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1. Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Author

Amare, Azmeraw, Thalamuthu, Anbupalam, Schubert, Klaus, Fullerton, Janice, Ahmed, Muktar, Hartmann, Simon, Papiol, Sergi, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hou, Liping, Hsu, Yi-Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Hasler, Roland, Richard-Lepouriel, Hélène, Perroud, Nader, Backlund, Lena, Bhattacharjee, Abesh, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna, Birner, Armin, Marie-Claire, Cynthia, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Del Zompo, Maria, DePaulo, J, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas, Frisen, Louise, Frye, Mark, Gard, Sébastien, Garnham, Julie, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Fallgatter, Andreas, Stegmaier, Sophia, Ethofer, Thomas, Biere, Silvia, Petrova, Kristiyana, Schuster, Ceylan, Adorjan, Kristina, Budde, Monika, Heilbronner, Maria, Kalman, Janos, Kohshour, Mojtaba, Reich-Erkelenz, Daniela, Schaupp, Sabrina, Schulte, Eva, Senner, Fanny, Vogl, Thomas, Anghelescu, Ion-George, Arolt, Volker, Dannlowski, Udo, Dietrich, Detlef, Figge, Christian, Jäger, Markus, Lang, Fabian, Juckel, Georg, Konrad, Carsten, Reimer, Jens, Schmauß, Max, Schmitt, Andrea, Spitzer, Carsten, von Hagen, Martin, Wiltfang, Jens, Zimmermann, Jörg, Andlauer, Till, Fischer, Andre, Bermpohl, Felix, Ritter, Philipp, Matura, Silke, Gryaznova, Anna, Falkenberg, Irina, Yildiz, Cüneyt, Kircher, Tilo, Schmidt, Julia, Koch, Marius, Gade, Kathrin, Trost, Sarah, Haussleiter, Ida, Lambert, Martin, Rohenkohl, Anja, Kraft, Vivien, Grof, Paul, and Hashimoto, Ryota

Subjects
Bipolar Disorder, Humans, Female, Male, Multifactorial Inheritance, Adult, Middle Aged, Lithium, Treatment Outcome, Bayes Theorem, Genome-Wide Association Study, Glutamic Acid, Cohort Studies, Lithium Compounds, Acetylcholine, Polymorphism, Single Nucleotide, Antimanic Agents
Abstract

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithiums possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P

Published
2023

2. Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis

Author

Merritt, Kate, McCutcheon, Robert A., Aleman, André, Ashley, Sarah, Beck, Katherine, Block, Wolfgang, Bloemen, Oswald J. N., Borgan, Faith, Boules, Christiana, Bustillo, Juan R., Capizzano, Aristides A., Coughlin, Jennifer M., David, Anthony, de la Fuente-Sandoval, Camilo, Demjaha, Arsime, Dempster, Kara, Do, Kim Q., Du, Fei, Falkai, Peter, Galińska-Skok, Beata, Gallinat, Jürgen, Gasparovic, Charles, Ginestet, Cedric E., Goto, Naoki, Graff-Guerrero, Ariel, Ho, Beng-Choon, Howes, Oliver, Jauhar, Sameer, Jeon, Peter, Kato, Tadafumi, Kaufmann, Charles A., Kegeles, Lawrence S., Keshavan, Matcheri S., Kim, Sang-Young, King, Bridget, Kunugi, Hiroshi, Lauriello, J., León-Ortiz, Pablo, Liemburg, Edith, Mcilwain, Meghan E., Modinos, Gemma, Mouchlianitis, Elias, Nakamura, Jun, Nenadic, Igor, Öngür, Dost, Ota, Miho, Palaniyappan, Lena, Pantelis, Christos, Patel, Tulsi, Plitman, Eric, Posporelis, Sotirios, Purdon, Scot E., Reichenbach, Jürgen R., Renshaw, Perry F., Reyes-Madrigal, Francisco, Russell, Bruce R., Sawa, Akira, Schaefer, Martin, Shungu, Dikoma C., Smesny, Stefan, Stanley, Jeffrey A., Stone, James, Szulc, Agata, Taylor, Reggie, Thakkar, Katharine N., Théberge, Jean, Tibbo, Philip G., van Amelsvoort, Thérèse, Walecki, Jerzy, Williamson, Peter C., Wood, Stephen J., Xin, Lijing, Yamasue, Hidenori, McGuire, Philip, and Egerton, Alice

Published
2023
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3. The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease

Author

Franzmeier, Nicolai, Ren, Jinyi, Damm, Alexander, Monté-Rubio, Gemma, Boada, Mercè, Ruiz, Agustín, Ramirez, Alfredo, Jessen, Frank, Düzel, Emrah, Rodríguez Gómez, Octavio, Benzinger, Tammie, Goate, Alison, Karch, Celeste M., Fagan, Anne M., McDade, Eric, Buerger, Katharina, Levin, Johannes, Duering, Marco, Dichgans, Martin, Suárez-Calvet, Marc, Haass, Christian, Gordon, Brian A., Lim, Yen Ying, Masters, Colin L., Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael, Milz, Esther, Moreno-Grau, Sonia, Teipel, Stefan, Grothe, Michel J, Kilimann, Ingo, Rossor, Martin, Fox, Nick, Laske, Christoph, Chhatwal, Jasmeer, Falkai, Peter, Perneczky, Robert, Lee, Jae-Hong, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Nestor, Peter, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef, Spruth, Eike J., Franke, Christiana, Schneider, Anja, Westerteicher, Christine, Speck, Oliver, Wiltfang, Jens, Bartels, Claudia, Araque Caballero, Miguel Ángel, Metzger, Coraline, Bittner, Daniel, Salloway, Stephen, Danek, Adrian, Hassenstab, Jason, Yakushev, Igor, Schofield, Peter R., Morris, John C., Bateman, Randall J., and Ewers, Michael

Published
2021
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4. Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia

Author

Hasan, A, Wobrock, T, Guse, B, Langguth, B, Landgrebe, M, Eichhammer, P, Frank, E, Cordes, J, Wölwer, W, Musso, F, Winterer, G, Gaebel, W, Hajak, G, Ohmann, C, Verde, P E, Rietschel, M, Ahmed, R, Honer, W G, Dechent, P, Malchow, B, Castro, M F U, Dwyer, D, Cabral, C, Kreuzer, P M, Poeppl, T B, Schneider-Axmann, T, Falkai, P, and Koutsouleris, N

Published
2017
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6. Genome-wide association study of obsessive-compulsive disorder

Author

Stewart, S E, Yu, D, Scharf, J M, Neale, B M, Fagerness, J A, Mathews, C A, Arnold, P D, Evans, P D, Gamazon, E R, Osiecki, L, McGrath, L, Haddad, S, Crane, J, Hezel, D, Illman, C, Mayerfeld, C, Konkashbaev, A, Liu, C, Pluzhnikov, A, Tikhomirov, A, Edlund, C K, Rauch, S L, Moessner, R, Falkai, P, Maier, W, Ruhrmann, S, Grabe, H-J, Lennertz, L, Wagner, M, Bellodi, L, Cavallini, M C, Richter, M A, Cook, Jr, E H, Kennedy, J L, Rosenberg, D, Stein, D J, Hemmings, S M J, Lochner, C, Azzam, A, Chavira, D A, Fournier, E, Garrido, H, Sheppard, B, Umaña, P, Murphy, D L, Wendland, J R, Veenstra-VanderWeele, J, Denys, D, Blom, R, Deforce, D, Van Nieuwerburgh, F, Westenberg, H G M, Walitza, S, Egberts, K, Renner, T, Miguel, E C, Cappi, C, Hounie, A G, Conceição do Rosário, M, Sampaio, A S, Vallada, H, Nicolini, H, Lanzagorta, N, Camarena, B, Delorme, R, Leboyer, M, Pato, C N, Pato, M T, Voyiaziakis, E, Heutink, P, Cath, D C, Posthuma, D, Smit, J H, Samuels, J, Bienvenu, O J, Cullen, B, Fyer, A J, Grados, M A, Greenberg, B D, McCracken, J T, Riddle, M A, Wang, Y, Coric, V, Leckman, J F, Bloch, M, Pittenger, C, Eapen, V, Black, D W, Ophoff, R A, Strengman, E, Cusi, D, Turiel, M, Frau, F, Macciardi, F, Gibbs, J R, Cookson, M R, Singleton, A, Hardy, J, Crenshaw, A T, Parkin, M A, Mirel, D B, Conti, D V, Purcell, S, Nestadt, G, Hanna, G L, Jenike, M A, Knowles, J A, Cox, N, and Pauls, D L

Published
2013
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10. Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis

Author

nternational Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC), OCD Collaborative Genetics Association Studies (OCGAS): Arnold PD, Askland KD, Barlassina C, Bellodi L, Bienvenu OJ, Black D, Bloch M, Brentani H, Burton CL, Camarena B, Cappi C, Cath D, Cavallini M, Conti D, Cook E, Coric V, Cullen BA, Cusi D, Davis LK, Delorme R, Denys D, Derks E, Eapen V, Edlund C, Erdman L, Falkai P, Figee M, Fyer AJ, Geller DA, Goes FS, Grabe H, Grados MA, Greenberg BD, Grünblatt E, Guo W, Hanna GL, Hemmings S, Hounie AG, Jenicke M, Keenan C, Kennedy J, Khramtsova EA, Konkashbaev A, Knowles JA, Krasnow J, Lange C, Lanzagorta N, Leboyer M, Lennertz L, Li B, Liang KY, Lochner C, Macciardi F, Maher B, Maier W, Marconi M, Mathews CA, Matthesien M, McCracken JT, McLaughlin NC, Miguel EC, Moessner R, Murphy DL, Neale B, Nestadt G, Nestadt P, Nicolini H, Nurmi E, Osiecki L, Pauls DL, Piacentini J, Posthuma D, Pulver AE, Qin HD, Rasmussen SA, Rauch S, Richter MA, Riddle MA, Ripke S, Ruhrmann S, Sampaio AS, Samuels JF, Scharf JM, Shugart YY, Smit J, Stein D, Stewart SE, Turiel M, Vallada H, Veenstra-VanderWeele J, Wagner M, Walitza S, Wang Y, Wendland J, Vulink N, Yu D, Zai G., Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Reproduction & Development (AR&D), Human genetics, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, APH - Mental Health, Arnold, Paul D, Askland, Kathleen D, Barlassina, Cristina, Bellodi, Laura, Bienvenu, O. J, Black, Donald, Bloch, Michael, Brentani, Helena, Burton, Christie L, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Conti, David, Cook, Edwin, Coric, Vladimir, Cullen, Bernadette A, Cusi, Danielle, Davis, Lea K, Delorme, Richard, Denys, Damiaan, Derks, Eske, Eapen, Valsamma, Edlund, Christopher, Erdman, Lauren, Falkai, Peter, Figee, Martijn, Fyer, Abigail J, Geller, Daniel A, Goes, Fernando S, Grabe, Han, Grados, Marcos A, Greenberg, Benjamin D, Grünblatt, Edna, Guo, Wei, Hanna, Gregory L, Hemmings, Sian, Hounie, Ana G, Jenicke, Michael, Keenan, Clare, Kennedy, Jame, Khramtsova, Ekaterina A, Konkashbaev, Anuar, Knowles, James A, Krasnow, Janice, Lange, Cristophe, Lanzagorta, Nuria, Leboyer, Marion, Lennertz, Leonhard, Li, Bingbin, Liang, K. y, Lochner, Christine, Macciardi, Fabio, Maher, Brion, Maier, Wolfgang, Marconi, Maurizio, Mathews, Carol A, Matthesien, Manuel, Mccracken, James T, Mclaughlin, Nicole C, Miguel, Euripedes C, Moessner, Rainald, Murphy, Dennis L, Neale, Benjamin, Nestadt, Gerald, Nestadt, Paul, Nicolini, Humberto, Nurmi, Ericka, Osiecki, Lisa, Pauls, David L, Piacentini, John, Posthuma, Danielle, Pulver, Ann E, Qin, H. d, Rasmussen, Steven A, Rauch, Scott, Richter, Margaret A, Riddle, Mark A, Ripke, Stephan, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack F, Scharf, Jeremiah M, Shugart, Yin Yao, Smit, Jan, Stein, Daniel, Stewart, S. Evelyn, Turiel, Maurizio, Vallada, Homero, Veenstra vanderweele, Jeremy, Wagner, Michael, Walitza, Susanne, Wang, Y, Wendland, Jen, Vulink, Nienke, Yu, Dongmei, Zai, Gwyneth, and Netherlands Institute for Neuroscience (NIN)

Subjects
0301 basic medicine, Genetics, TRANSTORNO OBSESSIVO-COMPULSIVO, Single-nucleotide polymorphism, Odds ratio, Biology, Heritability, Confidence interval, Genetic architecture, Minor allele frequency, 03 medical and health sciences, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, Journal Article, SNP, SDG 2 - Zero Hunger, Molecular Biology, 030217 neurology & neurosurgery, Genetic association
Abstract

Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10(-7); odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10(-6); OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10(-6); OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.154.

Published
2018

17. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Author

Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi-Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andreas, Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, Witt, Stephanie H., Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, Rietschel, Marcella, McMahon, Francis J., Schulze, Thomas G., and Baune, Bernhard T.

Abstract

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS pvalue thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Aldascale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various pvalue thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Published
2021
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18. Erratum: Genome-wide association study of obsessive-compulsive disorder

Author

Stewart, S E, Yu, D, Scharf, J M, Neale, B M, Fagerness, J A, Mathews, C A, Arnold, P D, Evans, P D, Gamazon, E R, Osiecki, L, McGrath, L, Haddad, S, Crane, J, Hezel, D, Illman, C, Mayerfeld, C, Konkashbaev, A, Liu, C, Pluzhnikov, A, Tikhomirov, A, Edlund, C K, Rauch, S L, Moessner, R, Falkai, P, Maier, W, Ruhrmann, S, Grabe, H-J, Lennertz, L, Wagner, M, Bellodi, L, Cavallini, M C, Richter, M A, Cook, Jr, E H, Kennedy, J L, Rosenberg, D, Stein, D J, Hemmings, S M J, Lochner, C, Azzam, A, Chavira, D A, Fournier, E, Garrido, H, Sheppard, B, Umaña, P, Murphy, D L, Wendland, J R, Veenstra-Vander Weele, J, Denys, D, Blom, R, Deforce, D, Van Nieuwerburgh, F, Westenberg, H G M, Walitza, S, Egberts, K, Renner, T, Miguel, E C, Cappi, C, Hounie, A G, Conceição do Rosário, M, Sampaio, A S, Vallada, H, Nicolini, H, Lanzagorta, N, Camarena, B, Delorme, R, Leboyer, M, Pato, C N, Pato, M T, Voyiaziakis, E, Heutink, P, Cath, D C, Posthuma, D, Smit, J H, Samuels, J, Bienvenu, O J, Cullen, B, Fyer, A J, Grados, M A, Greenberg, B D, McCracken, J T, Riddle, M A, Wang, Y, Coric, V, Leckman, J F, Bloch, M, Pittenger, C, Eapen, V, Black, D W, Ophoff, R A, Strengman, E, Cusi, D, Turiel, M, Frau, F, Macciardi, F, Gibbs, J R, Cookson, M R, Singleton, A, Hardy, J, Crenshaw, A T, Parkin, M A, Mirel, D B, Conti, D V, Purcell, S, Nestadt, G, Hanna, G L, Jenike, M A, Knowles, J A, Cox, N, and Pauls, D L

Published
2013
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19. The BDNFVal66MetSNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease

Author

Franzmeier, Nicolai, Ren, Jinyi, Damm, Alexander, Monté-Rubio, Gemma, Boada, Mercè, Ruiz, Agustín, Ramirez, Alfredo, Jessen, Frank, Düzel, Emrah, Rodríguez Gómez, Octavio, Benzinger, Tammie, Goate, Alison, Karch, Celeste M., Fagan, Anne M., McDade, Eric, Buerger, Katharina, Levin, Johannes, Duering, Marco, Dichgans, Martin, Suárez-Calvet, Marc, Haass, Christian, Gordon, Brian A., Lim, Yen Ying, Masters, Colin L., Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael, Milz, Esther, Moreno-Grau, Sonia, Teipel, Stefan, Grothe, Michel J, Kilimann, Ingo, Rossor, Martin, Fox, Nick, Laske, Christoph, Chhatwal, Jasmeer, Falkai, Peter, Perneczky, Robert, Lee, Jae-Hong, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Nestor, Peter, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef, Spruth, Eike J., Franke, Christiana, Schneider, Anja, Westerteicher, Christine, Speck, Oliver, Wiltfang, Jens, Bartels, Claudia, Araque Caballero, Miguel Ángel, Metzger, Coraline, Bittner, Daniel, Salloway, Stephen, Danek, Adrian, Hassenstab, Jason, Yakushev, Igor, Schofield, Peter R., Morris, John C., Bateman, Randall J., and Ewers, Michael

Abstract

In Alzheimer’s disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNFVal66Met) is associated with worse impact of primary AD pathology (beta-amyloid, Aß) on neurodegeneration and cognitive decline, rendering BDNFVal66Metan important modulating factor of cognitive impairment in AD. However, the effect of BDNFVal66Meton functional networks that may underlie cognitive impairment in AD is poorly understood. Using a cross-validation approach, we first explored in subjects with autosomal dominant AD (ADAD) from the Dominantly Inherited Alzheimer Network (DIAN) the effect of BDNFVal66Meton resting-state fMRI assessed functional networks. In seed-based connectivity analysis of six major large-scale networks, we found a stronger decrease of hippocampus (seed) to medial-frontal connectivity in the BDNFVal66Metcarriers compared to BDNFValhomozogytes. BDNFVal66Metwas not associated with connectivity in any other networks. Next, we tested whether the finding of more pronounced decrease in hippocampal-medial-frontal connectivity in BDNFVal66Metcould be also found in elderly subjects with sporadically occurring Aß, including a group with subjective cognitive decline (N?=?149, FACEHBI study) and a group ranging from preclinical to AD dementia (N?=?114, DELCODE study). In both of these independently recruited groups, BDNFVal66Metwas associated with a stronger effect of more abnormal Aß-levels (assessed by biofluid-assay or amyloid-PET) on hippocampal-medial-frontal connectivity decreases, controlled for hippocampus volume and other confounds. Lower hippocampal-medial-frontal connectivity was associated with lower global cognitive performance in the DIAN and DELCODE studies. Together these results suggest that BDNFVal66Metis selectively associated with a higher vulnerability of hippocampus-frontal connectivity to primary AD pathology, resulting in greater AD-related cognitive impairment.

Published
2021
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20. Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia

Author

Hasan, A, primary, Wobrock, T, additional, Guse, B, additional, Langguth, B, additional, Landgrebe, M, additional, Eichhammer, P, additional, Frank, E, additional, Cordes, J, additional, Wölwer, W, additional, Musso, F, additional, Winterer, G, additional, Gaebel, W, additional, Hajak, G, additional, Ohmann, C, additional, Verde, P E, additional, Rietschel, M, additional, Ahmed, R, additional, Honer, W G, additional, Dechent, P, additional, Malchow, B, additional, Castro, M F U, additional, Dwyer, D, additional, Cabral, C, additional, Kreuzer, P M, additional, Poeppl, T B, additional, Schneider-Axmann, T, additional, Falkai, P, additional, and Koutsouleris, N, additional

Published
2016
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21. EPO treatment preserves gray matter in discrete brain regions of chronic schizophrenic patients: indication of areas with most progressive neurodegeneration inherent to the disease process

Author

Wüstenberg, T, primary, Begemann, M, additional, Bartels, C, additional, Gefeller, O, additional, Stawicki, S, additional, Hinze-Selch, D, additional, Mohr, A, additional, Falkai, P, additional, Aldenhoff, J B, additional, Knauth, M, additional, Nave, K-A, additional, and Ehrenreich, H, additional

Published
2010
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23. Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

Author

Ehrenreich, H, primary, Hinze-Selch, D, additional, Stawicki, S, additional, Aust, C, additional, Knolle-Veentjer, S, additional, Wilms, S, additional, Heinz, G, additional, Erdag, S, additional, Jahn, H, additional, Degner, D, additional, Ritzen, M, additional, Mohr, A, additional, Wagner, M, additional, Schneider, U, additional, Bohn, M, additional, Huber, M, additional, Czernik, A, additional, Pollmächer, T, additional, Maier, W, additional, Sirén, A-L, additional, Klosterkötter, J, additional, Falkai, P, additional, Rüther, E, additional, Aldenhoff, J B, additional, and Krampe, H, additional

Published
2006
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24. Erythropoietin: a candidate compound for neuroprotection in schizophrenia

Author

Ehrenreich, H, primary, Degner, D, additional, Meller, J, additional, Brines, M, additional, Béhé, M, additional, Hasselblatt, M, additional, Woldt, H, additional, Falkai, P, additional, Knerlich, F, additional, Jacob, S, additional, von Ahsen, N, additional, Maier, W, additional, Brück, W, additional, Rüther, E, additional, Cerami, A, additional, Becker, W, additional, and Sirén, A-L, additional

Published
2003
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