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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. The impact of school-based screening on service use in adolescents at risk for mental health problems and risk-behaviour

Author

Lustig, Sophia, Kaess, Michael, Schnyder, Nina, Michel, Chantal, Brunner, Romuald, Tubiana, Alexandra, Kahn, Jean-Pierre, Sarchiapone, Marco, Hoven, Christina W., Barzilay, Shira, Apter, Alan, Balazs, Judit, Bobes, Julio, Saiz, Pilar Alejandra, Cozman, Doina, Cotter, Padraig, Kereszteny, Agnes, Podlogar, Tina, Postuvan, Vita, Värnik, Airi, Resch, Franz, Carli, Vladimir, and Wasserman, Danuta

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

8. 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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10. Doing Nothing Is Sometimes Worse: Comparing Avoidant versus Approach Coping Strategies with Peer Victimization and Their Association to Depression and Suicide Ideation

Author

Benatov, Joy, Klomek, Anat Brunstein, Shira, Barzilay, Apter, Alan, Carli, Vladimir, Wasserman, Camilla, Hoven, Christina W., Sarchiapone, Marco, Balazs, Juit, Bobes, Julio, Brunner, Romuald, Corcoran, Paul, Cosman, Doina, Haring, Christian, Kahn, Jean-Pierre, Keeley, Helen, Kereszteny, Agnes, Podlogar, Tina, Postuvan, Vita, Saiz, Pilar A., Sisask, Merike, Varnik, Airi, and Wasserman, Danuta

Abstract

Peer victimization is a major stressor adolescents often face in the school environment, and has been linked to depression and suicidal risk. This study analyzed the associations between three behavioral coping strategies (avoidance, seeking social support from adults/peers, and retaliation) and depression and suicidal ideation. Participants included 4,254 victimized students who were part of the Saving and Empowering Young Lives in Europe (SEYLE) study that compared three school-based prevention interventions and collected information on health risk behaviors in adolescents from 11 European countries. Results showed behavioral avoidance to be associated with an increase in levels of depression, as compared to the other coping strategies (adult social support, peer social support, retaliation). Seeking social support from adults was associated with lower depression and suicidal ideation rates. A more than 25% increase in suicidal ideation was associated with behavioral avoidance, compared to seeking social support from adults. By contrast, retaliation to peer victimization was not found to be associated with increased depression or suicidal ideation. The findings support the Coping Deficit model and may suggest that abstaining by doing nothing when victimized can be associated with certain adverse emotional outcomes.

Published
2020
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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. Excessive and pathological Internet use – Risk-behavior or psychopathology?

Author

Kaess, Michael, Klar, Johanna, Kindler, Jochen, Parzer, Peter, Brunner, Romuald, Carli, Vladimir, Sarchiapone, Marco, Hoven, Christina W., Apter, Alan, Balazs, Judit, Barzilay, Shira, Bobes, Julio, Cozman, Doina, Gomboc, Vanja, Haring, Christian, Kahn, Jean-Pierre, Keeley, Helen, Meszaros, Gergely, Musa, George J., Postuvan, Vita, Saiz, Pilar, Sisask, Merike, Varnik, Peeter, Resch, Franz, and Wasserman, Danuta

Published
2021
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15. Life Events Predicting the First Onset of Adolescent Direct Self-Injurious Behavior—A Prospective Multicenter Study

Author

Kaess, Michael, Eppelmann, Lena, Brunner, Romuald, Parzer, Peter, Resch, Franz, Carli, Vladimir, Wasserman, Camilla, Sarchiapone, Marco, Hoven, Christina W., Apter, Alan, Balazs, Judit, Barzilay, Shila, Bobes, Julio, Cosman, Doina, Horvath, Lili O., Kahn, Jean-Pierre, Keeley, Helen, McMahon, Elaine, Podlogar, Tina, Postuvan, Vita, Saiz, Pilar A., Tubiana, Alexandra, Varnik, Airi, and Wasserman, Danuta

Published
2020
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16. 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

17. 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

18. Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance

Author

Li, Ming, Luo, Xiong-jian, Landén, Mikael, Bergen, Sarah E, Hultman, Christina M, Li, Xiao, Zhang, Wen, Yao, Yong-Gang, Zhang, Chen, Liu, Jiewei, Mattheisen, Manuel, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska A, Nöthen, Markus M, Schulze, Thomas G, Grigoroiu-Serbanescu, Maria, Li, Hao, Fuller, Chris K, Chen, Chunhui, Dong, Qi, Chen, Chuansheng, Jamain, Stéphane, Leboyer, Marion, Bellivier, Frank, Etain, Bruno, Kahn, Jean-Pierre, Henry, Chantal, Preisig, Martin, Kutalik, Zoltán, Castelao, Enrique, Wright, Adam, Mitchell, Philip B, Fullerton, Janice M, Schofield, Peter R, Montgomery, Grant W, Medland, Sarah E, Gordon, Scott D, Martin, Nicholas G, Rietschel, Marcella, Liu, Chunyu, Kleinman, Joel E, Hyde, Thomas M, Weinberger, Daniel R, and Su, Bing

Subjects
Biological Psychology, Epidemiology, Health Sciences, Psychology, Serious Mental Illness, Neurosciences, Mental Health, Brain Disorders, Human Genome, Genetics, Clinical Research, Prevention, 2.1 Biological and endogenous factors, Aetiology, Mental health, Aged, Bayes Theorem, Bipolar Disorder, Case-Control Studies, Chromosomes, Human, Pair 22, Cognition, Genetic Predisposition to Disease, Genome-Wide Association Study, Hippocampus, Humans, Logistic Models, Polymorphism, Single Nucleotide, MooDS Consortium, Swedish Bipolar Study Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biomedical and clinical sciences, Health sciences
Abstract

BACKGROUND:Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. AIMS:We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. METHOD:To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. RESULTS:Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85 × 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54 × 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. CONCLUSIONS:Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Published
2016

19. 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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20. Influence of coping strategies on the efficacy of YAM (Youth Aware of Mental Health): a universal school-based suicide preventive program

Author

Kahn, Jean-Pierre, Cohen, Renaud F., Tubiana, Alexandra, Legrand, Karine, Wasserman, Camilla, Carli, Vladimir, Apter, Alan, Balazs, Judit, Banzer, Raphaele, Baralla, Francesca, Barzilai, Shira, Bobes, Julio, Brunner, Romuald, Corcoran, Paul, Cosman, Doina, Guillemin, Francis, Haring, Christian, Kaess, Michael, Bitenc, Urša Mars, Mészàros, Gergley, McMahon, Elaine, Postuvan, Vita, Saiz, Pilar, Varnik, Airi, Varnik, Peeter, Sarchiapone, Marco, Hoven, Christina W., and Wasserman, Danuta

Published
2020
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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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28. A cost-effectiveness analysis of school-based suicide prevention programmes

Author

Ahern, Susan, Burke, Lee-Ann, McElroy, Brendan, Corcoran, Paul, McMahon, Elaine M., Keeley, Helen, Carli, Vladimir, Wasserman, Camilla, Hoven, Christina W., Sarchiapone, Marco, Apter, Alan, Balazs, Judit, Banzer, Raphaela, Bobes, Julio, Brunner, Romuald, Cosman, Doina, Haring, Christian, Kaess, Michael, Kahn, Jean-Pierre, Kereszteny, Agnes, Postuvan, Vita, Sáiz, Pilar A., Varnik, Peeter, and Wasserman, Danuta

Published
2018
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30. 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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31. Bullying Victimization and Suicide Ideation and Behavior Among Adolescents in Europe: A 10-Country Study

Author

Barzilay, Shira, Brunstein Klomek, Anat, Apter, Alan, Carli, Vladimir, Wasserman, Camilla, Hadlaczky, Gergö, Hoven, Christina W., Sarchiapone, Marco, Balazs, Judit, Kereszteny, Agnes, Brunner, Romuald, Kaess, Michael, Bobes, Julio, Saiz, Pilar, Cosman, Doina, Haring, Christian, Banzer, Raphaela, Corcoran, Paul, Kahn, Jean-Pierre, Postuvan, Vita, Podlogar, Tina, Sisask, Merike, Varnik, Airi, and Wasserman, Danuta

Published
2017
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35. 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
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36. Suicide prevention strategies revisited: 10-year systematic review

Author

Zalsman, Gil, Hawton, Keith, Wasserman, Danuta, van Heeringen, Kees, Arensman, Ella, Sarchiapone, Marco, Carli, Vladimir, Höschl, Cyril, Barzilay, Ran, Balazs, Judit, Purebl, György, Kahn, Jean Pierre, Sáiz, Pilar Alejandra, Lipsicas, Cendrine Bursztein, Bobes, Julio, Cozman, Doina, Hegerl, Ulrich, and Zohar, Joseph

Published
2016
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39. School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial

Author

Wasserman, Danuta, Hoven, Christina W, Wasserman, Camilla, Wall, Melanie, Eisenberg, Ruth, Hadlaczky, Gergö, Kelleher, Ian, Sarchiapone, Marco, Apter, Alan, Balazs, Judit, Bobes, Julio, Brunner, Romuald, Corcoran, Paul, Cosman, Doina, Guillemin, Francis, Haring, Christian, Iosue, Miriam, Kaess, Michael, Kahn, Jean-Pierre, Keeley, Helen, Musa, George J, Nemes, Bogdan, Postuvan, Vita, Saiz, Pilar, Reiter-Theil, Stella, Varnik, Airi, Varnik, Peeter, and Carli, Vladimir

Published
2015
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43. Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1

Author

Chang, Hong, Li, Lingyi, Peng, Tao, Grigoroiu-Serbanescu, Maria, Bergen, Sarah E., Landén, Mikael, Hultman, Christina M., Forstner, Andreas J., Strohmaier, Jana, Hecker, Julian, Schulze, Thomas G., Müller-Myhsok, Bertram, Reif, Andreas, Mitchell, Philip B., Martin, Nicholas G., Cichon, Sven, Nöthen, Markus M., Jamain, Stéphane, Leboyer, Marion, Bellivier, Frank, Etain, Bruno, Kahn, Jean-Pierre, Henry, Chantal, Rietschel, Marcella, Xiao, Xiao, Li, Ming, Backlund, Lena, Frisén, Louise, Lavebratt, Catharina, Schalling, Martin, Ösby, Urban, Mühleisen, Thomas W., Leber, Markus, Degenhardt, Franziska, Treutlein, Jens, Mattheisen, Manuel, Hofmann, Andrea, Breuer, René, Meier, Sandra, Herms, Stefan, Hoffmann, Per, Lacour, André, Witt, Stephanie H., Streit, Fabian, Lucae, Susanne, Maier, Wolfgang, Schwarz, Markus, Vedder, Helmut, Kammerer-Ciernioch, Jutta, Pfennig, Andrea, Bauer, Michael, Hautzinger, Martin, Wright, Adam, Fullerton, Janice M., Schofield, Peter R., Montgomery, Grant W., Medland, Sarah E., Gordon, Scott D., Becker, Tim, Schumacher, Johannes, Propping, Peter, The Swedish Bipolar Study Group, and MooDS Consortium

Published
2017
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44. Physical activity in European adolescents and associations with anxiety, depression and well-being

Author

McMahon, Elaine M., Corcoran, Paul, O’Regan, Grace, Keeley, Helen, Cannon, Mary, Carli, Vladimir, Wasserman, Camilla, Hadlaczky, Gergö, Sarchiapone, Marco, Apter, Alan, Balazs, Judit, Balint, Maria, Bobes, Julio, Brunner, Romuald, Cozman, Doina, Haring, Christian, Iosue, Miriam, Kaess, Michael, Kahn, Jean-Pierre, Nemes, Bogdan, Podlogar, Tina, Poštuvan, Vita, Sáiz, Pilar, Sisask, Merike, Tubiana, Alexandra, Värnik, Peeter, Hoven, Christina W., and Wasserman, Danuta

Published
2017
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45. Teacher Satisfaction with School and Psychological Well-Being Affects Their Readiness to Help Children with Mental Health Problems

Author

Sisask, Merike, Värnik, Peeter, Värnik, Airi, Apter, Alan, Balazs, Judit, Balint, Maria, Bobes, Julio, Brunner, Romuald, Corcoran, Paul, Cosman, Doina, Feldman, Dana, Haring, Christian, Kahn, Jean-Pierre, Poštuvan, Vita, Tubiana, Alexandra, Sarchiapone, Marco, Wasserman, Camilla, Carli, Vladimir, Hoven, Christina W., and Wasserman, Danuta

Abstract

Objective: In support of a whole-school approach to mental health promotion, this study was conducted to find out whether and how significantly teachers' satisfaction with school and their subjective psychological well-being are related to the belief that they can help pupils with mental health problems. Design: Cross-sectional data were collected as a part of the European Union's, Seventh Framework Programme for Research (FP7) Saving and Empowering Young Lives in Europe (SEYLE) study. One of the elements of the SEYLE study was to evaluate teachers' attitudes and knowledge related to pupils' mental health issues and their own psychological well-being, as well as their satisfaction with the school environment. Setting: The sample of schools from the SEYLE study sites representing 11 European countries was randomly chosen according to prior defined inclusion and exclusion criteria. The final cross-sectional database used for analysis in the current study comprised 2485 teachers from 158 randomly selected schools. Method: Respondents' belief that teachers can help pupils with mental health problems served as the outcome variable in our predictions with probability of the positive answer being modelled in the logistic regression analysis. Teachers' subjective psychological well-being and school satisfaction were included as independent variables in the logistic regression model and several other relevant variables were added to statistically control for them. Multiple models were tested in order to obtain the final modResults: Logistic regression models showed that better satisfaction with general school climate, higher psychological well-being, and the ability to understand pupils' mental health problems increased the odds of teachers' readiness to help pupils with mental health problems. Conclusion: By providing a good school environment, by valuing the subjective psychological well-being of the teachers, and by providing adequate training to fulfil their 'gatekeeper' role, the preconditions to improve the mental health of the pupils they teach will be achieved. These suggestions are in line with a whole-school approach to mental health promotion.

Published
2014
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46. Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

Author

Li, Ming, Huang, Liang, Grigoroiu-Serbanescu, Maria, Bergen, Sarah E., Landén, Mikael, Hultman, Christina M., Forstner, Andreas J., Strohmaier, Jana, Hecker, Julian, Schulze, Thomas G., Müller-Myhsok, Bertram, Reif, Andreas, Mitchell, Philip B., Martin, Nicholas G., Cichon, Sven, Nöthen, Markus M., Alkelai, Anna, Lerer, Bernard, Jamain, Stéphane, Leboyer, Marion, Bellivier, Frank, Etain, Bruno, Kahn, Jean-Pierre, Henry, Chantal, Rietschel, Marcella, MooDS Consortium, and The Swedish Bipolar Study Group

Published
2016
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47. Association between victimization by bullying and direct self injurious behavior among adolescence in Europe: a ten-country study

Author

Brunstein Klomek, Anat, Snir, Avigal, Apter, Alan, Carli, Vladimir, Wasserman, Camilla, Hadlaczky, Gergö, Hoven, Christina W., Sarchiapone, Marco, Balazs, Judit, Bobes, Julio, Brunner, Romuald, Corcoran, Paul, Cosman, Doina, Haring, Christian, Kahn, Jean-Pierre, Kaess, Michael, Postuvan, Vita, Sisask, Merike, Tubiana, Alexandra, Varnik, Airi, Žiberna, Janina, and Wasserman, Danuta

Published
2016
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49. Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: Machine learning approach

Author

Cearns, Micah, Amare, Azmeraw, Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Frank, Joseph, Streit, Fabian, 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, Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Zompo, Maria Del, Depaulo, J Raymond, Étain, Bruno, Falkai, Peter, Forstner, Andreas, Frisen, Louise, Frye, Mark, Fullerton, Janice, Gard, Sébastien, Garnham, Julie, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael, Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis, Monteleone, Palmiero, Nievergelt, Caroline, Nöthen, Markus, Novák, Tomas, O'Donovan, Claire, Ozaki, Norio, Millischer, Vincent, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James, Reif, Andreas, Reininghaus, Eva, Rouleau, Guy, Rybakowski, Janusz, Schalling, Martin, Schofield, Peter, Schweizer, Barbara, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tekola-Ayele, Fasil, Tortorella, Alfonso, Turecki, Gustavo, Veeh, Julia, Vieta, Eduard, Witt, Stephanie, Roberts, Gloria, Zandi, Peter, Alda, Martin, Bauer, Michael, Mcmahon, Francis, Mitchell, Philip, Schulze, Thomas, Rietschel, Marcella, Clark, Scott, Baune, Bernhard, Cearns, Micah, Amare, Azmeraw T, Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Frank, Joseph, Streit, Fabian, 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, Degenhardt, Franziska, Zompo, Maria Del, 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, Ur, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, 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, Toma, O'Donovan, Claire, Ozaki, Norio, Millischer, Vincent, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Reif, Andrea, 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, Thoma, 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, Clark, Scott R, Baune, Bernhard T, Etain, Bruno, University of South Australia [Adelaide], South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, University Medical Center Heidelberg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], National Institute of Mental Health (NIMH), National Institutes of Health [Bethesda] (NIH), Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), University of Barcelona, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Karolinska Institute, Karolinska University Hospital [Stockholm], University of California [San Diego] (UC San Diego), University of California (UC), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Medical University of Graz, Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University of Bonn, University Hospital Basel [Basel], Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Ludwig Maximilian University [Munich] (LMU), University of Basel (Unibas), Karolinska Institutet [Stockholm], University of New South Wales [Sydney] (UNSW), Centre hospitalier Charles Perrens [Bordeaux], Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Georg-August-University = Georg-August-Universität Göttingen, University Medical Center Göttingen (UMG), Institute of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians-Universität München (LMU), Harvard School of Public Health, Harvard Medical School [Boston] (HMS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Psychothérapique de Nancy [Laxou] (CPN), Juntendo University, Frankfurt University Hospital, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], VA San Diego Healthcare System [San Diego, CA, USA] (VASDHS), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Instituto de Salud Carlos III [Madrid] (ISC), Università degli Studi di Salerno = University of Salerno (UNISA), National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University, Medizinische Universität Wien = Medical University of Vienna, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Montreal Neurological Institute and Hospital, Neuroscience Research Australia (NeuRA), Sigmund Freud University (SFU), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Università degli Studi di Perugia = University of Perugia (UNIPG), Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg], Johns Hopkins Bloomberg School of Public Health [Baltimore], University Medical Center, University of Adelaide, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, and The Florey Institute of Neuroscience and Mental Health

Subjects
Psychiatry and Mental health, depressive disorder, bipolar affective disorder, outcome studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Mood stabiliser, Mood stabilisers, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, genetics, genetic, depressive disorders, bipolar affective disorders
Abstract

BackgroundResponse to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Published
2022

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