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

Author

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

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

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

Published
2023

2. 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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3. 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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6. 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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7. Characterisation of age and polarity at onset in bipolar disorder.

Author

Kalman, Janos L, Olde Loohuis, Loes M, Vreeker, Annabel, McQuillin, Andrew, Stahl, Eli A, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim B, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark J, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie R, Anderson-Schmidt, Heike, Andreassen, Ole A, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade H, Boks, Marco P, Bromet, Evelyn J, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott R, Comes, Ashley L, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David W, Croarkin, Paul E, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard J, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman H, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas J, Frye, Mark A, Fullerton, Janice M, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando S, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene S, Kelsoe, John R, Kennedy, James L, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James A, Kranz, Thorsten M, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William B, Leboyer, Marion, Li, Qingqin S, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, and Mayoral, Fermin

Subjects
Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics, Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Humans, Bipolar Disorder, Depressive Disorder, Major, Age of Onset, Multifactorial Inheritance, Genome-Wide Association Study, Autism Spectrum Disorder, Bipolar disorder, GWAS, age at onset, polarity at onset, polygenic score, Genetics, Mental Health, Prevention, Brain Disorders, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Published
2021

8. 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

9. 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

10. Association between polarity of first episode and solar insolation 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, 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., 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, 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, Pfennig, Andrea, Ruiz, Yolanda Pica, 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, Smith, Daniel, Smith, José, Stackhouse, Paul W., Jr., 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
2022
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13. 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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14. 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

17. 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

18. 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

19. Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications

Author

Squassina, Alessio, Manchia, Mirko, Pisanu, Claudia, Ardau, Raffaella, Arzedi, Carlo, Bocchetta, Alberto, Caria, Paola, Cocco, Cristina, Congiu, Donatella, Cossu, Eleonora, Dettori, Tinuccia, Frau, Daniela Virginia, Garzilli, Mario, Manca, Elias, Meloni, Anna, Montis, Maria Antonietta, Mura, Andrea, Nieddu, Mariella, Noli, Barbara, Paribello, Pasquale, Pinna, Federica, Robledo, Renato, Severino, Giovanni, Sogos, Valeria, Del Zompo, Maria, Ferri, Gian Luca, Chillotti, Caterina, Vanni, Roberta, and Carpiniello, Bernardo

Published
2020
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20. 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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21. Prediction of lithium response using genomic data

Author

Stone, William, Nunes, Abraham, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Aubry, Jean-Michel, Backlund, Lena, Bauer, Michael, Bellivier, Frank, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cruceanu, Cristiana, Dayer, Alexandre, Degenhardt, Franziska, Del Zompo, Maria, Forstner, Andreas J., Frye, Mark, Fullerton, Janice M., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hou, Liping, Jiménez, Esther, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kuo, Po-Hsiu, Kusumi, Ichiro, Lavebratt, Catharina, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, McMahon, Francis J., Millischer, Vincent, Mitchell, Philip B., Nöthen, Markus M., O’Donovan, Claire, Ozaki, Norio, Pisanu, Claudia, Reif, Andreas, Rietschel, Marcella, Rouleau, Guy, Rybakowski, Janusz, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Severino, Giovanni, Squassina, Alessio, Veeh, Julia, Vieta, Eduard, Trappenberg, Thomas, and Alda, Martin

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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23. Association between solar insolation and a history of suicide attempts in bipolar I disorder

Author

Bauer, Michael, Glenn, Tasha, Alda, Martin, Andreassen, Ole A., Angelopoulos, Elias, Ardau, Raffaella, Ayhan, Yavuz, Baethge, Christopher, Bauer, Rita, Baune, Bernhard T., Becerra-Palars, Claudia, Bellivier, Frank, Belmaker, Robert H., Berk, Michael, Bersudsky, Yuly, Bicakci, Şule, Birabwa-Oketcho, Harriet, Bjella, Thomas D., Cabrera, Jorge, Wo Cheung, Eric Y., Del Zompo, Maria, Dodd, Seetal, Donix, Markus, Etain, Bruno, Fagiolini, Andrea, Fountoulakis, Kostas N., Frye, Mark A., Gonzalez-Pinto, Ana, Gottlieb, John F., Grof, Paul, Harima, Hirohiko, Henry, Chantal, Isometsä, Erkki T., Janno, Sven, Kapczinski, Flávio, Kardell, Mathias, Khaldi, Slim, Kliwicki, Sebastian, König, Barbara, Kot, Timur L., Krogh, Rikke, Kunz, Mauricio, Lafer, Beny, Landén, Mikael, Larsen, Erik R., Lewitzka, Ute, Licht, Rasmus W., Lopez-Jaramillo, Carlos, MacQueen, Glenda, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Mónica, Melle, Ingrid, Meza-Urzúa, Fátima, Ming, Mok Yee, Monteith, Scott, Morken, Gunnar, Mosca, Enrica, Mozzhegorov, Anton A., Munoz, Rodrigo, Mythri, Starlin V., Nacef, Fethi, Nadella, Ravi K., Nery, Fabiano G., Nielsen, René E., O'Donovan, Claire, Omrani, Adel, Osher, Yamima, Sørensen, Helle Østermark, Ouali, Uta, Ruiz, Yolanda Pica, Pilhatsch, Maximilian, Pinna, Marco, da Ponte, Francisco D.R., Quiroz, Danilo, Ramesar, Raj, Rasgon, Natalie, Reddy, M.S., Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Raghuraman, Bharathram Sathur, Scippa, Ângela M., Severus, Emanuel, Simhandl, Christian, Stackhouse, Paul W., Jr., Stein, Dan J., Strejilevich, Sergio, Subramaniam, Mythily, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Tagata, Hiromi, Tatebayashi, Yoshitaka, Tondo, Leonardo, Torrent, Carla, Vaaler, Arne E., Vares, Edgar, Veeh, Julia, Vieta, Eduard, Viswanath, Biju, Yoldi-Negrete, Maria, Zetin, Mark, Zgueb, Yosra, and Whybrow, Peter C.

Published
2019
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24. Exemplar scoring identifies genetically separable phenotypes of lithium responsive bipolar disorder

Author

Nunes, Abraham, Stone, William, Ardau, Raffaella, Berghöfer, Anne, Bocchetta, Alberto, Chillotti, Caterina, Deiana, Valeria, Degenhardt, Franziska, Forstner, Andreas J., Garnham, Julie S., Grof, Eva, Hajek, Tomas, Manchia, Mirko, Mattheisen, Manuel, McMahon, Francis, Müller-Oerlinghausen, Bruno, Nöthen, Markus M., Pinna, Marco, Pisanu, Claudia, O’Donovan, Claire, Rietschel, Marcella D. C., Rouleau, Guy, Schulze, Thomas, Severino, Giovanni, Slaney, Claire M., Squassina, Alessio, Suwalska, Aleksandra, Turecki, Gustavo, Uher, Rudolf, Zvolsky, Petr, Cervantes, Pablo, del Zompo, Maria, Grof, Paul, Rybakowski, Janusz, Tondo, Leonardo, Trappenberg, Thomas, and Alda, Martin

Published
2021
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25. Lower Plasma Levels of Selective VGF (Non-Acronymic) Peptides in Bipolar Disorder: Comparative Analysis Reveals Distinct Patterns across Mood Disorders and Healthy Controls.

Author

Cocco, Cristina, Noli, Barbara, Manconi, Barbara, Contini, Cristina, Manca, Elias, Pisanu, Claudia, Meloni, Anna, Manchia, Mirko, Paribello, Pasquale, Chillotti, Caterina, Ardau, Raffaella, Severino, Giovanni, and Squassina, Alessio

Subjects
NERVE growth factor, MENTAL depression, AFFECTIVE disorders, BIPOLAR disorder, PROTEIN precursors
Abstract

Introduction: Discriminating bipolar disorder (BD) from major depressive disorder (MDD) remains a challenging clinical task. Identifying specific peripheral biosignatures that can differentiate between BD and MDD would significantly increase diagnostic accuracy. Dysregulated neuroplasticity is implicated in BD and MDD, and psychotropic medications restore specific disrupted processes by increasing neurotrophic signalling. The nerve growth factor inducible vgf gene (non-acronymic) encodes a precursor protein named proVGF, which undergoes proteolytic processing to produce several VGF peptides, some of which were suggested to be implicated in mood disorders and have antidepressant effects. Since the presence of VGF peptides in humans has been exclusively investigated in brain and cerebrospinal fluid, we aimed to identify which VGF peptides are present in the plasma and to investigate whether their levels could differentiate BD from MDD as well as responders from non-responders to pharmacological interventions. Methods: VGF peptides were investigated in plasma from patients diagnosed with MDD (n = 37) or BD (n = 40 under lithium plus n = 29 never exposed to lithium), as well as healthy controls (HC; n = 36). Results: Three VGF peptides (TLQP-11, AQEE-14, and NAPP-19) were identified using spectrometry analysis of plasma from HC. These peptides were then measured in the entire sample using ELISA, which showed significantly lower levels of AQEE and NAPP in BD than in HC and MDD (p = 5.0 × 10−5, p = 0.001, respectively). Conclusion: Our findings suggest that lower plasma levels of NAPP and AQEE are specifically associated with BD, thus possibly representing a diagnostic biomarker in mood disorders. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.

Author

Herrera-Rivero, Marisol, Gutiérrez-Fragoso, Karina, Thalamuthu, Anbupalam, Amare, Azmeraw T., Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, 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, and Chen, Hsi-Chung

Published
2024
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27. 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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28. 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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29. Internet use by patients with bipolar disorder: Results from an international multisite survey

Author

Bauer, Rita, Conell, Jörn, Glenn, Tasha, Alda, Martin, Ardau, Raffaella, Baune, Bernhard T., Berk, Michael, Bersudsky, Yuly, Bilderbeck, Amy, Bocchetta, Alberto, Bossini, Letizia, Castro, Angela M. Paredes, Cheung, Eric YW., Chillotti, Caterina, Choppin, Sabine, Del Zompo, Maria, Dias, Rodrigo, Dodd, Seetal, Duffy, Anne, Etain, Bruno, Fagiolini, Andrea, Hernandez, Miryam Fernández, Garnham, Julie, Geddes, John, Gildebro, Jonas, Gonzalez-Pinto, Ana, Goodwin, Guy M., Grof, Paul, Harima, Hirohiko, Hassel, Stefanie, Henry, Chantal, Hidalgo-Mazzei, Diego, Kapur, Vaisnvy, Kunigiri, Girish, Lafer, Beny, Larsen, Erik R., Lewitzka, Ute, Licht, Rasmus W., Lund, Anne Hvenegaard, Misiak, Blazej, Monteith, Scott, Munoz, Rodrigo, Nakanotani, Takako, Nielsen, René E, O’Donovan, Claire, Okamura, Yasushi, Osher, Yamima, Piotrowski, Patryk, Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Sawchuk, Brett, Schwartz, Elon, Scippa, Ângela M., Slaney, Claire, Sulaiman, Ahmad H., Suominen, Kirsi, Suwalska, Aleksandra, Tam, Peter, Tatebayashi, Yoshitaka, Tondo, Leonardo, Vieta, Eduard, Vinberg, Maj, Viswanath, Biju, Volkert, Julia, Zetin, Mark, Whybrow, Peter C., and Bauer, Michael

Published
2016
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30. 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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31. Influence of light exposure during early life on the age of onset of bipolar disorder

Author

Bauer, Michael, Glenn, Tasha, Alda, Martin, Andreassen, Ole A., Angelopoulos, Elias, Ardau, Raffaella, Baethge, Christopher, Bauer, Rita, Baune, Bernhard T., Bellivier, Frank, Belmaker, Robert H., Berk, Michael, Bjella, Thomas D., Bossini, Letizia, Bersudsky, Yuly, Wo Cheung, Eric Yat, Conell, Jörn, Del Zompo, Maria, Dodd, Seetal, Etain, Bruno, Fagiolini, Andrea, Frye, Mark A., Fountoulakis, Kostas N., Garneau-Fournier, Jade, Gonzalez-Pinto, Ana, Gottlieb, John F., Harima, Hirohiko, Hassel, Stefanie, Henry, Chantal, Iacovides, Apostolos, Isometsä, Erkki T., Kapczinski, Flávio, Kliwicki, Sebastian, König, Barbara, Krogh, Rikke, Kunz, Mauricio, Lafer, Beny, Larsen, Erik R., Lewitzka, Ute, Lopez-Jaramillo, Carlos, MacQueen, Glenda, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Mónica, Melle, Ingrid, Monteith, Scott, Morken, Gunnar, Munoz, Rodrigo, Nery, Fabiano G., O'Donovan, Claire, Osher, Yamima, Pfennig, Andrea, Quiroz, Danilo, Ramesar, Raj, Rasgon, Natalie, Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Miranda- Scippa, Ângela, Severus, Emanuel, Simhandl, Christian, Stein, Dan J., Strejilevich, Sergio, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Tagata, Hiromi, Tatebayashi, Yoshitaka, Torrent, Carla, Vieta, Eduard, Viswanath, Biju, Wanchoo, Mihir J., Zetin, Mark, and Whybrow, Peter C.

Published
2015
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33. Online information seeking by patients with bipolar disorder: results from an international multisite survey

Author

Conell, Jörn, Bauer, Rita, Glenn, Tasha, Alda, Martin, Ardau, Raffaella, Baune, Bernhard T., Berk, Michael, Bersudsky, Yuly, Bilderbeck, Amy, Bocchetta, Alberto, Bossini, Letizia, Paredes Castro, Angela Marianne, Cheung, Eric Yat Wo, Chillotti, Caterina, Choppin, Sabine, Del Zompo, Maria, Dias, Rodrigo, Dodd, Seetal, Duffy, Anne, Etain, Bruno, Fagiolini, Andrea, Garnham, Julie, Geddes, John, Gildebro, Jonas, Gonzalez-Pinto, Ana, Goodwin, Guy M., Grof, Paul, Harima, Hirohiko, Hassel, Stefanie, Henry, Chantal, Hidalgo-Mazzei, Diego, Kapur, Vaisnvy, Kunigiri, Girish, Lafer, Beny, Lam, Chun, Larsen, Erik Roj, Lewitzka, Ute, Licht, Rasmus, Lund, Anne Hvenegaard, Misiak, Blazej, Piotrowski, Patryk, Monteith, Scott, Munoz, Rodrigo, Nakanotani, Takako, Nielsen, René E., O’Donovan, Claire, Okamura, Yasushi, Osher, Yamima, Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Sawchuk, Brett, Schwartz, Elon, Scippa, Ângela Miranda, Slaney, Claire, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Suwalska, Aleksandra, Tam, Peter, Tatebayashi, Yoshitaka, Tondo, Leonardo, Vieta, Eduard, Vinberg, Maj, Viswanath, Biju, Volkert, Julia, Zetin, Mark, Zorrilla, Iñaki, Whybrow, Peter C., and Bauer, Michael

Published
2016
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34. Relationship between sunlight and the age of onset of bipolar disorder: An international multisite study

Author

Bauer, Michael, Glenn, Tasha, Alda, Martin, Andreassen, Ole A., Angelopoulos, Elias, Ardau, Raffaella, Baethge, Christopher, Bauer, Rita, Bellivier, Frank, Belmaker, Robert H., Berk, Michael, Bjella, Thomas D., Bossini, Letizia, Bersudsky, Yuly, Cheung, Eric Yat Wo, Conell, Jörn, Zompo, Maria Del, Dodd, Seetal, Etain, Bruno, Fagiolini, Andrea, Frye, Mark A., Fountoulakis, Kostas N., Garneau-Fournier, Jade, González-Pinto, Ana, Harima, Hirohiko, Hassel, Stefanie, Henry, Chantal, Iacovides, Apostolos, Isometsä, Erkki T., Kapczinski, Flávio, Kliwicki, Sebastian, König, Barbara, Krogh, Rikke, Kunz, Mauricio, Lafer, Beny, Larsen, Erik R., Lewitzka, Ute, Lopez-Jaramillo, Carlos, MacQueen, Glenda, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Mónica, Melle, Ingrid, Monteith, Scott, Morken, Gunnar, Munoz, Rodrigo, Nery, Fabiano G., O’Donovan, Claire, Osher, Yamima, Pfennig, Andrea, Quiroz, Danilo, Ramesar, Raj, Rasgon, Natalie, Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Scippa, Ângela M., Severus, Emanuel, Simhandl, Christian, Stein, Dan J., Strejilevich, Sergio, Hatim Sulaiman, Ahmad, Suominen, Kirsi, Tagata, Hiromi, Tatebayashi, Yoshitaka, Torrent, Carla, Vieta, Eduard, Viswanath, Biju, Wanchoo, Mihir J., Zetin, Mark, and Whybrow, Peter C.

Published
2014
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35. 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

36. Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study

Author

Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, 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, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, 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., Tortorella, Alfonso, 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, Pfennig, Andrea, Potash, James B., Reif, Andreas, Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, Rietschel, Marcella, McMahon, Francis J., Schulze, Thomas G., and Baune, Bernhard T.

Published
2018
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37. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Author

Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jiménez, Esther, Kahn, Jean Pierre, Kassem, Layla, Kuo, Po Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andreas, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas H.R., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane varregaard, Clarke, Toni Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Hickie, Ian B., Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Dannlowski, Udo, de Geus, E. J.C., Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., 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, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, McMahon, Francis J., APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Jamain, Stéphane, University of Adelaide, South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Mental Health Services [Adelaide, SA, Australia], National Institute of Mental Health (NIMH), Ludwig Maximilian University [Munich] (LMU), Georg-August-University = Georg-August-Universität Göttingen, Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard Medical School [Boston] (HMS), Harvard School of Public Health, University of California [San Diego] (UC San Diego), University of California (UC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain] (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Geneva University Hospital (HUG), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], 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), Karl-Franzens-Universität Graz, Mayo Clinic [Rochester], McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University Hospital Basel [Basel], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), 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), Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Basel (Unibas), Neuroscience Research Australia [Sydney, NSW, Australia] (NRA), University of New South Wales [Sydney] (UNSW), Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux], SECOP - centre hospitalier Charles Perrens, 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], Graduate School of Medicine [Osaka], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy (CPN), National Institutes of Health [Bethesda] (NIH), Environmental Molecular Biology Laboratory (RIKEN), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Goethe-University Frankfurt am Main, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University Graduate School of Medicine [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], Research Service VA San Diego Healthcare System, Università degli Studi di Perugia = University of Perugia (UNIPG), University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, University of Salerno (UNISA), University of the Study of Campania Luigi Vanvitelli, National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University Graduate School of Medicine [Japon], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Medical University Graz, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Sigmund Freud University (SFU), Douglas Mental Health University Institute [Montréal], University of Heidelberg, Medical Faculty, Black Dog Institute [Sydney, Australia], Johns Hopkins Bloomberg School of Public Health [Baltimore], 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, The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie], University of Melbourne, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium: Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Varregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan., Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Georg-August-University [Göttingen], University of California, Universita degli Studi di Cagliari [Cagliari], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Graz, Università degli Studi di Perugia (UNIPG), University of Münster, Karl-Franzens-Universität [Graz, Autriche], Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Cearns, M., Heilbronner, U., Degenhardt, F., Tekola-Ayele, F., Hsu, Y. -H., Shekhtman, T., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Brichant-Petitjean, C., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Del Zompo, M., Depaulo, J. R., Etain, B., Jamain, S., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Herms, S., Hoffmann, P., Hofmann, A., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J. R., Kittel-Schneider, S., Kliwicki, S., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Tortorella, A., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S. L., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Pfennig, A., Potash, J. B., Reif, A., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bigdeli, T. B., Binder, E. B., Blackwood, D. H. R., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J., Clarke, T. -K., Coleman, J. R. I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G. E., Davies, G., Deary, I. J., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Kiadeh, F. F. H., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Gordon, S. D., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Krogh, J., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Mcgrath, P., Mcguffin, P., Medland, S. E., Mehta, D., Middeldorp, C. M., Mihailov, E., Milaneschi, Y., Milani, L., Montgomery, G. W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Owen, M. J., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Pettersson, E., Peyrot, W. J., Pistis, G., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Rivera, M., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Shi, J., Shyn, S. I., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., Van der Auwera, S., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Witt, S. H., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Baune, B. T., Berger, K., Boomsma, D. I., Dannlowski, U., de Geus, E. J. C., Domenici, E., Domschke, K., Esko, T., Grabe, H. J., Hamilton, S. P., Hayward, C., Heath, A. C., Kendler, K. S., Kloiber, S., Lewis, G., Li, Q. S., Lucae, S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Mortensen, P. B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M. C., Paciga, S. A., Pedersen, N. L., Penninx, B. W. J. H., Perlis, R. H., Porteous, D. J., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T. G., Smoller, J. W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M. M., Werge, T., Lewis, C. M., Levinson, D. F., Breen, G., Borglum, A. D., Sullivan, P. F., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Maj, M., Turecki, G., Vieta, E., Veeh, J., Wright, A., Zandi, P. P., Mitchell, P. B., Bauer, M., Alda, M., Mcmahon, F. J., and Adult Psychiatry

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Lithium (medication), [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, Logistic regression, THERAPY, ddc:616.89, 0302 clinical medicine, Medicine, Major depression, PREDICTORS, Depression (differential diagnoses), RISK, Depression, Psychiatry and Mental health, Quartile, Cohort, AUGMENTATION, medicine.drug, POLARITY, medicine.medical_specialty, GENETICS, Bipolar disorder, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Lithium, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Internal medicine, Humans, ddc:610, AGENTS, Molecular Biology, Genetic association, Depressive Disorder, Major, business.industry, medicine.disease, EFFICACY, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, PHARMACOLOGICAL-TREATMENTS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

© 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Published
2021

38. Internet use by older adults with bipolar disorder: international survey results

Author

Bauer, Rita, Glenn, Tasha, Strejilevich, Sergio, Conell, Jörn, Alda, Martin, Ardau, Raffaella, Baune, Bernhard T., Berk, Michael, Bersudsky, Yuly, Bilderbeck, Amy, Bocchetta, Alberto, Castro, Angela M. Paredes, Cheung, Eric Y. W., Chillotti, Caterina, Choppin, Sabine, Cuomo, Alessandro, Del Zompo, Maria, Dias, Rodrigo, Dodd, Seetal, Duffy, Anne, Etain, Bruno, Fagiolini, Andrea, Fernández Hernandez, Miryam, Garnham, Julie, Geddes, John, Gildebro, Jonas, Gitlin, Michael J., Gonzalez-Pinto, Ana, Goodwin, Guy M., Grof, Paul, Harima, Hirohiko, Hassel, Stefanie, Henry, Chantal, Hidalgo-Mazzei, Diego, Lund, Anne Hvenegaard, Kapur, Vaisnvy, Kunigiri, Girish, Lafer, Beny, Larsen, Erik R., Lewitzka, Ute, Licht, Rasmus W., Misiak, Blazej, Piotrowski, Patryk, Miranda-Scippa, Ângela, Monteith, Scott, Munoz, Rodrigo, Nakanotani, Takako, Nielsen, René E., O’Donovan, Claire, Okamura, Yasushi, Osher, Yamima, Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Sawchuk, Brett, Schwartz, Elon, Slaney, Claire, Sulaiman, Ahmad H., Suominen, Kirsi, Suwalska, Aleksandra, Tam, Peter, Tatebayashi, Yoshitaka, Tondo, Leonardo, Veeh, Julia, Vieta, Eduard, Vinberg, Maj, Viswanath, Biju, Zetin, Mark, Whybrow, Peter C., and Bauer, Michael

Published
2018
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43. Erratum to: Online information seeking by patients with bipolar disorder: results from an international multisite survey

Author

Conell, Jörn, Bauer, Rita, Glenn, Tasha, Alda, Martin, Ardau, Raffaella, Baune, Bernhard T., Berk, Michael, Bersudsky, Yuly, Bilderbeck, Amy, Bocchetta, Alberto, Bossini, Letizia, Paredes Castro, Angela Marianne, Cheung, Eric Yat Wo, Chillotti, Caterina, Choppin, Sabine, Del Zompo, Maria, Dias, Rodrigo, Dodd, Seetal, Duffy, Anne, Etain, Bruno, Fagiolini, Andrea, Garnham, Julie, Geddes, John, Gildebro, Jonas, Gonzalez-Pinto, Ana, Goodwin, Guy M., Grof, Paul, Harima, Hirohiko, Hassel, Stefanie, Henry, Chantal, Hidalgo-Mazzei, Diego, Kapur, Vaisnvy, Kunigiri, Girish, Lafer, Beny, Lam, Chun, Larsen, Erik Roj, Lewitzka, Ute, Licht, Rasmus W., Lund, Anne Hvenegaard, Misiak, Blazej, Piotrowski, Patryk, Monteith, Scott, Munoz, Rodrigo, Nakanotani, Takako, Nielsen, René E., O’Donovan, Claire, Okamura, Yasushi, Osher, Yamima, Reif, Andreas, Ritter, Philipp, Rybakowski, Janusz K., Sagduyu, Kemal, Sawchuk, Brett, Schwartz, Elon, Scippa, Ângela Miranda, Slaney, Claire, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Suwalska, Aleksandra, Tam, Peter, Tatebayashi, Yoshitaka, Tondo, Leonardo, Vieta, Eduard, Vinberg, Maj, Viswanath, Biju, Volkert, Julia, Zetin, Mark, Zorrilla, Iñaki, Whybrow, Peter C., and Bauer, Michael

Published
2017
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44. Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy

Author

Pisanu, Claudia, primary, Vitali, Erika, additional, Meloni, Anna, additional, Congiu, Donatella, additional, Severino, Giovanni, additional, Ardau, Raffaella, additional, Chillotti, Caterina, additional, Trabucchi, Luigi, additional, Bortolomasi, Marco, additional, Gennarelli, Massimo, additional, Minelli, Alessandra, additional, and Squassina, Alessio, additional

Published
2021
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46. Association of ADHD and depression polygenic scores with lithium response: A Consortium for Lithium Genetics study

Author

Coombes, Brandon J, Millischer, Vincent, Amare, Azmeraw T, Vieta, Eduard, Witt, Stephanie H, Zandi, Peter P, Fullerton, Janice M, Alda, Martin, Frye, Mark A, Schulze, Thomas G, McMahon, Francis J, Biernacka, Joanna M, Ardau, Raffaella, Arias, Barbara, Aubry, Jean-Michel, Backlund, Lena, Bauer, Michael, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Batzler, Anthony, Bhattacharjee, Abesh Kumar, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Larrabee, Beth, Degenhardt, Franziska, Zompo, Maria Del, DePaulo, J Raymond, Étain, Bruno, Falkai, Peter, Ferensztajn-Rochowiak, Ewa, Forstner, Andreas J, Frisen, Louise, Gard, Sébastien, Garnham, Julie S, Hou, Liping, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Papiol, Sergi, Kassem, Layla, Kato, Tadafumi, Kelsoe, John R, Kittel-Schneider, Sarah, König, Barbara, Kuo, Po-Hsiu, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Heilbronner, Urs, 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, Adli, Mazda, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Tomas, O'Donovan, Claire, Osby, Urban, Ozaki, Norio, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Akiyama, Kazufumi, 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, Akula, Nirmala, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tortorella, Alfonso, and Turecki, Gustavo

Subjects
ddc:150
Published
2021

47. Characterisation of age and polarity at onset in bipolar disorder

Author

Kalman, Janos, Olde Loohuis, Loes, Vreeker, Annabel, Mcquillin, Andrew, Stahl, Eli, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie, Anderson-Schmidt, Heike, Andreassen, Ole, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade, Boks, Marco, Bromet, Evelyn, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott, Comes, Ashley, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David, Croarkin, Paul, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, del Zompo, Maria, Depaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas, Frye, Mark, Fullerton, Janice, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene, Kelsoe, John, Kennedy, James, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James, Kranz, Thorsten, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William, Leboyer, Marion, Li, Qingqin, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, Mayoral, Fermin, Mcelroy, Susan, Mcinnis, Melvin, McIntosh, Andrew, Medeiros, Helena, Melle, Ingrid, Milanova, Vihra, Mitchell, Philip, Monteleone, Palmiero, Monteleone, Alessio Maria, Nöthen, Markus, Novak, Tomas, Nurnberger, John, O'Brien, Niamh, O'Connell, Kevin, O'Donovan, Claire, O'Donovan, Michael, Opel, Nils, Ortiz, Abigail, Owen, Michael, Pålsson, Erik, Pato, Carlos, Pato, Michele, Pawlak, Joanna, Pfarr, Julia-Katharina, Pisanu, Claudia, Potash, James, Rapaport, Mark, Reich-Erkelenz, Daniela, Reif, Andreas, Reininghaus, Eva, Repple, Jonathan, Richard-Lepouriel, Hélène, Rietschel, Marcella, Ringwald, Kai, Roberts, Gloria, Rouleau, Guy, Schaupp, Sabrina, Scheftner, William, Schmitt, Simon, Schofield, Peter, Schubert, K Oliver, Schulte, Eva, Schweizer, Barbara, Senner, Fanny, Severino, Giovanni, Sharp, Sally, Slaney, Claire, Smeland, Olav, Sobell, Janet, Squassina, Alessio, Stopkova, Pavla, Strauss, John, Tortorella, Alfonso, Turecki, Gustavo, Twarowska-Hauser, Joanna, Veldic, Marin, Vieta, Eduard, Vincent, John, Xu, Wei, Zai, Clement, Zandi, Peter, Di Florio, Arianna, Smoller, Jordan, Biernacka, Joanna, Mcmahon, Francis, Alda, Martin, Müller-Myhsok, Bertram, Koutsouleris, Nikolaos, Falkai, Peter, Freimer, Nelson, Andlauer, Till, Schulze, Thomas, Ophoff, Roel, Depaulo, J. Raymond, Schubert, K. Oliver, Andlauer, Till F.M., Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etain, Bruno, Child and Adolescent Psychiatry / Psychology, Psychiatry, Kalman, J. L., Loohuis, L. M. O., Vreeker, A., Mcquillin, A., Stahl, E. A., Ruderfer, D., Grigoroiu-Serbanescu, M., Panagiotaropoulou, G., Ripke, S., Bigdeli, T. B., Stein, F., Meller, T., Meinert, S., Pelin, H., Streit, F., Papiol, S., Adams, M. J., Adolfsson, R., Adorjan, K., Agartz, I., Aminoff, S. R., Anderson-Schmidt, H., Andreassen, O. A., Ardau, R., Aubry, J. -M., Balaban, C., Bass, N., Baune, B. T., Bellivier, F., Benabarre, A., Bengesser, S., Berrettini, W. H., Boks, M. P., Bromet, E. J., Brosch, K., Budde, M., Byerley, W., Cervantes, P., Chillotti, C., Cichon, S., Clark, S. R., Comes, A. L., Corvin, A., Coryell, W., Craddock, N., Craig, D. W., Croarkin, P. E., Cruceanu, C., Czerski, P. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Djurovic, S., Edenberg, H. J., Al Eissa, M., Elvsashagen, T., Etain, B., Fanous, A. H., Fellendorf, F., Fiorentino, A., Forstner, A. J., Frye, M. A., Fullerton, J. M., Gade, K., Garnham, J., Gershon, E., Gill, M., Goes, F. S., Gordon-Smith, K., Grof, P., Guzman-Parra, J., Hahn, T., Hasler, R., Heilbronner, M., Heilbronner, U., Jamain, S., Jimenez, E., Jones, I., Jones, L., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kennedy, J. L., Kircher, T., Kirov, G., Kittel-Schneider, S., Klohn-Saghatolislam, F., Knowles, J. A., Kranz, T. M., Lagerberg, T. V., Landen, M., Lawson, W. B., Leboyer, M., Li, Q. S., Maj, M., Malaspina, D., Manchia, M., Mayoral, F., Mcelroy, S. L., Mcinnis, M. G., Mcintosh, A. M., Medeiros, H., Melle, I., Milanova, V., Mitchell, P. B., Monteleone, P., Monteleone, A. M., Nothen, M. M., Novak, T., Nurnberger, J. I., O'Brien, N., O'Connell, K. S., O'Donovan, C., O'Donovan, M. C., Opel, N., Ortiz, A., Owen, M. J., Palsson, E., Pato, C., Pato, M. T., Pawlak, J., Pfarr, J. -K., Pisanu, C., Potash, J. B., Rapaport, M. H., Reich-Erkelenz, D., Reif, A., Reininghaus, E., Repple, J., Richard-Lepouriel, H., Rietschel, M., Ringwald, K., Roberts, G., Rouleau, G., Schaupp, S., Scheftner, W. A., Schmitt, S., Schofield, P. R., Schubert, K. O., Schulte, E. C., Schweizer, B., Senner, F., Severino, G., Sharp, S., Slaney, C., Smeland, O. B., Sobell, J. L., Squassina, A., Stopkova, P., Strauss, J., Tortorella, A., Turecki, G., Twarowska-Hauser, J., Veldic, M., Vieta, E., Vincent, J. B., Xu, W., Zai, C. C., Zandi, P. P., Di Florio, A., Smoller, J. W., Biernacka, J. M., Mcmahon, F. J., Alda, M., Muller-Myhsok, B., Koutsouleris, N., Falkai, P., Freimer, N. B., Andlauer, T. F. M., Schulze, T. G., and Ophoff, R. A.

Subjects
Paper, Multifactorial Inheritance, medicine.medical_specialty, Autism Spectrum Disorder, Bipolar disorder, MESH: Age of Onset, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, GWAS, age at onset, polarity at onset, polygenic score, MESH: Depressive Disorder, Major, BF, Genome-wide association study, Disease, Psykiatri, SDG 3 - Good Health and Well-being, ddc:150, Polarity at onset, Internal medicine, MESH: Bipolar Disorder, Polygenic score, medicine, Humans, Academic Psychiatry, Age of Onset, Genetic association, Psychiatry, MESH: Autism Spectrum Disorder, Depressive Disorder, Major, MESH: Humans, business.industry, Age at onset, Heritability, medicine.disease, Genetic architecture, ddc, Psychiatry and Mental health, Schizophrenia, Autism spectrum disorder, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, RC0321, MESH: Multifactorial Inheritance, business, Genome-Wide Association Study
Abstract

BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Published
2021

48. Involvement of microRNAs in Lithium Response in Patients With Bipolar Disorder and Related Phenotypes

Author

Pisanu, Claudia, primary, Congiu, Donatella, additional, Severino, Giovanni, additional, Niola, Paola, additional, Lopez, Juan Pablo, additional, Cruceanu, Cristiana, additional, Ardau, Raffaella, additional, Papadima, Eleni Merkouri, additional, Loizedda, Annalisa, additional, Orrù, Nicola, additional, Calza, Stefano, additional, Orrù, Sandro, additional, Carcassi, Carlo, additional, Alda, Martin, additional, Chillotti, Caterina, additional, Turecki, Gustavo, additional, Del Zompo, Maria, additional, and Squassina, Alessio, additional

Published
2021
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