Ingnacio
A1  - Greene, Mark H.
A1  - Karlan, Beth Y.
A1  - Garber, Judy
A1  - Phelan, Catherine M.
A1  - Weitzel, Jeffrey N.
A1  - Montagna, Marco
A1  - Olah, Edith
A1  - Andrulis, Irene L.
A1  - Godwin, Andrew K.
A1  - Yannoukakos, Drakoulis
A1  - Goldgar, David E.
A1  - Caldes, Trinidad
A1  - Nevanlinna, Heli
A1  - Osorio, Ana
A1  - Terry, Mary Beth
A1  - Daly, Mary B.
A1  - van Rensburg, Elisabeth J.
A1  - Hamann, Ute
A1  - Ramus, Susan J.
A1  - Toland, Amanda Ewart
A1  - Caligo, Maria A.
A1  - Olopade, Olufunmilayo I.
A1  - Tung, Nadine
A1  - Claes, Kathleen
A1  - Beattie, Mary S.
A1  - Southey, Melissa C.
A1  - Imyanitov, Evgeny N.
A1  - Tischkowitz, Marc
A1  - Janavicius, Ramunas
A1  - John, Esther M.
A1  - Kwong, Ava
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Balmaña, Judith
A1  - Barkardottir, Rosa B.
A1  - Arun, Banu K.
A1  - Rennert, Gad
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Campbell, Ian
A1  - van der Hout, Annemarie H.
A1  - van Deurzen, Carolien H. M.
A1  - Seynaeve, Caroline
A1  - Garcia, Encarna B. Gómez
A1  - van Leeuwen, Flora E.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Gille, Johannes J. P.
A1  - Ausems, Magreet G. E. M.
A1  - Blok, Marinus J.
A1  - Ligtenberg, Marjolinjin J. L.
A1  - Rookus, Matti A.
A1  - Devilee, Peter
A1  - Verhoef, Senno
A1  - van Os, Theo A. M.
A1  - Wijnen, Juul T.
A1  - Frost, Debra
A1  - Ellis, Steve
A1  - Fineberg, Elena
A1  - Platte, Radke
A1  - Evans, D. Gareth
A1  - Izatt, Luise
A1  - Eeles, Rosalind A.
A1  - Adlard, Julian
A1  - Eccles, Diana M.
A1  - Cook, Jackie
A1  - Brewer, Carole
A1  - Douglas, Fiona
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Side, Lucy E.
A1  - Donaldson, Alan
A1  - Houghton, Catherine
A1  - Rogers, Mark T.
A1  - Dorkins, Huw
A1  - Eason, Jacqueline
A1  - Gregory, Helen
A1  - McCann, Emma
A1  - Murray, Alex
A1  - Calender, Alain
A1  - Hardouin, Agnès
A1  - Berthet, Pascaline
A1  - Delnatte, Capucine
A1  - Nogues, Catherine
A1  - Lasset, Christine
A1  - Houdayer, Claude
A1  - Leroux,, Dominique
A1  - Rouleau, Etienne
A1  - Prieur, Fabienne
A1  - Damiola, Francesca
A1  - Sobol, Hagay
A1  - Coupier, Isabelle
A1  - Venat-Bouvet, Laurence
A1  - Castera, Laurent
A1  - Gauthier-Villars, Marion
A1  - Léoné, Mélanie
A1  - Pujol, Pascal
A1  - Mazoyer, Sylvie
A1  - Bignon, Yves-Jean
A1  - Zlowocka-Perlowska, Elzbieta
A1  - Gronwald, Jacek
A1  - Lubinski,, Jan
A1  - Durda, Katarzyna
A1  - Jaworska, Katarzyna
A1  - Huzarski, Tomasz
A1  - Spurdle, Amanda B.
A1  - Viel, Alessandra
A1  - Peissel, Bernhard
A1  - Bonanni, Bernardo
A1  - Melloni, Guilia
A1  - Ottini, Laura
A1  - Papi, Laura
A1  - Varesco, Liliana
A1  - Tibiletti, Maria Grazia
A1  - Peterlongo, Paolo
A1  - Volorio, Sara
A1  - Manoukian, Siranoush
A1  - Pensotti, Valeria
A1  - Arnold, Norbert
A1  - Engel, Christoph
A1  - Deissler, Helmut
A1  - Gadzicki, Dorothea
A1  - Gehrig, Andrea
A1  - Kast, Karin
A1  - Rhiem, Kerstin
A1  - Meindl, Alfons
A1  - Niederacher, Dieter
A1  - Ditsch, Nina
A1  - Plendl, Hansjoerg
A1  - Preisler-Adams, Sabine
A1  - Engert, Stefanie
A1  - Sutter, Christian
A1  - Varon-Mateeva, Raymenda
A1  - Wappenschmidt, Barbara
A1  - Weber, Bernhard H. F.
A1  - Arver, Brita
A1  - Stenmark-Askmalm, Marie
A1  - Loman, Niklas
A1  - Rosenquist, Richard
A1  - Einbeigi, Zakaria
A1  - Nathanson, Katherine L.
A1  - Rebbeck, Timothy R.
A1  - Blank, Stephanie V.
A1  - Cohn, David E.
A1  - Rodriguez, Gustavo C.
A1  - Small, Laurie
A1  - Friedlander, Michael
A1  - Bae-Jump, Victoria L.
A1  - Fink-Retter, Anneliese
A1  - Rappaport, Christine
A1  - Gschwantler-Kaulich, Daphne
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Lindor, Noralane M.
A1  - Kaufman, Bella
A1  - Paluch, Shani Shimon
A1  - Laitman, Yael
A1  - Skytte, Anne-Bine
A1  - Gerdes, Anne-Marie
A1  - Pedersen, Inge Sokilde
A1  - Moeller, Sanne Traasdahl
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Vijai, Joseph
A1  - Sarrel, Kara
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Ozcelik, Hilmi
A1  - Ejlertsen, Bent
A1  - Nielsen, Finn C.
A1  - Jønson, Lars
A1  - Andersen, Mette K.
A1  - Ding, Yuan Chun
A1  - Steele, Linda
A1  - Foretova, Lenka
A1  - Teulé, Alex
A1  - Lazaro, Conxi
A1  - Brunet, Joan
A1  - Pujana, Miquel Angel
A1  - Mai, Phuong L.
A1  - Loud, Jennifer T.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - Orsulic, Sandra
A1  - Narod, Steven A.
A1  - Herzog, Josef
A1  - Sand, Sharon R.
A1  - Tognazzo, Silvia
A1  - Agata, Simona
A1  - Vaszko, Tibor
A1  - Weaver, Joellen
A1  - Stravropoulou, Alexandra V.
A1  - Buys, Saundra S.
A1  - Romero, Atocha
A1  - de la Hoya, Miguel
A1  - Aittomäki, Kristiina
A1  - Muranen, Taru A.
A1  - Duran, Mercedes
A1  - Chung, Wendy K.
A1  - Lasa, Adriana
A1  - Dorfling, Cecilia M.
A1  - Miron, Alexander
A1  - Benitez, Javier
A1  - Senter, Leigha
A1  - Huo, Dezheng
A1  - Chan, Salina B.
A1  - Sokolenko, Anna P.
A1  - Chiquette, Jocelyne
A1  - Tihomirova, Laima
A1  - Friebel, Tara M.
A1  - Agnarsson, Bjarne A.
A1  - Lu, Karen H.
A1  - Lejbkowicz, Flavio
A1  - James, Paul A.
A1  - Hall, Per
A1  - Dunning, Alison M.
A1  - Tessier, Daniel
A1  - Cunningham, Julie
A1  - Slager, Susan L.
A1  - Chen, Wang
A1  - Hart, Steven
A1  - Stevens, Kristen
A1  - Simard, Jacques
A1  - Pastinen, Tomi
A1  - Pankratz, Vernon S.
A1  - Offit, Kenneth
A1  - Easton, Douglas F.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
T1  - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
JF  - PLOS Genetics
N2  - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
KW  - common variants
KW  - susceptibility alleles
KW  - genetic variants
KW  - modifiers
KW  - ZNF365
KW  - investigators
KW  - population
KW  - consortium
KW  - selection
KW  - subtypes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947
SN  - 1553-7404
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Schwarz, Katharina A.
A1  - Wieser, Matthias J.
A1  - Gerdes, Antje B. M.
A1  - Mühlberger, Andreas
A1  - Pauli, Paul
T1  - Why are you looking like that? How the context influences evaluation and processing of human faces
JF  - Social Cognitive and Affective Neuroscience
N2  - Perception and evaluation of facial expressions are known to be heavily modulated by emotional features of contextual information. Such contextual effects, however, might also be driven by non-emotional aspects of contextual information, an interaction of emotional and non-emotional factors, and by the observers’ inherent traits. Therefore, we sought to assess whether contextual information about self-reference in addition to information about valence influences the evaluation and neural processing of neutral faces. Furthermore, we investigated whether social anxiety moderates these effects. In the present functional magnetic resonance imaging (fMRI) study, participants viewed neutral facial expressions preceded by a contextual sentence conveying either positive or negative evaluations about the participant or about somebody else. Contextual influences were reflected in rating and fMRI measures, with strong effects of self-reference on brain activity in the medial prefrontal cortex and right fusiform gyrus. Additionally, social anxiety strongly affected the response to faces conveying negative, self-related evaluations as revealed by the participants’ rating patterns and brain activity in cortical midline structures and regions of interest in the left and right middle frontal gyrus. These results suggest that face perception and processing are highly individual processes influenced by emotional and non-emotional aspects of contextual information and further modulated by individual personality traits.
KW  - social anxiety
KW  - facial expression
KW  - context
KW  - self-reference
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132126
VL  - 8
IS  - 4
ER  - 
TY  - JOUR
A1  - Klauke, Benedikt
A1  - Winter, Bernward
A1  - Gajewska, Agnes
A1  - Zwanzger, Peter
A1  - Reif, Andreas
A1  - Herrmann, Martin J.
A1  - Dlugos, Andrea
A1  - Warrings, Bodo
A1  - Jacob, Christian
A1  - Mühlberger, Andreas
A1  - Arolt, Volker
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
T1  - Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma
JF  - PLoS One
N2  - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.
KW  - COMT VAL(158)MET polymorphism
KW  - serotonin transporter gene
KW  - life events
KW  - community sample
KW  - acoustic startle
KW  - prepulse inhibition
KW  - panic disorder
KW  - caffeine-induced anxiety
KW  - fear-potentiated startle
KW  - posttraumatic-stress-disorder
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132184
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Weber, Heike
A1  - Scholz, Claus Jürgen
A1  - Domschke, Katharina
A1  - Baumann, Christian
A1  - Klauke, Benedikt
A1  - Jacob, Christian P.
A1  - Maier, Wolfgang
A1  - Fritze, Jürgen
A1  - Bandelow, Borwin
A1  - Zwanzger, Peter Michael
A1  - Lang, Thomas
A1  - Fehm, Lydia
A1  - Ströhle, Andreas
A1  - Hamm, Alfons
A1  - Gerlach, Alexander L.
A1  - Alpers, Georg W.
A1  - Kircher, Tilo
A1  - Wittchen, Hans-Ulrich
A1  - Arolt, Volker
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Reif, Andreas
T1  - Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder
N2  - Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype6gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype6gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75830
ER  - 
TY  - JOUR
A1  - Lichter, Katharina
A1  - Paul, Mila Marie
A1  - Pauli, Martin
A1  - Schoch, Susanne
A1  - Kollmannsberger, Philip
A1  - Stigloher, Christian
A1  - Heckmann, Manfred
A1  - Sirén, Anna-Leena
T1  - Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse
JF  - Cell Reports
N2  - Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{−/−}\) and wild-type mice. In RIM1α\(^{−/−}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0–2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{−/−}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.
KW  - active zone
KW  - acute brain slices
KW  - CA3
KW  - electron tomography
KW  - high-pressure freezing
KW  - hippocampal mossy fiber bouton
KW  - RIM1α
KW  - SV pool
KW  - synaptic ultrastructure
KW  - presynaptic
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300913
VL  - 40
IS  - 12
ER  - 
TY  - JOUR
A1  - Pittig, Andre
A1  - Heinig, Ingmar
A1  - Goerigk, Stephan
A1  - Thiel, Freya
A1  - Hummel, Katrin
A1  - Scholl, Lucie
A1  - Deckert, Jürgen
A1  - Pauli, Paul
A1  - Domschke, Katharina
A1  - Lueken, Ulrike
A1  - Fydrich, Thomas
A1  - Fehm, Lydia
A1  - Plag, Jens
A1  - Ströhle, Andreas
A1  - Kircher, Tilo
A1  - Straube, Benjamin
A1  - Rief, Winfried
A1  - Koelkebeck, Katja
A1  - Arolt, Volker
A1  - Dannlowski, Udo
A1  - Margraf, Jürgen
A1  - Totzeck, Christina
A1  - Schneider, Silvia
A1  - Neudeck, Peter
A1  - Craske, Michelle G.
A1  - Hollandt, Maike
A1  - Richter, Jan
A1  - Hamm, Alfons
A1  - Wittchen, Hans-Ulrich
T1  - Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial
JF  - Depression and Anxiety
N2  - Background

The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.

Methods

This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression.

Results

Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse.

Conclusions

Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.
KW  - randomized controlled trial
KW  - anxiety disorders
KW  - exposure therapy
KW  - intensified treatment
KW  - public health
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257331
VL  - 38
IS  - 11
ER  - 
TY  - JOUR
A1  - Rayner, Christopher
A1  - Coleman, Jonathan R. I.
A1  - Purves, Kirstin L.
A1  - Hodsoll, John
A1  - Goldsmith, Kimberley
A1  - Alpers, Georg W.
A1  - Andersson, Evelyn
A1  - Arolt, Volker
A1  - Boberg, Julia
A1  - Bögels, Susan
A1  - Creswell, Cathy
A1  - Cooper, Peter
A1  - Curtis, Charles
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
A1  - El Alaoui, Samir
A1  - Fehm, Lydia
A1  - Fydrich, Thomas
A1  - Gerlach, Alexander L.
A1  - Grocholewski, Anja
A1  - Hahlweg, Kurt
A1  - Hamm, Alfons
A1  - Hedman, Erik
A1  - Heiervang, Einar R.
A1  - Hudson, Jennifer L.
A1  - Jöhren, Peter
A1  - Keers, Robert
A1  - Kircher, Tilo
A1  - Lang, Thomas
A1  - Lavebratt, Catharina
A1  - Lee, Sang-hyuck
A1  - Lester, Kathryn J.
A1  - Lindefors, Nils
A1  - Margraf, Jürgen
A1  - Nauta, Maaike
A1  - Pané-Farré, Christiane A.
A1  - Pauli, Paul
A1  - Rapee, Ronald M.
A1  - Reif, Andreas
A1  - Rief, Winfried
A1  - Roberts, Susanna
A1  - Schalling, Martin
A1  - Schneider, Silvia
A1  - Silverman, Wendy K.
A1  - Ströhle, Andreas
A1  - Teismann, Tobias
A1  - Thastum, Mikael
A1  - Wannemüller, Andre
A1  - Weber, Heike
A1  - Wittchen, Hans-Ulrich
A1  - Wolf, Christiane
A1  - Rück, Christian
A1  - Breen, Gerome
A1  - Eley, Thalia C.
T1  - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
JF  - Translational Psychiatry
N2  - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
KW  - Human behaviour
KW  - Personalized medicine
KW  - Prognostic markers
KW  - Psychiatric disorders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225048
VL  - 9
IS  - 150
ER  - 
TY  - JOUR
A1  - Schiele, Miriam A.
A1  - Ziegler, Christiane
A1  - Kollert, Leonie
A1  - Katzorke, Andrea
A1  - Schartner, Christoph
A1  - Busch, Yasmin
A1  - Gromer, Daniel
A1  - Reif, Andreas
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Herrmann, Martin J.
A1  - Domschke, Katharina
T1  - Plasticity of Functional MAOA Gene Methylation in Acrophobia
JF  - International Journal of Neuropsychopharmacology
N2  - Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.
KW  - monoamine oxidase A
KW  - anxiety
KW  - extinction
KW  - epigenetics
KW  - DNA methylation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228571
VL  - 21
IS  - 9
ER  - 
TY  - JOUR
A1  - Grubisic, Maja
A1  - Haim, Abraham
A1  - Bhusal, Pramod
A1  - Dominoni, Davide M.
A1  - Gabriel, Katharina M. A.
A1  - Jechow, Andreas
A1  - Kupprat, Franziska
A1  - Lerner, Amit
A1  - Marchant, Paul
A1  - Riley, William
A1  - Stebelova, Katarina
A1  - van Grunsven, Roy H. A.
A1  - Zeman, Michal
A1  - Zubidat, Abed E.
A1  - Hölker, Franz
T1  - Light Pollution, Circadian Photoreception, and Melatonin in Vertebrates
JF  - Sustainability
N2  - Artificial light at night (ALAN) is increasing exponentially worldwide, accelerated by the transition to new efficient lighting technologies. However, ALAN and resulting light pollution can cause unintended physiological consequences. In vertebrates, production of melatonin—the “hormone of darkness” and a key player in circadian regulation—can be suppressed by ALAN. In this paper, we provide an overview of research on melatonin and ALAN in vertebrates. We discuss how ALAN disrupts natural photic environments, its effect on melatonin and circadian rhythms, and different photoreceptor systems across vertebrate taxa. We then present the results of a systematic review in which we identified studies on melatonin under typical light-polluted conditions in fishes, amphibians, reptiles, birds, and mammals, including humans. Melatonin is suppressed by extremely low light intensities in many vertebrates, ranging from 0.01–0.03 lx for fishes and rodents to 6 lx for sensitive humans. Even lower, wavelength-dependent intensities are implied by some studies and require rigorous testing in ecological contexts. In many studies, melatonin suppression occurs at the minimum light levels tested, and, in better-studied groups, melatonin suppression is reported to occur at lower light levels. We identify major research gaps and conclude that, for most groups, crucial information is lacking. No studies were identified for amphibians and reptiles and long-term impacts of low-level ALAN exposure are unknown. Given the high sensitivity of vertebrate melatonin production to ALAN and the paucity of available information, it is crucial to research impacts of ALAN further in order to inform effective mitigation strategies for human health and the wellbeing and fitness of vertebrates in natural ecosystems.
KW  - ALAN
KW  - artificial light at night
KW  - biological rhythm
KW  - circadian rhythm
KW  - melatonin
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193095
SN  - 2071-1050
VL  - 11
IS  - 22
ER  - 
TY  - JOUR
A1  - Bäuerlein, Carina A.
A1  - Qureischi, Musga
A1  - Mokhtari, Zeinab
A1  - Tabares, Paula
A1  - Brede, Christian
A1  - Jordán Garrote, Ana-Laura
A1  - Riedel, Simone S.
A1  - Chopra, Martin
A1  - Reu, Simone
A1  - Mottok, Anja
A1  - Arellano-Viera, Estibaliz
A1  - Graf, Carolin
A1  - Kurzwart, Miriam
A1  - Schmiedgen, Katharina
A1  - Einsele, Hermann
A1  - Wölfl, Matthias
A1  - Schlegel, Paul-Gerhardt
A1  - Beilhack, Andreas
T1  - A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease
JF  - Frontiers in Immunology
N2  - Acute graft-versus-host disease (aGvHD) is a severe and often life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). AGvHD is mediated by alloreactive donor T-cells targeting predominantly the gastrointestinal tract, liver, and skin. Recent work in mice and patients undergoing allo-HCT showed that alloreactive T-cells can be identified by the expression of α4β7 integrin on T-cells even before manifestation of an aGvHD. Here, we investigated whether the detection of a combination of the expression of T-cell surface markers on peripheral blood (PB) CD8\(^+\) T-cells would improve the ability to predict aGvHD. To this end, we employed two independent preclinical models of minor histocompatibility antigen mismatched allo-HCT following myeloablative conditioning. Expression profiles of integrins, selectins, chemokine receptors, and activation markers of PB donor T-cells were measured with multiparameter flow cytometry at multiple time points before the onset of clinical aGvHD symptoms. In both allo-HCT models, we demonstrated a significant upregulation of α4β7 integrin, CD162E, CD162P, and conversely, a downregulation of CD62L on donor T-cells, which could be correlated with the development of aGvHD. Other surface markers, such as CD25, CD69, and CC-chemokine receptors were not found to be predictive markers. Based on these preclinical data from mouse models, we propose a surface marker panel on peripheral blood T-cells after allo-HCT combining α4β7 integrin with CD62L, CD162E, and CD162P (cutaneous lymphocyte antigens, CLA, in humans) to identify patients at risk for developing aGvHD early after allo-HCT.
KW  - acute graft-versus-host disease
KW  - alloreactive T cells
KW  - transplantation
KW  - prediction
KW  - mouse models
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224290
SN  - 1664-3224
VL  - 11
ER  - 
TY  - JOUR
A1  - Ziegler, Georg C.
A1  - Ehlis, Ann-Christine
A1  - Weber, Heike
A1  - Vitale, Maria Rosaria
A1  - Zöller, Johanna E. M.
A1  - Ku, Hsing-Ping
A1  - Schiele, Miriam A.
A1  - Kürbitz, Laura I.
A1  - Romanos, Marcel
A1  - Pauli, Paul
A1  - Kalisch, Raffael
A1  - Zwanzger, Peter
A1  - Domschke, Katharina
A1  - Fallgatter, Andreas J.
A1  - Reif, Andreas
A1  - Lesch, Klaus-Peter
T1  - A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
JF  - Genes
N2  - The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
KW  - ADHD
KW  - CDH13
KW  - neurodevelopment
KW  - executive functions
KW  - working memory
KW  - Big Five
KW  - agreeableness
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245220
SN  - 2073-4425
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Schiele, Miriam A.
A1  - Reinhard, Julia
A1  - Reif, Andreas
A1  - Domschke, Katharina
A1  - Romanos, Marcel
A1  - Deckert, Jürgen
A1  - Pauli, Paul
T1  - Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults
JF  - Developmental Psychobiology
N2  - Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.
KW  - fear conditioning
KW  - fear generalization
KW  - development
KW  - skin conductance
KW  - maturation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189488
VL  - 58
IS  - 4
ER  - 
TY  - JOUR
A1  - Kuhn, Manuel
A1  - Scharfenort, Robert
A1  - Schümann, Dirk
A1  - Schiele, Miriam A.
A1  - Münsterkötter, Anna L.
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
A1  - Haaker, Jan
A1  - Kalisch, Raffael
A1  - Pauli, Paul
A1  - Reif, Andreas
A1  - Romanos, Marcel
A1  - Zwanzger, Peter
A1  - Lonsdorf, Tina B.
T1  - Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament
JF  - Social Cognitive and Affective Neuroscience
N2  - Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.
KW  - VBM
KW  - childhood maltreatment
KW  - adversity
KW  - stressful life events
KW  - mismatch
KW  - allostatic load
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189645
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Herzberg, Moritz
A1  - Scherling, Korbinian
A1  - Stahl, Robert
A1  - Tiedt, Steffen
A1  - Wollenweber, Frank A.
A1  - Küpper, Clemens
A1  - Feil, Katharina
A1  - Forbrig, Robert
A1  - Patzig, Maximilian
A1  - Kellert, Lars
A1  - Kunz, Wolfgang G.
A1  - Reidler, Paul
A1  - Zimmermann, Hanna
A1  - Liebig, Thomas
A1  - Dieterich, Marianne
A1  - Dorn, Franziska
T1  - Late Thrombectomy in Clinical Practice: Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry
JF  - Clinical Neuroradiology
N2  - Background and Purpose
To provide real-world data on outcome and procedural factors of late thrombectomy patients.

Methods
We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2).

Results
Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes.

Conclusion
In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.
KW  - late thrombectomy
KW  - stroke
KW  - endovascular therapy
KW  - outcome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264765
VL  - 31
IS  - 3
ER  - 
TY  - JOUR
A1  - Hein, Grit
A1  - Gamer, Matthias
A1  - Gall, Dominik
A1  - Gründahl, Marthe
A1  - Domschke, Katharina
A1  - Andreatta, Marta
A1  - Wieser, Matthias J.
A1  - Pauli, Paul
T1  - Social cognitive factors outweigh negative emotionality in predicting COVID-19 related safety behaviors
JF  - Preventive Medicine Reports
N2  - Emotion-motivation models propose that behaviors, including health behaviors, should be predicted by the same variables that also predict negative affect since emotional reactions should induce a motivation to avoid threatening situations. In contrast, social cognitive models propose that safety behaviors are predicted by a different set of variables that mainly reflect cognitive and socio-structural aspects. Here, we directly tested these opposing hypotheses in young adults (N = 4134) in the context of COVID-19-related safety behaviors to prevent infections. In each participant, we collected measures of negative affect as well as cognitive and socio-structural variables during the lockdown in the first infection wave in Germany. We found a negative effect of the pandemic on emotional responses. However, this was not the main predictor for young adults’ willingness to comply with COVID-19-related safety measures. Instead, individual differences in compliance were mainly predicted by cognitive and socio-structural variables. These results were confirmed in an independent data set. This study shows that individuals scoring high on negative affect during the pandemic are not necessarily more likely to comply with safety regulations. Instead, political measures should focus on cognitive interventions and the societal relevance of the health issue. These findings provide important insights into the basis of health-related concerns and feelings as well as behavioral adaptations.
KW  - social cognitive
KW  - negative affect
KW  - safety behavior
KW  - survey
KW  - COVID-19
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265008
VL  - 24
ER  - 
TY  - JOUR
A1  - Ruf, Katharina
A1  - Badran, Alaa
A1  - Siauw, Céline
A1  - Haubitz, Imme
A1  - Schlegel, Paul-Gerhardt
A1  - Hebestreit, Helge
A1  - Härtel, Christoph
A1  - Wiegering, Verena
T1  - Does allogeneic stem cell transplantation in survivors of pediatric leukemia impact regular physical activity, pulmonary function, and exercise capacity?
JF  - Molecular and Cellular Pediatrics
N2  - Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved survival in high-risk childhood leukemia but is associated with long-term sequelae such as impaired pulmonary function and reduced exercise capacity impacting quality of life.

Methods
A convenience sample of 17 patients after allo-HSCT (HSCT—12 male, age 15.7±6.7 years, time after HSCT 5.3±2.8 years) underwent pulmonary function testing, echocardiography, and an incremental exercise test on a bike. Physical activity and health-related quality of life were assessed by questionnaires (7-day physical activity recall, PEDS-QL). Seventeen healthy age- and gender-matched controls served as control group (CG) for results of pulmonary function and exercise testing.

Results
HSCT showed reduced pulmonary function (HSCT vs. CG: FEV1 90.5±14.0 vs. 108.0±8.7%pred; FVC 88.4±19.3 vs. 107.6±6.9%pred, DLCO 75.3±23.6 vs. 104.9±12.8%pred) and exercise capacity (VO2peak 89±30.8%pred, CG 98±17.5%pred; Wmax 84±21.7%pred, CG 115±22.8%pred), but no relevant cardiac dysfunction and a good quality of life (PEDS-QL mean overall score 83.3±10.7). Differences in peak oxygen uptake between groups were mostly explained by 5 adolescent patients who underwent total body irradiation for conditioning. They showed significantly reduced diffusion capacity and reduced peak oxygen uptake.

Patients reported a mean time of inactivity of 777±159min/day, moderate activity of 110±107 min/day, hard activity of 35±36 min/day, and very hard activity of 23±22 min/day. A higher amount of inactivity was associated with a lower peak oxygen uptake (correlation coefficient tau −0.48, p=0.023).

Conclusions
This pilot study shows that although patients after allo-HSCT reported a good quality of life, regular physical activity and exercise capacity are reduced in survivors of stem cell transplantation, especially in adolescents who are treated with total body irradiation for conditioning. Factors hindering regular physical activity need to be identified and exercise counseling should be part of follow-up visits in these patients.
KW  - childhood leukemia
KW  - exercise tolerance
KW  - physical activity
KW  - pediatric stem cell transplantation
KW  - exercise testing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265528
VL  - 8
ER  - 
TY  - JOUR
A1  - Mrestani, Achmed
A1  - Lichter, Katharina
A1  - Sirén, Anna-Leena
A1  - Heckmann, Manfred
A1  - Paul, Mila M.
A1  - Pauli, Martin
T1  - Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation
JF  - International Journal of Molecular Sciences
N2  - Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations.
KW  - active zone
KW  - nanotopology
KW  - neuromuscular junction
KW  - high-pressure freezing/freeze substitution
KW  - PFA in ethanol
KW  - dSTORM
KW  - Drosophila melanogaster
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304904
SN  - 1422-0067
VL  - 24
IS  - 3
ER  -