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1. Exploring the genetics of lithium response in bipolar disorders

Author

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

Published
2024
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2. Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

Author

Ou, Anna H., Rosenthal, Sara B., Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Alda, Martin, Amare, Azmeraw T., Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bauer, Michael, Baune, Bernhard T., Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M., Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R., Colom, Francesc, Cousins, David A., Cruceanu, Cristiana, Czerski, Piotr M., Dantas, Clarissa R., Dayer, Alexandre, Del Zompo, Maria, Degenhardt, Franziska, DePaulo, J. Raymond, Étain, Bruno, Falkai, Peter, Fellendorf, Frederike Tabea, Ferensztajn-Rochowiak, Ewa, Forstner, Andreas J., Frisén, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kato, Tadafumi, Kittel-Schneider, Sarah, König, Barbara, Kuo, Po-Hsiu, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Jaramillo, Carlos A. López, MacQueen, Glenda, Maj, Mario, Manchia, Mirko, Marie-Claire, Cynthia, Martinsson, Lina, Mattheisen, Manuel, McCarthy, Michael J., McElroy, Susan L., McMahon, Francis J., Mitchell, Philip B., Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, Ösby, Urban, Ozaki, Norio, Papiol, Sergi, Perlis, Roy H., Pisanu, Claudia, Potash, James B., Pfennig, Andrea, Reich-Erkelenz, Daniela, Reif, Andreas, Reininghaus, Eva Z., Rietschel, Marcella, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schubert, K. Oliver, Schulze, Thomas G., Schweizer, Barbara W., Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie, Wray, Naomi R., Wright, Adam, Young, L. Trevor, Zandi, Peter P., and Kelsoe, John R.

Published
2024
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3. Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder

Author

Amare, Azmeraw T., Thalamuthu, Anbupalam, Schubert, Klaus Oliver, Fullerton, Janice M., 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 Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Marie-Claire, Cynthia, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Fallgatter, Andreas J., Stegmaier, Sophia, Ethofer, Thomas, Biere, Silvia, Petrova, Kristiyana, Schuster, Ceylan, Adorjan, Kristina, Budde, Monika, Heilbronner, Maria, Kalman, Janos L., Kohshour, Mojtaba Oraki, Reich-Erkelenz, Daniela, Schaupp, Sabrina K., Schulte, Eva C., Senner, Fanny, Vogl, Thomas, Anghelescu, Ion-George, Arolt, Volker, Dannlowski, Udo, Dietrich, Detlef, Figge, Christian, Jäger, Markus, Lang, Fabian U., Juckel, Georg, Konrad, Carsten, Reimer, Jens, Schmauß, Max, Schmitt, Andrea, Spitzer, Carsten, von Hagen, Martin, Wiltfang, Jens, Zimmermann, Jörg, Andlauer, Till F. M., 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 S., Lambert, Martin, Rohenkohl, Anja C., Kraft, Vivien, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Ferensztajn-Rochowiak, Ewa, 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, Colom, Francesc, Millischer, Vincent, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Pfennig, Andrea, Pisanu, Claudia, 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., Clark, Scott R., and Baune, Bernhard T.

Published
2023
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4. Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder

Author

Bauer, Michael, Glenn, Tasha, Achtyes, Eric D., Alda, Martin, Agaoglu, Esen, Altınbaş, Kürsat, Andreassen, Ole A., Angelopoulos, Elias, Ardau, Raffaella, Aydin, Memduha, Ayhan, Yavuz, Baethge, Christopher, Bauer, Rita, Baune, Bernhard T., Balaban, Ceylan, Becerra-Palars, Claudia, Behere, Aniruddh P., Behere, Prakash B., Belete, Habte, Belete, Tilahun, Belizario, Gabriel Okawa, Bellivier, Frank, Belmaker, Robert H., Benedetti, Francesco, Berk, Michael, Bersudsky, Yuly, Bicakci, Şule, Birabwa-Oketcho, Harriet, Bjella, Thomas D., Brady, Conan, Cabrera, Jorge, Cappucciati, Marco, Castro, Angela Marianne Paredes, Chen, Wei-Ling, Cheung, Eric Y. W., Chiesa, Silvia, Crowe, Marie, Cuomo, Alessandro, Dallaspezia, Sara, Del Zompo, Maria, Desai, Pratikkumar, Dodd, Seetal, Etain, Bruno, Fagiolini, Andrea, Fellendorf, Frederike T., Ferensztajn-Rochowiak, Ewa, Fiedorowicz, Jess G., Fountoulakis, Kostas N., Frye, Mark A., Geoffroy, Pierre A., Gitlin, Michael J., Gonzalez-Pinto, Ana, Gottlieb, John F., Grof, Paul, Haarman, Bartholomeus C. M., Harima, Hirohiko, Hasse-Sousa, Mathias, Henry, Chantal, Hoffding, Lone, Houenou, Josselin, Imbesi, Massimiliano, Isometsä, Erkki T., Ivkovic, Maja, Janno, Sven, Johnsen, Simon, Kapczinski, Flávio, Karakatsoulis, Gregory N., Kardell, Mathias, Kessing, Lars Vedel, Kim, Seong Jae, König, Barbara, Kot, Timur L., Koval, Michael, Kunz, Mauricio, Lafer, Beny, Landén, Mikael, Larsen, Erik R., Lenger, Melanie, Licht, Rasmus W., Lopez-Jaramillo, Carlos, MacKenzie, Alan, Madsen, Helle Østergaard, Madsen, Simone Alberte Kongstad A., Mahadevan, Jayant, Mahardika, Agustine, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Monica, Martini, Julia, Martiny, Klaus, Mashima, Yuki, McLoughlin, Declan M., Meesters, Ybe, Melle, Ingrid, Meza-Urzúa, Fátima, Mikolas, Pavol, Mok, Yee Ming, Monteith, Scott, Moorthy, Muthukumaran, Morken, Gunnar, Mosca, Enrica, Mozzhegorov, Anton A., Munoz, Rodrigo, Mythri, Starlin V., Nacef, Fethi, Nadella, Ravi K., Nakanotani, Takako, Nielsen, René Ernst, O’Donovan, Claire, Omrani, Adel, Osher, Yamima, Ouali, Uta, Pantovic-Stefanovic, Maja, Pariwatcharakul, Pornjira, Petite, Joanne, Petzold, Johannes, Pfennig, Andrea, Ruiz, Yolanda Pica, Pinna, Marco, Pompili, Maurizio, Porter, Richard J., Quiroz, Danilo, Rabelo-da-Ponte, Francisco Diego, Ramesar, Raj, Rasgon, Natalie, Ratta-apha, Woraphat, Ratzenhofer, Michaela, Redahan, Maria, Reddy, M. S., Reif, Andreas, Reininghaus, Eva Z., Richards, Jenny Gringer, Ritter, Philipp, Rybakowski, Janusz K., Sathyaputri, Leela, Scippa, Angela M., Simhandl, Christian, Smith, Daniel, Smith, José, Stackhouse, Jr, Paul W., Stein, Dan J., Stilwell, Kellen, Strejilevich, Sergio, Su, Kuan-Pin, Subramaniam, Mythily, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Tanra, Andi J., Tatebayashi, Yoshitaka, Teh, Wen Lin, Tondo, Leonardo, Torrent, Carla, Tuinstra, Daniel, Uchida, Takahito, Vaaler, Arne E., Vieta, Eduard, Viswanath, Biju, Yoldi-Negrete, Maria, Yalcinkaya, Oguz Kaan, Young, Allan H., Zgueb, Yosra, and Whybrow, Peter C.

Published
2023
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5. Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Author

Coombes, Brandon J, Millischer, Vincent, Batzler, Anthony, Larrabee, Beth, Hou, Liping, Papiol, Sergi, Heilbronner, Urs, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Amare, Azmeraw T, Ardau, Raffaella, Arias, Barbara, Aubry, Jean-Michel, Backlund, Lena, Bauer, Michael, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Étain, Bruno, Falkai, Peter, Ferensztajn-Rochowiak, Ewa, Forstner, Andreas J, Frisen, Louise, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kato, Tadafumi, Kelsoe, John R, Kittel-Schneider, Sarah, König, Barbara, Kuo, Po-Hsiu, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J, McElroy, Susan L, Mitchell, Philip B, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Tomas, O'Donovan, Claire, Osby, Urban, Ozaki, Norio, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Reif, Andreas, Reininghaus, Eva, Rietschel, Marcella, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Schofield, Peter R, Schubert, Klaus Oliver, Schweizer, Barbara W, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tortorella, Alfonso, and Turecki, Gustavo

Subjects
Brain Disorders, Serious Mental Illness, Prevention, Attention Deficit Hyperactivity Disorder (ADHD), Schizophrenia, Depression, Mental Health, Bipolar Disorder, Behavioral and Social Science, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Adherence, Attention-deficit/hyperactivity disorder, Bipolar disorder, Lithium response, Polygenic risk scores
Abstract

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.

Published
2021

6. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author

Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Amare, Azmeraw T, Frank, Joseph, Streit, Fabian, Adl, 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, Marie-Claire, Cynthia, Cearns, Micah, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Étain, Bruno, 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, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Ferensztajn-Rochowiak, Ewa, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J, McElroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Reif, Andreas, Reininghaus, Eva, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Schofield, Peter R, Schweizer, Barbara W, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M, Squassina, Alessio, and Stamm, Thomas

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Mental Health, Brain Disorders, Schizophrenia, Bipolar Disorder, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Depression, Depressive Disorder, Major, Genetic Predisposition to Disease, Humans, Lithium, Multifactorial Inheritance, Risk Factors, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Clinical Sciences, Public Health and Health Services, Clinical sciences, Neurosciences, Biological psychology
Abstract

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

Published
2021

11. Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder

Author

Reinbold, Céline S, Forstner, Andreas J, Hecker, Julian, Fullerton, Janice M, Hoffmann, Per, Hou, Liping, Heilbronner, Urs, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Benabarre, Antonio, Bengesser, Susanne, Bhattacharjee, Abesh K, Biernacka, Joanna M, Birner, Armin, Marie-Claire, Cynthia, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Clark, Scott R, Colom, Francesc, Cousins, David A, Cruceanu, Cristiana, Czerski, Piotr M, Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Frisén, Louise, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Jamain, Stéphane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Jaramillo, Carlos A López, MacQueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, McCarthy, Michael J, McElroy, Susan L, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Ösby, Urban, Ozaki, Norio, Perlis, Roy H, Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A, Schofield, Peter R, Schubert, K Oliver, Schweizer, Barbara W, Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M, Smoller, Jordan W, Squassina, Alessio, Stamm, Thomas J, Stopkova, Pavla, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie H, Wright, Adam J, Young, L Trevor, Zandi, Peter P, Potash, James B, DePaulo, J Raymond, Bauer, Michael, Reininghaus, Eva, Novák, Tomáš, and Aubry, Jean-Michel

Subjects
Mental Health, Brain Disorders, Clinical Research, Serious Mental Illness, Bipolar Disorder, Human Genome, Genetics, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Mental health, bipolar disorder, lithium response, microRNA, common variants, genome-wide association study, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.

Published
2018

12. Correction: Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author

Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Amare, Azmeraw T., Frank, Joseph, Streit, Fabian, Adl, 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, Marie-Claire, Cynthia, Cearns, Micah, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R., Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, 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, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Ferensztajn-Rochowiak, Ewa, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Maj, Mario, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James B., Reif, Andreas, Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tekola-Ayele, Fasil, Tortorella, Alfonso, Turecki, Gustavo, Veeh, Julia, Vieta, Eduard, Witt, Stephanie H., Roberts, Gloria, Zandi, Peter P., Alda, Martin, Bauer, Michael, McMahon, Francis J., Mitchell, Philip B., Schulze, Thomas G., Rietschel, Marcella, and Baune, Bernhard T.

Published
2022
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16. Expressive Quantale-Valued Logics for Coalgebras: An Adjunction-Based Approach

Author

Harsh Beohar and Sebastian Gurke and Barbara König and Karla Messing and Jonas Forster and Lutz Schröder and Paul Wild, Beohar, Harsh, Gurke, Sebastian, König, Barbara, Messing, Karla, Forster, Jonas, Schröder, Lutz, Wild, Paul, Harsh Beohar and Sebastian Gurke and Barbara König and Karla Messing and Jonas Forster and Lutz Schröder and Paul Wild, Beohar, Harsh, Gurke, Sebastian, König, Barbara, Messing, Karla, Forster, Jonas, Schröder, Lutz, and Wild, Paul

Abstract

We address the task of deriving fixpoint equations from modal logics characterizing behavioural equivalences and metrics (summarized under the term conformances). We rely on an earlier work that obtains Hennessy-Milner theorems as corollaries to a fixpoint preservation property along Galois connections between suitable lattices. We instantiate this to the setting of coalgebras, in which we spell out the compatibility property ensuring that we can derive a behaviour function whose greatest fixpoint coincides with the logical conformance. We then concentrate on the linear-time case, for which we study coalgebras based on the machine functor living in Eilenberg-Moore categories, a scenario for which we obtain a particularly simple logic and fixpoint equation. The theory is instantiated to concrete examples, both in the branching-time case (bisimilarity and behavioural metrics) and in the linear-time case (trace equivalences and trace distances).

Published
2024
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17. Approximating Fixpoints of Approximated Functions (Invited Talk)

Author

Barbara König, König, Barbara, Barbara König, and König, Barbara

Abstract

There is a large body of work on fixpoint theorems, guaranteeing the existence of fixpoints for certain functions and providing methods for computing them. This includes for instance Banachs’s fixpoint theorem, the well-known result by Knaster-Tarski that is frequently employed in computer science and Kleene iteration. It is less clear how to compute fixpoints if the function whose (least) fixpoint we are interested in is not known exactly, but can only be obtained by a sequence of subsequently better approximations. This scenario occurs for instance in the context of reinforcement learning, where the probabilities of a Markov decision process (MDP) - for which one wants to learn a strategy - are unknown and can only be sampled. There are several solutions to this problem where the fixpoint computation (for determining the value vector and the optimal strategy) and the exploration of the model are interleaved. However, these methods work only well for discounted MDPs, that is in the contractive setting, but not for general MDPs, that is for non-expansive functions. After describing and motivating the problem, we will in particular concentrate on the non-expansive case. There are many interesting systems who value vectors can be obtained by determining the fixpoints of non-expansive functions. Other than contractive functions, they do not guarantee uniqueness of the fixpoint, making it more difficult to approximate the least fixpoint by methods other than Kleene iteration. And also Kleene iteration fails if the function under consideration is only approximated. We hence describe a dampened Mann iteration scheme for (higher-dimensional) functions on the reals that converges to the least fixpoint from everywhere. This scheme can also be adapted to functions that are approximated, under certain conditions. We will in particular study the case of MDPs and consider a related problem that arises when performing model-checking for quantitative mu-calculi, which involves the

Published
2024
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18. Behavioural Metrics: Compositionality of the Kantorovich Lifting and an Application to Up-To Techniques

Author

D'Angelo, Keri, Gurke, Sebastian, Kirss, Johanna Maria, König, Barbara, Najafi, Matina, Różowski, Wojciech, Wild, Paul, D'Angelo, Keri, Gurke, Sebastian, Kirss, Johanna Maria, König, Barbara, Najafi, Matina, Różowski, Wojciech, and Wild, Paul

Abstract

Behavioural distances of transition systems modelled as coalgebras for endofunctors generalize the traditional notions of behavioural equivalence to a quantitative setting, in which states are equipped with a measure of how (dis)similar they are. Endowing transition systems with such distances essentially relies on the ability to lift functors describing the one-step behavior of the transition systems to the category of pseudometric spaces. We consider the Kantorovich lifting of a functor on quantale-valued relations, which subsumes equivalences, preorders and (directed) metrics. We use tools from fibred category theory, which allow one to see the Kantorovich lifting as arising from an appropriate fibred adjunction. Our main contributions are compositionality results for the Kantorovich lifting, where we show that that the lifting of a composed functor coincides with the composition of the liftings. In addition we describe how to lift distributive laws in the case where one of the two functors is polynomial. These results are essential ingredients for adopting up-to-techniques to the case of quantale-valued behavioural distances. Up-to techniques are a well-known coinductive technique for efficiently showing lower bounds for behavioural distances. We conclude by illustrating the results of our paper in two case studies.

Published
2024

19. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.

Author

Hou, Liping, Bergen, Sarah E, Akula, Nirmala, Song, Jie, Hultman, Christina M, Landén, Mikael, Adli, Mazda, Alda, Martin, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Badner, Judith A, Barrett, Thomas B, Bauer, Michael, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Berrettini, Wade H, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Bloss, Cinnamon S, Brichant-Petitjean, Clara, Bui, Elise T, Byerley, William, Cervantes, Pablo, Chillotti, Caterina, Cichon, Sven, Colom, Francesc, Coryell, William, Craig, David W, Cruceanu, Cristiana, Czerski, Piotr M, Davis, Tony, Dayer, Alexandre, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Edenberg, Howard J, Étain, Bruno, Falkai, Peter, Foroud, Tatiana, Forstner, Andreas J, Frisén, Louise, Frye, Mark A, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Gershon, Elliot S, Goes, Fernando S, Greenwood, Tiffany A, Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Heilbronner, Urs, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hipolito, Maria, Hitturlingappa, Shashi, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kelsoe, John R, Kittel-Schneider, Sarah, Kliwicki, Sebastian, Koller, Daniel L, König, Barbara, Lackner, Nina, Laje, Gonzalo, Lang, Maren, Lavebratt, Catharina, Lawson, William B, Leboyer, Marion, Leckband, Susan G, Liu, Chunyu, Maaser, Anna, Mahon, Pamela B, Maier, Wolfgang, Maj, Mario, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J, McElroy, Susan L, McInnis, Melvin G, McKinney, Rebecca, Mitchell, Philip B, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Mühleisen, Thomas W, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Tomas, Nurnberger, John I, Nwulia, Evaristus A, and Ösby, Urban

Subjects
Genetics, Mental Health, Clinical Research, Human Genome, Bipolar Disorder, Prevention, Brain Disorders, Serious Mental Illness, Mental health, Good Health and Well Being, Chromosomes, Human, X, Female, Genome-Wide Association Study, Humans, Male, Receptor, ErbB-2, Receptor, erbB-2, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P =  5.87 × 10 -  9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10 -  9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

Published
2016

20. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

Author

Hou, Liping, Heilbronner, Urs, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Banzato, Claudio EM, Benabarre, Antoni, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Bui, Elise T, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cousins, David A, Cruceanu, Cristiana, Czerski, Piotr M, Dantas, Clarissa R, Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Forstner, Andreas J, Frisén, Louise, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Jaramillo, Carlos A López, MacQueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, McCarthy, Michael J, McElroy, Susan L, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Ösby, Urban, Ozaki, Norio, Perlis, Roy H, Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A, Schofield, Peter R, Schubert, K Oliver, Schweizer, Barbara W, Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M, Smoller, Jordan W, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie, Wright, Adam, Young, L Trevor, Zandi, Peter P, Potash, James B, and DePaulo, J Raymond

Subjects
Humans, Lithium Compounds, Treatment Outcome, Prospective Studies, Bipolar Disorder, Genotype, Phenotype, Polymorphism, Single Nucleotide, Middle Aged, Female, Male, Glial Cell Line-Derived Neurotrophic Factor Receptors, Genetic Variation, Genome-Wide Association Study, Serious Mental Illness, Genetics, Mental Health, Human Genome, Brain Disorders, Genetic Testing, Mental health, Good Health and Well Being, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundLithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.MethodsHere, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.FindingsA single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0).InterpretationThe response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.FundingDeutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Published
2016

21. Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Author

Bauer, Michael, Glenn, Tasha, Achtyes, Eric D., Alda, Martin, Agaoglu, Esen, Altınbaş, Kürşat, Andreassen, Ole A., Angelopoulos, Elias, Ardau, Raffaella, Vares, Edgar Arrua, Aydin, Memduha, Ayhan, Yavuz, Baethge, Christopher, Bauer, Rita, Baune, Bernhard T., Balaban, Ceylan, Becerra-Palars, Claudia, Behere, Aniruddh P., Behere, Prakash B., Belete, Habte, Belete, Tilahun, Belizario, Gabriel Okawa, Bellivier, Frank, Belmaker, Robert H., Benedetti, Francesco, Berk, Michael, Bersudsky, Yuly, Bicakci, Şule, Birabwa-Oketcho, Harriet, Bjella, Thomas D., Brady, Conan, Cabrera, Jorge, Cappucciati, Marco, Castro, Angela Marianne Paredes, Chen, Wei-Ling, Cheung, Eric Y. Wo, Chiesa, Silvia, Crowe, Marie, Cuomo, Alessandro, Dallaspezia, Sara, Del Zompo, Maria, Desai, Pratikkumar, Dodd, Seetal, Donix, Markus, Etain, Bruno, Fagiolini, Andrea, Fellendorf, Frederike T., Ferensztajn-Rochowiak, Ewa, Fiedorowicz, Jess G., Fountoulakis, Kostas N., Frye, Mark A., Geoffroy, Pierre A., Gonzalez-Pinto, Ana, Gottlieb, John F., Grof, Paul, Haarman, Bartholomeus C. M., Harima, Hirohiko, Hasse-Sousa, Mathias, Henry, Chantal, Høffding, Lone, Houenou, Josselin, Imbesi, Massimiliano, Isometsä, Erkki T., Ivkovic, Maja, Janno, Sven, Johnsen, Simon, Kapczinski, Flávio, Karakatsoulis, Gregory N., Kardell, Mathias, Kessing, Lars Vedel, Kim, Seong Jae, König, Barbara, Kot, Timur L., Koval, Michael, Kunz, Mauricio, Lafer, Beny, Landén, Mikael, Larsen, Erik R., Lenger, Melanie, Lewitzka, Ute, Licht, Rasmus W., Lopez-Jaramillo, Carlos, MacKenzie, Alan, Madsen, Helle Østergaard, Madsen, Simone Alberte Kongstad A., Mahadevan, Jayant, Mahardika, Agustine, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Monica, Martiny, Klaus, Mashima, Yuki, McLoughlin, Declan M., Meesters, Ybe, Melle, Ingrid, Meza-Urzúa, Fátima, Ming, Mok Yee, Monteith, Scott, Moorthy, Muthukumaran, Morken, Gunnar, Mosca, Enrica, Mozzhegorov, Anton A., Munoz, Rodrigo, Mythri, Starlin V., Nacef, Fethi, Nadella, Ravi K., Nakanotani, Takako, Nielsen, René Ernst, O‘Donovan, Claire, Omrani, Adel, Osher, Yamima, Ouali, Uta, Pantovic-Stefanovic, Maja, Pariwatcharakul, Pornjira, Petite, Joanne, Pfennig, Andrea, Ruiz, Yolanda Pica, Pilhatsch, Maximilian, Pinna, Marco, Pompili, Maurizio, Porter, Richard, Quiroz, Danilo, Rabelo-da-Ponte, Francisco Diego, Ramesar, Raj, Rasgon, Natalie, Ratta-apha, Woraphat, Ratzenhofer, Michaela, Redahan, Maria, Reddy, M. S., Reif, Andreas, Reininghaus, Eva Z., Richards, Jenny Gringer, Ritter, Philipp, Rybakowski, Janusz K., Sathyaputri, Leela, Scippa, Ângela M., Simhandl, Christian, Severus, Emanuel, Smith, Daniel, Smith, José, Stackhouse, Jr., Paul W., Stein, Dan J., Stilwell, Kellen, Strejilevich, Sergio, Su, Kuan-Pin, Subramaniam, Mythily, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Tanra, Andi J., Tatebayashi, Yoshitaka, Teh, Wen Lin, Tondo, Leonardo, Torrent, Carla, Tuinstra, Daniel, Uchida, Takahito, Vaaler, Arne E., Veeh, Julia, Vieta, Eduard, Viswanath, Biju, Yoldi-Negrete, Maria, Yalcinkaya, Oguz Kaan, Young, Allan H., Zgueb, Yosra, and Whybrow, Peter C.

Published
2021
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22. HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Author

Le Clerc, Sigrid, Lombardi, Laura, Baune, Bernhard T., 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, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Ferensztajn-Rochowiak, Ewa, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Millischer, Vincent, 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., Pisanu, Claudia, 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., Spadoni, Jean-Louis, Boukouaci, Wahid, Richard, Jean-Romain, Le Corvoisier, Philippe, Barrau, Caroline, Zagury, Jean-François, Leboyer, Marion, and Tamouza, Ryad

Published
2021
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24. Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study

Author

Kelsoe, John, primary, Ou, Anna, additional, Rosenthal, Sara, additional, Adli, Mazda, additional, Akiyama, Kazufumi, additional, Akula, Nirmala, additional, Alda, Martin, additional, Amare, Azmeraw T., additional, Ardau, Raffaella, additional, Arias, Bárbara, additional, Aubry, Jean-Michel, additional, Backlund, Lena, additional, Banzato, Claudio, additional, Bauer, Michael, additional, Baune, Bernhard, additional, Bellivier, Frank, additional, Benabarre, Antonio, additional, Bengesser, Susanne, additional, Abesh, Bhattacharjee, additional, Biernacka, Joanna, additional, Bui, Elise, additional, Cervantes, Pablo, additional, Chen, Guo-Bo, additional, Chen, Hsi-Chung, additional, Chillotti, Caterina, additional, Cichon, Sven, additional, Clark, Scott, additional, Colom, Francesc, additional, Cousins, David, additional, Cruceanu, Cristiana, additional, Czerski, Piotr, additional, Dantas, Clarissa, additional, Dayer, Alexandre, additional, Degenhardt, Franziska, additional, DePaulo, J. Raymond, additional, Etain, Bruno, additional, Falkai, Peter, additional, Fellendorf, Frederike, additional, Ferensztajn-Rochowiak, Ewa, additional, Forstner, Andreas J., additional, Frisen, Louise, additional, Frye, Mark, additional, Fullerton, Janice, additional, Gard, Sebastien, additional, Garnham, Julie, additional, Goes, Fernando, additional, Grigoroiu-Serbanescu, Maria, additional, Grof, Paul, additional, Gruber, Oliver, additional, Hashimoto, Ryota, additional, Hauser, Joanna, additional, Heilbronner, Urs, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Hofmann, Andrea, additional, Hou, Liping, additional, Jamain, Stéphane, additional, Jiménez, Esther, additional, Kahn, Jean-Pierre, additional, Kassem, Layla, additional, Kato, Tadafumi, additional, Kittel-Schneider, Sarah, additional, König, Barbara, additional, kuo, Po-Hsiu, additional, Kusumi, Ichiro, additional, Dalkner, Nina, additional, Laje, Gonzalo, additional, Landén, Mikael, additional, Lavebratt, Catharina, additional, Leboyer, Marion, additional, Leckband, Susan, additional, Jaramillo, Carlos López, additional, MacQueen, Glenda, additional, Maj, Mario, additional, Manchia, Mirko, additional, Marie-Claire, Cynthia, additional, Martinsson, Lina, additional, Mattheisen, Manuel, additional, McCarthy, Michael, additional, McElroy, Susan, additional, McMahon, Francis, additional, Mitchell, Philip, additional, Mitjans, Marina, additional, Mondimore, Francis, additional, Monteleone, Palmiero, additional, Nievergelt, Caroline, additional, Nöthen, Markus, additional, Novak, Tomas, additional, Osby, Urban, additional, Ozaki, Norio, additional, Papiol, Sergi, additional, Perlis, Roy, additional, Pfennig, Andrea, additional, Potash, James, additional, Reich-Erkelenz, Daniela, additional, Reif, Andreas, additional, Reininghaus, Eva, additional, Rietschel, Marcella, additional, Rouleau, Guy, additional, Rybakowski, Janusz K., additional, Schalling, Martin, additional, Schofield, Peter, additional, Schubert, Klaus Oliver, additional, Schulze, Thomas, additional, SCHWEIZER, BARBARA, additional, Seemüller, Florian, additional, Severino, Giovanni, additional, Shekhtman, Tatyana, additional, Shilling, Paul, additional, Shimoda, Kazutaka, additional, Simhandl, Christian, additional, slaney, claire, additional, Squassina, Alessio, additional, Stamm, Thomas, additional, Stopkova, Pavla, additional, Tighe, Sarah, additional, Tortorella, Alfonso, additional, Turecki, Gustavo, additional, Vieta, Eduard, additional, Volkert, Julia, additional, Witt, Stephanie, additional, Wray, Naomi, additional, Wright, Adam, additional, Young, Trevor, additional, Zandi, Peter, additional, and Zompo, Maria Del, additional

Published
2023
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32. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder

Author

Herrera-Rivero, Marisol, primary, Gutiérrez-Fragoso, Karina, additional, Thalamuthu, Anbupalam, additional, Amare, Azmeraw T., additional, Adli, Mazda, additional, Akiyama, Kazufumi, additional, Akula, Nirmala, additional, Ardau, Raffaella, additional, Arias, Bárbara, additional, Aubry, Jean-Michel, additional, Backlund, Lena, additional, Bellivier, Frank, additional, Benabarre, Antonio, additional, Bengesser, Susanne, additional, Abesh, Bhattacharjee, additional, Biernacka, Joanna, additional, Birner, Armin, additional, Cearns, Micah, additional, Cervantes, Pablo, additional, Chen, Hsi-Chung, additional, Chillotti, Caterina, additional, Cichon, Sven, additional, Clark, Scott, additional, Colom, Francesc, additional, Cruceanu, Cristiana, additional, Czerski, Piotr, additional, Dalkner, Nina, additional, Degenhardt, Franziska, additional, Zompo, Maria Del, additional, DePaulo, J. Raymond, additional, Etain, Bruno, additional, Falkai, Peter, additional, Ferensztajn-Rochowiak, Ewa, additional, Forstner, Andreas J., additional, Frank, Josef, additional, Frisen, Louise, additional, Frye, Mark, additional, Fullerton, Janice, additional, Gallo, Carla, additional, Gard, Sebastien, additional, Garnham, Julie, additional, Goes, Fernando, additional, Grigoroiu-Serbanescu, Maria, additional, Grof, Paul, additional, Hashimoto, Ryota, additional, Hasler, Roland, additional, Hauser, Joanna, additional, Heilbronner, Urs, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Hou, Liping, additional, Hsu, YiHsiang, additional, Jamain, Stéphane, additional, Jiménez, Esther, additional, Kahn, Jean-Pierre, additional, Kassem, Layla, additional, Kato, Tadafumi, additional, Kelsoe, John, additional, Kittel-Schneider, Sarah, additional, kuo, Po-Hsiu, additional, Kurtz, Joachim, additional, Kusumi, Ichiro, additional, König, Barbara, additional, Laje, Gonzalo, additional, Landén, Mikael, additional, Lavebratt, Catharina, additional, Leboyer, Marion, additional, Leckband, Susan, additional, Maj, Mario, additional, Manchia, Mirko, additional, Marie-Claire, Cynthia, additional, Martinsson, Lina, additional, McCarthy, Michael, additional, McElroy, Susan L., additional, Millischer, Vincent, additional, Mitjans, Marina, additional, Mondimore, Francis, additional, Monteleone, Palmiero, additional, Nievergelt, Caroline, additional, Novak, Tomas, additional, Nöthen, Markus, additional, odonovan, claire, additional, Ozaki, Norio, additional, Papiol, Sergi, additional, Pfennig, Andrea, additional, Pisanu, Claudia, additional, Potash, James, additional, Reif, Andreas, additional, Reininghaus, Eva, additional, Richard-Lepouriel, Hélène, additional, Roberts, Gloria, additional, Rouleau, Guy, additional, Rybakowski, Janusz K., additional, Schalling, Martin, additional, Schofield, Peter, additional, Schubert, Klaus Oliver, additional, Schulte, Eva, additional, SCHWEIZER, BARBARA, additional, Severino, Giovanni, additional, Shekhtman, Tatyana, additional, Shilling, Paul, additional, Shimoda, Kazutaka, additional, Simhandl, Christian, additional, slaney, claire, additional, Squassina, Alessio, additional, Stamm, Thomas, additional, Stopkova, Pavla, additional, Streit, Fabian, additional, Ayele, Fasil, additional, Tortorella, Alfonso, additional, Turecki, Gustavo, additional, Veeh, Julia, additional, Vieta, Eduard, additional, Viswanath, Biju, additional, Witt, Stephanie, additional, Zandi, Peter, additional, Alda, Martin, additional, Bauer, Michael, additional, McMahon, Francis, additional, Mitchell, Philip, additional, Rietschel, Marcella, additional, Schulze, Thomas, additional, and Baune, Bernhard, additional

Published
2023
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34. Heat vs. Health: Home Office under a Changing Climate

Author

Schaffernicht, Sophie Kathrin, primary, Türk, Andreas, additional, Kogler, Martha, additional, Berger, Andreas, additional, Scharf, Bernhard, additional, Clementschitsch, Lukas, additional, Hammer, Renate, additional, Holzer, Peter, additional, Formayer, Herbert, additional, König, Barbara, additional, and Haluza, Daniela, additional

Published
2023
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36. Hennessy-Milner Theorems via Galois Connections

Author

Harsh Beohar and Sebastian Gurke and Barbara König and Karla Messing, Beohar, Harsh, Gurke, Sebastian, König, Barbara, Messing, Karla, Harsh Beohar and Sebastian Gurke and Barbara König and Karla Messing, Beohar, Harsh, Gurke, Sebastian, König, Barbara, and Messing, Karla

Abstract

We introduce a general and compositional, yet simple, framework that allows to derive soundness and expressiveness results for modal logics characterizing behavioural equivalences or metrics (also known as Hennessy-Milner theorems). It is based on Galois connections between sets of (real-valued) predicates on the one hand and equivalence relations/metrics on the other hand and covers a part of the linear-time-branching-time spectrum, both for the qualitative case (behavioural equivalences) and the quantitative case (behavioural metrics). We derive behaviour functions from a given logic and give a condition, called compatibility, that characterizes under which conditions a logically induced equivalence/metric is induced by a fixpoint equation. In particular, this framework allows to derive a new fixpoint characterization of directed trace metrics.

Published
2023
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37. A Lattice-Theoretical View of Strategy Iteration

Author

Paolo Baldan and Richard Eggert and Barbara König and Tommaso Padoan, Baldan, Paolo, Eggert, Richard, König, Barbara, Padoan, Tommaso, Paolo Baldan and Richard Eggert and Barbara König and Tommaso Padoan, Baldan, Paolo, Eggert, Richard, König, Barbara, and Padoan, Tommaso

Abstract

Strategy iteration is a technique frequently used for two-player games in order to determine the winner or compute payoffs, but to the best of our knowledge no general framework for strategy iteration has been considered. Inspired by previous work on simple stochastic games, we propose a general formalisation of strategy iteration for solving least fixpoint equations over a suitable class of complete lattices, based on MV-chains. We devise algorithms that can be used for non-expansive fixpoint functions represented as so-called min- respectively max-decompositions. Correspondingly, we develop two different techniques: strategy iteration from above, which has to solve the problem that iteration might reach a fixpoint that is not the least, and from below, which is algorithmically simpler, but requires a more involved correctness argument. We apply our method to solve energy games and compute behavioural metrics for probabilistic automata.

Published
2023
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38. Quantitative Graded Semantics and Spectra of Behavioural Metrics

Author

Forster, Jonas, Schröder, Lutz, Wild, Paul, Beohar, Harsh, Gurke, Sebastian, König, Barbara, Messing, Karla, Forster, Jonas, Schröder, Lutz, Wild, Paul, Beohar, Harsh, Gurke, Sebastian, König, Barbara, and Messing, Karla

Abstract

Behavioural metrics provide a quantitative refinement of classical two-valued behavioural equivalences on systems with quantitative data, such as metric or probabilistic transition systems. In analogy to the linear-time/branching-time spectrum of two-valued behavioural equivalences on transition systems, behavioural metrics vary in granularity. We provide a unifying treatment of spectra of behavioural metrics in the emerging framework of graded monads, working in coalgebraic generality, that is, parametrically in the system type. In the ensuing development of quantitative graded semantics, we introduce algebraic presentations of graded monads on the category of metric spaces. Moreover, we obtain a canonical generic notion of invariant real-valued modal logic, and provide criteria for such logics to be expressive in the sense that logical distance coincides with behavioural distance. We present positive examples based on this criterion, covering both known and new expressiveness results; in particular, we show that expressiveness holds essentially always for Eilenberg-Moore type trace semantics, and we obtain a new expressiveness result for trace semantics of fuzzy transition systems. As a negative result, we show that trace distance on probabilistic metric transition systems does not admit any characteristic real-valued modal logic, even in a more broadly understood sense.

Published
2023

39. A Monoidal View on Fixpoint Checks

Author

Baldan, Paolo, Eggert, Richard, König, Barbara, Matt, Timo, Padoan, Tommaso, Baldan, Paolo, Eggert, Richard, König, Barbara, Matt, Timo, and Padoan, Tommaso

Abstract

Fixpoints are ubiquitous in computer science as they play a central role in providing a meaning to recursive and cyclic definitions. Bisimilarity, behavioural metrics, termination probabilities for Markov chains and stochastic games are defined in terms of least or greatest fixpoints. Here we show that our recent work which proposes a technique for checking whether the fixpoint of a function is the least (or the largest) admits a natural categorical interpretation in terms of gs-monoidal categories. The technique is based on a construction that maps a function to a suitable approximation and the compositionality properties of this mapping are naturally interpreted as a gs-monoidal functor. This guides the realisation of a tool, called UDEfix that allows to build functions (and their approximations) like a circuit out of basic building blocks and subsequently perform the fixpoints checks. We also show that a slight generalisation of the theory allows one to treat a new relevant case study: coalgebraic behavioural metrics based on Wasserstein liftings.

Published
2023

40. Interpretable Anomaly Detection via Discrete Optimization

Author

Lutz, Simon, Wittbold, Florian, Dierl, Simon, Böing, Benedikt, Howar, Falk, König, Barbara, Müller, Emmanuel, Neider, Daniel, Lutz, Simon, Wittbold, Florian, Dierl, Simon, Böing, Benedikt, Howar, Falk, König, Barbara, Müller, Emmanuel, and Neider, Daniel

Abstract

Anomaly detection is essential in many application domains, such as cyber security, law enforcement, medicine, and fraud protection. However, the decision-making of current deep learning approaches is notoriously hard to understand, which often limits their practical applicability. To overcome this limitation, we propose a framework for learning inherently interpretable anomaly detectors from sequential data. More specifically, we consider the task of learning a deterministic finite automaton (DFA) from a given multi-set of unlabeled sequences. We show that this problem is computationally hard and develop two learning algorithms based on constraint optimization. Moreover, we introduce novel regularization schemes for our optimization problems that improve the overall interpretability of our DFAs. Using a prototype implementation, we demonstrate that our approach shows promising results in terms of accuracy and F1 score.

Published
2023

41. Stochastic Decision Petri Nets

Author

Wittbold, Florian, Bernemann, Rebecca, Heckel, Reiko, Heindel, Tobias, König, Barbara, Wittbold, Florian, Bernemann, Rebecca, Heckel, Reiko, Heindel, Tobias, and König, Barbara

Abstract

We introduce stochastic decision Petri nets (SDPNs), which are a form of stochastic Petri nets equipped with rewards and a control mechanism via the deactivation of controllable transitions. Such nets can be translated into Markov decision processes (MDPs), potentially leading to a combinatorial explosion in the number of states due to concurrency. Hence we restrict ourselves to instances where nets are either safe, free-choice and acyclic nets (SAFC nets) or even occurrence nets and policies are defined by a constant deactivation pattern. We obtain complexity-theoretic results for such cases via a close connection to Bayesian networks, in particular we show that for SAFC nets the question whether there is a policy guaranteeing a reward above a certain threshold is $\mathsf{NP}^\mathsf{PP}$-complete. We also introduce a partial-order procedure which uses an SMT solver to address this problem.

Published
2023

42. Expressive Quantale-valued Logics for Coalgebras: an Adjunction-based Approach

Author

Beohar, Harsh, Gurke, Sebastian, König, Barbara, Messing, Karla, Forster, Jonas, Schröder, Lutz, Wild, Paul, Beohar, Harsh, Gurke, Sebastian, König, Barbara, Messing, Karla, Forster, Jonas, Schröder, Lutz, and Wild, Paul

Abstract

We address the task of deriving fixpoint equations from modal logics characterizing behavioural equivalences and metrics (summarized under the term conformances). We rely on earlier work that obtains Hennessy-Milner theorems as corollaries to a fixpoint preservation property along Galois connections between suitable lattices. We instantiate this to the setting of coalgebras, in which we spell out the compatibility property ensuring that we can derive a behaviour function whose greatest fixpoint coincides with the logical conformance. We then concentrate on the linear-time case, for which we study coalgebras based on the machine functor living in Eilenberg-Moore categories, a scenario for which we obtain a particularly simple logic and fixpoint equation. The theory is instantiated to concrete examples, both in the branching-time case (bisimilarity and behavioural metrics) and in the linear-time case (trace equivalences and trace distances).

Published
2023

47. Changes in Community Composition and Functional Traits of Bumblebees in an Alpine Ecosystem Relate to Climate Warming

Author

Scharnhorst, Victor Sebastian, primary, Thierolf, Katharina, additional, Neumayer, Johann, additional, Becsi, Benedikt, additional, Formayer, Herbert, additional, Lanner, Julia, additional, Ockermüller, Esther, additional, Mirwald, Alina, additional, König, Barbara, additional, Kriechbaum, Monika, additional, Meimberg, Harald, additional, Meyer, Philipp, additional, Rupprecht, Christina, additional, and Pachinger, Bärbel, additional

Published
2023
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48. Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder

Author

Amare, Azmeraw, primary, Thalamuthu, Anbupalam, additional, Schubert, Klaus Oliver, additional, Fullerton, Janice, additional, Ahmed, Muktar, additional, Hartmann, Simon, additional, Papiol, Sergi, additional, Heilbronner, Urs, additional, Degenhardt, Franziska, additional, Tekola-Ayele, Fasil, additional, Hou, Liping, additional, Hsu, Yi-Hsiang, additional, Shekhtman, Tatyana, additional, Adli, Mazda, additional, Akula, Nirmala, additional, Akiyama, Kazufumi, additional, Ardau, Raffaella, additional, Arias, Bárbara, additional, Aubry, Jean-Michel, additional, Backlund, Lena, additional, Bhattacharjee, Abesh Kumar, additional, Bellivier, Frank, additional, Benabarre, Antoni, additional, Bengesser, Susanne, additional, Biernacka, Joanna, additional, Birner, Armin, additional, Marie-Claire, Cynthia, additional, Cervantes, Pablo, additional, Chen, Hsi-Chung, additional, Chillotti, Caterina, additional, Cichon, Sven, additional, Cruceanu, Cristiana, additional, Czerski, Piotr, additional, Dalkner, Nina, additional, Zompo, Maria Del, additional, DePaulo, J. Raymond, additional, Etain, Bruno, additional, Jamain, Stéphane, additional, Falkai, Peter, additional, Forstner, Andreas J., additional, Frisén, Louise, additional, Frye, Mark, additional, Gard, Sébastien, additional, Garnham, Julie, additional, Goes, Fernando, additional, Grigoroiu-Serbanescu, Maria, additional, Fallgatter, Andreas, additional, Stegmaier, Sophia, additional, Ethofer, Thomas, additional, Biere, Silvia, additional, Petrova, Kristiyana, additional, Schuster, Ceylan, additional, Adorjan, Kristina, additional, Budde, Monika, additional, Heilbronner, Maria, additional, Kalman, Janos, additional, Kohshour, Mojtaba Oraki, additional, Reich-Erkelenz, Daniela, additional, Schaupp, Sabrina, additional, Schulte, Eva, additional, Senner, Fanny, additional, Vogl, Thomas, additional, Anghelescu, Ion-George, additional, Arolt, Volker, additional, Dannlowski, Udo, additional, Dietrich, Detlef E., additional, Figge, Christian, additional, Jäger, Markus, additional, Lang, Fabian, additional, Juckel, Georg, additional, Spitzer, Carsten, additional, Reimer, Jens, additional, Schmauß, Max, additional, Schmitt, Andrea, additional, Konrad, Carsten, additional, von Hagen, Martin, additional, Wiltfang, Jens, additional, Zimmermann, Jörg, additional, Andlauer, Till, additional, Fischer, Andre, additional, Bermpohl, Felix, additional, Kraft, Vivien, additional, Matura, Silke, additional, Gryaznova, Anna, additional, Falkenberg, Irina, additional, Yildiz, Cüneyt, additional, Kircher, Tilo, additional, Schmidt, Julia, additional, Koch, Marius, additional, Gade, Katrin, additional, Trost, Sarah, additional, Haußleiter, Ida, additional, Lambert, Martin, additional, Rohenkohl, Anja C., additional, Grof, Paul, additional, Hashimoto, Ryota, additional, Hauser, Joanna, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Jiménez, Esther, additional, Kahn, Jean-Pierre, additional, Kassem, Layla, additional, kuo, Po-Hsiu, additional, Kato, Tadafumi, additional, Kelsoe, John, additional, Kittel-Schneider, Sarah, additional, Ferensztajn-Rochowiak, Ewa, additional, König, Barbara, additional, Kusumi, Ichiro, additional, Laje, Gonzalo, additional, Landén, Mikael, additional, Lavebratt, Catharina, additional, Leboyer, Marion, additional, Leckband, Susan G., additional, Tortorella, Alfonso, additional, Manchia, Mirko, additional, Martinsson, Lina, additional, McCarthy, Michael, additional, McElroy, Susan L., additional, Colom, Francesc, additional, Mitjans, Marina, additional, Mondimore, Francis, additional, Monteleone, Palmiero, additional, Nievergelt, Caroline, additional, Nöthen, Markus, additional, Novak, Tomas, additional, O'Donovan, Claire, additional, Ozaki, Norio, additional, Pfennig, Andrea, additional, Pisanu, Claudia, additional, Potash, James, additional, Reif, Andreas, additional, Reininghaus, Eva, additional, Rouleau, Guy, additional, Rybakowski, Janusz K., additional, Schalling, Martin, additional, Schofield, Peter, additional, Schweizer, Barbara W., additional, Severino, Giovanni, additional, Shilling, Paul D, additional, Shimoda, Kazutaka, additional, Simhandl, Christian, additional, Slaney, Claire, additional, Squassina, Alessio, additional, Stamm, Thomas, additional, Stopkova, Pavla, additional, Maj, Mario, additional, Turecki, Gustavo, additional, Vieta, Eduard, additional, Veeh, Julia, additional, Witt, Stephanie, additional, Wright, Adam, additional, Zandi, Peter, additional, Mitchell, Philip, additional, Bauer, Michael, additional, Alda, Martin, additional, Rietschel, Marcella, additional, McMahon, Francis, additional, Schulze, Thomas G., additional, Millischer, Vincent, additional, Clark, Scott, additional, and Baune, Bernhard, additional

Published
2023
Full Text
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49. A Lattice-Theoretical View of Strategy Iteration

Author

Baldan, Paolo, Eggert, Richard, König, Barbara, and Padoan, Tommaso

Subjects
FOS: Computer and information sciences, behavioural metrics, Computer Science - Logic in Computer Science, Informatik, strategy iteration, fixpoints, Theory of computation → Program verification, Theory of computation → Solution concepts in game theory, energy games, games, Logic in Computer Science (cs.LO)
Abstract

Strategy iteration is a technique frequently used for two-player games in order to determine the winner or compute payoffs, but to the best of our knowledge no general framework for strategy iteration has been considered. Inspired by previous work on simple stochastic games, we propose a general formalisation of strategy iteration for solving least fixpoint equations over a suitable class of complete lattices, based on MV-chains. We devise algorithms that can be used for non-expansive fixpoint functions represented as so-called min- respectively max-decompositions. Correspondingly, we develop two different techniques: strategy iteration from above, which has to solve the problem that iteration might reach a fixpoint that is not the least, and from below, which is algorithmically simpler, but requires a more involved correctness argument. We apply our method to solve energy games and compute behavioural metrics for probabilistic automata., LIPIcs, Vol. 252, 31st EACSL Annual Conference on Computer Science Logic (CSL 2023), pages 7:1-7:19

Published
2023

50. Fixpoint Theory : Upside Down

Author

Baldan, Paolo, Eggert, Richard, König, Barbara, and Padoan, Tommaso

Subjects
FOS: Computer and information sciences, Discrete mathematics, Computer Science - Logic in Computer Science, Monotonic function, 010103 numerical & computational mathematics, 0102 computer and information sciences, Fixed point, 01 natural sciences, Article, Logic in Computer Science (cs.LO), Informatik, Monotone polygon, Complete lattice, 010201 computation theory & mathematics, Simple (abstract algebra), Computer Science::Logic in Computer Science, Computer Science::Programming Languages, Finitary, 0101 mathematics, Element (category theory), Finite set, Mathematics
Abstract

Knaster-Tarski’s theorem, characterising the greatest fix- point of a monotone function over a complete lattice as the largest post-fixpoint, naturally leads to the so-called coinduction proof principle for showing that some element is below the greatest fixpoint (e.g., for providing bisimilarity witnesses). The dual principle, used for showing that an element is above the least fixpoint, is related to inductive invariants. In this paper we provide proof rules which are similar in spirit but for showing that an element is above the greatest fixpoint or, dually, below the least fixpoint. The theory is developed for non-expansive monotone functions on suitable lattices of the form$$\mathbb {M}^Y$$MY, whereYis a finite set and$$\mathbb {M}$$Man MV-algebra, and it is based on the construction of (finitary) approximations of the original functions. We show that our theory applies to a wide range of examples, including termination probabilities, behavioural distances for probabilistic automata and bisimilarity. Moreover it allows us to determine original algorithms for solving simple stochastic games.

Published
2023

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