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265 Publications visible to you, out of a total of 265
BDNF as a biomarker for successful treatment of mood disorders: a systematic & quantitative meta-analysis.
LIFE Adult

Abstract (Expand)

BACKGROUND: Peripheral brain-derived neurotrophic factor (BDNF) is decreased in acute major depressive disorder (MDD) and bipolar disorder (BD) and recovered after treatment. Here we validated on a … meta-analytical level whether BDNF restores differentially according to treatment response and whose measurements could be used as a biomarker, plasma or serum. METHODS: Using strict inclusion criteria, we compared BDNF in healthy controls and patients with MDD (38 studies, n=6619), and BD (17 studies, n=1447). Pre- and post-treatment BDNF levels were meta-analyzed according to treatment response in patients from 21 MDD studies (n=735) and 7 BD studies (n=88). Serum and plasma subgroups were analyzed, publication bias was assessed and heterogeneity was investigated. RESULTS: Serum and plasma BDNF were decreased in acute MDD and BD, and did not differ in euthymia in comparison with control subjects. Antidepressive treatment increased serum BDNF levels in MDD in responders (Cohens d (d)=1.27, p=4.4E-07) and remitters (d=0.89, p=0.01), significantly more than in non-responders (d=0.11, p=0.69). For plasma BDNF in MDD and for BD, the evidence was insufficient for a meta-analysis. Although no significant difference was found between serum and plasma ES, variance of plasma ES was higher. LIMITATIONS: Between-study heterogeneity was explained only partially; signs of publication bias in serum studies. CONCLUSION: Serum BDNF might be regarded as a biomarker for the successful treatment of MDD. Serum measurements seem more reliable than plasma ones. Further research should focus on defining optimal time points for BDNF measurements and increase evidence for the usage of BDNF as a predictive biomarker in BD.

Authors: M. Polyakova, K. Stuke, K. Schuemberg, K. Mueller, P. Schoenknecht, M. L. Schroeter

Date Published: 15th Mar 2015

Publication Type: Not specified

Human Diseases: mental depression, bipolar disorder

Progesterone mediates brain functional connectivity changes during the menstrual cycle-a pilot resting state MRI study.
LIFE Adult

Abstract (Expand)

The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual … dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC) mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal Resting-state functional Magnetic Resonance Imaging (rs-fMRI) design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.

Authors: K. Arelin, K. Mueller, C. Barth, P. V. Rekkas, J. Kratzsch, I. Burmann, A. Villringer, J. Sacher

Date Published: 11th Mar 2015

Publication Type: Not specified

Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods.
LIFE Adult

Abstract (Expand)

Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal … experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.

Authors: C. Barth, A. Villringer, J. Sacher

Date Published: 10th Mar 2015

Publication Type: Not specified

Reference intervals for leukocyte subsets in adults: Results from a population-based study using 10-color flow cytometry.
LIFE Adult

Abstract (Expand)

BACKGROUND: Reference intervals for leukocyte subsets from peripheral blood are helpful for the understanding of disease states and therapy effects. METHODS: We performed in-depth immunophenotyping for … 608 healthy German adults from the Leipzig region from 40 to 79 years by 10-color flow cytometry (FCM) to gain reference information for various leukocyte subsets including subsets of granulocytes, monocytes and lymphocytes. RESULTS: First, we derived gender- and age-specific reference intervals for males and females from 40 to 59 and from 60 to 79 years, respectively. Second, we further investigated the influence of gender and age on leukocyte counts. We found significantly higher cell counts for monocytes (P < 0.001) and NK cells (P < 0.001) in men, whereas women had higher counts for B cells (P < 0.001), Th cells (P < 0.001) and regulatory T cells (P = 0.008). Furthermore, with increasing age, a decrease in Tc cells (about 8% within 5 years) and an increase in NK cells (<4% within 5 years) were observed. CONCLUSION: In future research, it should be investigated whether these are real ageing effects that can be confirmed in longitudinal studies. Furthermore, it is important to understand if the Tc cell count drop is functionally compensated by the increase of NK cells.

Authors: S. Melzer, S. Zachariae, J. Bocsi, C. Engel, M. Loffler, A. Tarnok

Date Published: 24th Feb 2015

Publication Type: Not specified

Identification of six new susceptibility loci for invasive epithelial ovarian cancer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation … carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P \textless 5 \times 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Authors: Karoline B. Kuchenbaecker, Susan J. Ramus, Jonathan Tyrer, Andrew Lee, Howard C. Shen, Jonathan Beesley, Kate Lawrenson, Lesley McGuffog, Sue Healey, Janet M. Lee, Tassja J. Spindler, Yvonne G. Lin, Tanja Pejovic, Yukie Bean, Qiyuan Li, Simon Coetzee, Dennis Hazelett, Alexander Miron, Melissa Southey, Mary Beth Terry, David E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Cecilia M. Dorfling, Elizabeth J. van Rensburg, Susan L. Neuhausen, Yuan Chun Ding, Thomas v. O. Hansen, Lars Jønson, Anne-Marie Gerdes, Bent Ejlertsen, Daniel Barrowdale, Joe Dennis, Javier Benitez, Ana Osorio, Maria Jose Garcia, Ian Komenaka, Jeffrey N. Weitzel, Pamela Ganschow, Paolo Peterlongo, Loris Bernard, Alessandra Viel, Bernardo Bonanni, Bernard Peissel, Siranoush Manoukian, Paolo Radice, Laura Papi, Laura Ottini, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Debra Frost, Jo Perkins, Radka Platte, Steve Ellis, Andrew K. Godwin, Rita Katharina Schmutzler, Alfons Meindl, Christoph Engel, Christian Sutter, Olga M. Sinilnikova, Francesca Damiola, Sylvie Mazoyer, Dominique Stoppa-Lyonnet, Kathleen Claes, Kim de Leeneer, Judy Kirk, Gustavo C. Rodriguez, Marion Piedmonte, David M. O’Malley, Miguel de La Hoya, Trinidad Caldes, Kristiina Aittomäki, Heli Nevanlinna, J. Margriet Collée, Matti A. Rookus, Jan C. Oosterwijk, Laima Tihomirova, Nadine Tung, Ute Hamann, Claudine Isaccs, Marc Tischkowitz, Evgeny N. Imyanitov, Maria A. Caligo, Ian G. Campbell, Frans B. L. Hogervorst, Edith Olah, Orland Diez, Ignacio Blanco, Joan Brunet, Conxi Lazaro, Miquel Angel Pujana, Anna Jakubowska, Jacek Gronwald, Jan Lubinski, Grzegorz Sukiennicki, Rosa B. Barkardottir, Marie Plante, Jacques Simard, Penny Soucy, Marco Montagna, Silvia Tognazzo, Manuel R. Teixeira, Vernon S. Pankratz, Xianshu Wang, Noralane Lindor, Csilla I. Szabo, Noah Kauff, Joseph Vijai, Carol A. Aghajanian, Georg Pfeiler, Andreas Berger, Christian F. Singer, Muy-Kheng Tea, Catherine M. Phelan, Mark H. Greene, Phuong L. Mai, Gad Rennert, Anna Marie Mulligan, Sandrine Tchatchou, Irene L. Andrulis, Gord Glendon, Amanda Ewart Toland, Uffe Birk Jensen, Torben A. Kruse, Mads Thomassen, Anders Bojesen, Jamal Zidan, Eitan Friedman, Yael Laitman, Maria Soller, Annelie Liljegren, Brita Arver, Zakaria Einbeigi, Marie Stenmark-Askmalm, Olufunmilayo I. Olopade, Robert L. Nussbaum, Timothy R. Rebbeck, Katherine L. Nathanson, Susan M. Domchek, Karen H. Lu, Beth Y. Karlan, Christine Walsh, Jenny Lester, Alexander Hein, Arif B. Ekici, Matthias W. Beckmann, Peter A. Fasching, Diether Lambrechts, Els van Nieuwenhuysen, Ignace Vergote, Sandrina Lambrechts, Ed Dicks, Jennifer A. Doherty, Kristine G. Wicklund, Mary Anne Rossing, Anja Rudolph, Jenny Chang-Claude, Shan Wang-Gohrke, Ursula Eilber, Kirsten B. Moysich, Kunle Odunsi, Lara Sucheston, Shashi Lele, Lynne R. Wilkens, Marc T. Goodman, Pamela J. Thompson, Yurii B. Shvetsov, Ingo B. Runnebaum, Matthias Dürst, Peter Hillemanns, Thilo Dörk, Natalia Antonenkova, Natalia Bogdanova, Arto Leminen, Liisa M. Pelttari, Ralf Butzow, Francesmary Modugno, Joseph L. Kelley, Robert P. Edwards, Roberta B. Ness, Andreas Du Bois, Florian Heitz, Ira Schwaab, Philipp Harter, Keitaro Matsuo, Satoyo Hosono, Sandra Orsulic, Allan Jensen, Susanne Kruger Kjaer, Estrid Hogdall, Hanis Nazihah Hasmad, Mat Adenan Noor Azmi, Soo-Hwang Teo, Yin-Ling Woo, Brooke L. Fridley, Ellen L. Goode, Julie M. Cunningham, Robert A. Vierkant, Fiona Bruinsma, Graham G. Giles, Dong Liang, Michelle A. T. Hildebrandt, Xifeng Wu, Douglas A. Levine, Maria Bisogna, Andrew Berchuck, Edwin S. Iversen, Joellen M. Schildkraut, Patrick Concannon, Rachel Palmieri Weber, Daniel W. Cramer, Kathryn L. Terry, Elizabeth M. Poole, Shelley S. Tworoger, Elisa V. Bandera, Irene Orlow, Sara H. Olson, Camilla Krakstad, Helga B. Salvesen, Ingvild L. Tangen, Line Bjorge, Anne M. van Altena, Katja K. H. Aben, Lambertus A. Kiemeney, Leon F. A. G. Massuger, Melissa Kellar, Angela Brooks-Wilson, Linda E. Kelemen, Linda S. Cook, Nhu D. Le, Cezary Cybulski, Hannah Yang, Jolanta Lissowska, Louise A. Brinton, Nicolas Wentzensen, Claus Hogdall, Lene Lundvall, Lotte Nedergaard, Helen Baker, Honglin Song, Diana Eccles, Ian McNeish, James Paul, Karen Carty, Nadeem Siddiqui, Rosalind Glasspool, Alice S. Whittemore, Joseph H. Rothstein, Valerie McGuire, Weiva Sieh, Bu-Tian Ji, Wei Zheng, Xiao-Ou Shu, Yu-Tang Gao, Barry Rosen, Harvey A. Risch, John R. McLaughlin, Steven A. Narod, Alvaro N. Monteiro, Ann Chen, Hui-Yi Lin, Jenny Permuth-Wey, Thomas A. Sellers, Ya-Yu Tsai, Zhihua Chen, Argyrios Ziogas, Hoda Anton-Culver, Aleksandra Gentry-Maharaj, Usha Menon, Patricia Harrington, Alice W. Lee, Anna H. Wu, Celeste L. Pearce, Gerry Coetzee, Malcolm C. Pike, Agnieszka Dansonka-Mieszkowska, Agnieszka Timorek, Iwona K. Rzepecka, Jolanta Kupryjanczyk, Matt Freedman, Houtan Noushmehr, Douglas F. Easton, Kenneth Offit, Fergus J. Couch, Simon Gayther, Paul P. Pharoah, Antonis C. Antoniou, Georgia Chenevix-Trench

Date Published: 1st Feb 2015

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Weight stigma "gets under the skin"-evidence for an adapted psychological mediation framework: a systematic review.
LIFE Adult

Abstract (Expand)

OBJECTIVE: Research consistently shows a negative view of individuals with obesity in the general public and in various other settings. Stigma and discrimination can be considered chronic stressors, … as these factors have a profound impact on the psychological well-being of the affected individuals. This article proposes a framework that entails a mediation of the adverse effects of discrimination and stigmatization on mental well-being through elevated psychological risk factors that are not unique to weight but that could affect overweight and normal-weight individuals alike. METHODS: A systematic review was conducted to assess the prevalence of psychological risk factors, such as self-esteem and coping, in individuals with obesity. RESULTS: Forty-six articles were assessed and included for detailed analysis. The number of studies on these topics is limited to certain dimensions of psychological processes. The best evaluated association of obesity and psychosocial aspects is seen for self-esteem. Most studies establish a negative association of weight and self-esteem in children and adults. All studies with mediation analysis find a positive mediation through psychological risk factors on mental health outcomes. CONCLUSIONS: This review shows that elevated psychological risk factors are existent in individuals with obesity and that they may be a mediator between weight discrimination and pathopsychological outcomes.

Authors: C. Sikorski, M. Luppa, T. Luck, S. G. Riedel-Heller

Date Published: 29th Jan 2015

Publication Type: Not specified

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers …s of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RESULTS The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. CONCLUSION There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. IMPACT Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

Authors: Paolo Peterlongo, Jenny Chang-Claude, Kirsten B. Moysich, Anja Rudolph, Rita K. Schmutzler, Jacques Simard, Penny Soucy, Rosalind A. Eeles, Douglas F. Easton, Ute Hamann, Stefan Wilkening, Bowang Chen, Matti A. Rookus, Marjanka K. Schmidt, Frederieke H. van der Baan, Amanda B. Spurdle, Logan C. Walker, Felicity Lose, Ana-Teresa Maia, Marco Montagna, Laura Matricardi, Jan Lubinski, Anna Jakubowska, Encarna B. Gómez Garcia, Olufunmilayo I. Olopade, Robert L. Nussbaum, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Banu K. Arun, Beth Y. Karlan, Sandra Orsulic, Jenny Lester, Wendy K. Chung, Alex Miron, Melissa C. Southey, David E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Cecilia M. Dorfling, Elizabeth J. van Rensburg, Yuan Chun Ding, Susan L. Neuhausen, Thomas v. O. Hansen, Anne-Marie Gerdes, Bent Ejlertsen, Lars Jønson, Ana Osorio, Cristina Martínez-Bouzas, Javier Benitez, Edye E. Conway, Kathleen R. Blazer, Jeffrey N. Weitzel, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Giulietta Scuvera, Monica Barile, Filomena Ficarazzi, Frederique Mariette, Stefano Fortuzzi, Alessandra Viel, Giuseppe Giannini, Laura Papi, Aline Martayan, Maria Grazia Tibiletti, Paolo Radice, Athanassios Vratimos, Florentia Fostira, Judy E. Garber, Alan Donaldson, Carole Brewer, Claire Foo, D. Gareth R. Evans, Debra Frost, Diana Eccles, Angela Brady, Jackie Cook, Marc Tischkowitz, Julian Adlard, Julian Barwell, Lisa Walker, Louise Izatt, Lucy E. Side, M. John Kennedy, Mark T. Rogers, Mary E. Porteous, Patrick J. Morrison, Radka Platte, Rosemarie Davidson, Shirley V. Hodgson, Steve Ellis, Trevor Cole, Andrew K. Godwin, Kathleen Claes, Tom van Maerken, Alfons Meindl, Andrea Gehrig, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Hansjoerg Plendl, Karin Kast, Kerstin Rhiem, Nina Ditsch, Norbert Arnold, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Shan Wang-Gohrke, Brigitte Bressac-de Paillerets, Bruno Buecher, Capucine Delnatte, Claude Houdayer, Dominique Stoppa-Lyonnet, Francesca Damiola, Isabelle Coupier, Laure Barjhoux, Laurence Venat-Bouvet, Lisa Golmard, Nadia Boutry-Kryza, Olga M. Sinilnikova, Olivier Caron, Pascal Pujol, Sylvie Mazoyer, Muriel Belotti, Marion Piedmonte, Michael L. Friedlander, Gustavo C. Rodriguez, Larry J. Copeland, Miguel de La Hoya, Pedro Perez Segura, Heli Nevanlinna, Kristiina Aittomäki, Theo A. M. van Os, Hanne E. J. Meijers-Heijboer, Annemarie H. van der Hout, Maaike P. G. Vreeswijk, Nicoline Hoogerbrugge, Margreet G. E. M. Ausems, Helena C. van Doorn, J. Margriet Collée, Edith Olah, Orland Diez, Ignacio Blanco, Conxi Lazaro, Joan Brunet, Lidia Feliubadalo, Cezary Cybulski, Jacek Gronwald, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Grzegorz Sukiennicki, Adalgeir Arason, Jocelyne Chiquette, Manuel R. Teixeira, Curtis Olswold, Fergus J. Couch, Noralane M. Lindor, Xianshu Wang, Csilla I. Szabo, Kenneth Offit, Marina Corines, Lauren Jacobs, Mark E. Robson, Liying Zhang, Vijai Joseph, Andreas Berger, Christian F. Singer, Christine Rappaport, Daphne Geschwantler Kaulich, Georg Pfeiler, Muy-Kheng M. Tea, Catherine M. Phelan, Mark H. Greene, Phuong L. Mai, Gad Rennert, Anna Marie Mulligan, Gord Glendon, Sandrine Tchatchou, Irene L. Andrulis, Amanda Ewart Toland, Anders Bojesen, Inge Sokilde Pedersen, Mads Thomassen, Uffe Birk Jensen, Yael Laitman, Johanna Rantala, Anna von Wachenfeldt, Hans Ehrencrona, Marie Stenmark Askmalm, Åke Borg, Karoline B. Kuchenbaecker, Lesley McGuffog, Daniel Barrowdale, Sue Healey, Andrew Lee, Paul D. P. Pharoah, Georgia Chenevix-Trench, Antonis C. Antoniou, Eitan Friedman

Date Published: 13th Jan 2015

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

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