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2. Neurobiology of Mood Disorders

Author

Manchia, Mirko, Schatzberg, Alan, Schulze, Thomas G., Section editor, Laje, Gonzalo, Section editor, Tasman, Allan, editor, Riba, Michelle B., editor, Alarcón, Renato D., editor, Alfonso, César A., editor, Kanba, Shigenobu, editor, Lecic-Tosevski, Dusica, editor, Ndetei, David M., editor, Ng, Chee H., editor, and Schulze, Thomas G., editor

Published
2024
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4. 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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5. 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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7. Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder

Author

Amare, Azmeraw T., Thalamuthu, Anbupalam, Schubert, Klaus Oliver, Fullerton, Janice M., Ahmed, Muktar, Hartmann, Simon, Papiol, Sergi, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hou, Liping, Hsu, Yi-Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Hasler, Roland, Richard-Lepouriel, Hélène, Perroud, Nader, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Marie-Claire, Cynthia, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Fallgatter, Andreas J., Stegmaier, Sophia, Ethofer, Thomas, Biere, Silvia, Petrova, Kristiyana, Schuster, Ceylan, Adorjan, Kristina, Budde, Monika, Heilbronner, Maria, Kalman, Janos L., Kohshour, Mojtaba Oraki, Reich-Erkelenz, Daniela, Schaupp, Sabrina K., Schulte, Eva C., Senner, Fanny, Vogl, Thomas, Anghelescu, Ion-George, Arolt, Volker, Dannlowski, Udo, Dietrich, Detlef, Figge, Christian, Jäger, Markus, Lang, Fabian U., Juckel, Georg, Konrad, Carsten, Reimer, Jens, Schmauß, Max, Schmitt, Andrea, Spitzer, Carsten, von Hagen, Martin, Wiltfang, Jens, Zimmermann, Jörg, Andlauer, Till F. M., Fischer, Andre, Bermpohl, Felix, Ritter, Philipp, Matura, Silke, Gryaznova, Anna, Falkenberg, Irina, Yildiz, Cüneyt, Kircher, Tilo, Schmidt, Julia, Koch, Marius, Gade, Kathrin, Trost, Sarah, Haussleiter, Ida S., Lambert, Martin, Rohenkohl, Anja C., Kraft, Vivien, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Ferensztajn-Rochowiak, Ewa, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan, Colom, Francesc, Millischer, Vincent, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Pfennig, Andrea, Pisanu, Claudia, Potash, James B., Reif, Andreas, Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, Witt, Stephanie H., Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, Rietschel, Marcella, McMahon, Francis J., Schulze, Thomas G., Clark, Scott R., and Baune, Bernhard T.

Published
2023
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8. Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators

Author

Solmi, Marco, Croatto, Giovanni, Gupta, Arnav, Fabiano, Nicholas, Wong, Stanley, Fornaro, Michele, Schneider, Lynne Kolton, Rohani-Montez, S. Christy, Fairley, Leanne, Smith, Nathalie, Bitter, István, Gorwood, Philip, Taipale, Heidi, Tiihonen, Jari, Cortese, Samuele, Dragioti, Elena, Rietz, Ebba Du, Nielsen, Rene Ernst, Firth, Joseph, Fusar-Poli, Paolo, Hartman, Catharina, Holt, Richard I G, Høye, Anne, Koyanagi, Ai, Larsson, Henrik, Lehto, Kelli, Lindgren, Peter, Manchia, Mirko, Nordentoft, Merete, Skonieczna-Żydecka, Karolina, Stubbs, Brendon, Vancampfort, Davy, De Prisco, Michele, Boyer, Laurent, Vieta, Eduard, and Correll, Christoph U.

Published
2024
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9. Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data

Author

Isayeva, Ulker, Manchia, Mirko, Collu, Roberto, Primavera, Diego, Deriu, Luca, Caboni, Edoardo, Iaselli, Novella Maria, Sundas, Davide, Tusconi, Massimo, Pinna, Federica, Paribello, Pasquale, Scherma, Maria, Pisanu, Claudia, Meloni, Anna, Zai, Clement C., Congiu, Donatella, Squassina, Alessio, Fratta, Walter, Fadda, Paola, and Carpiniello, Bernardo

Published
2024
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10. 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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11. Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia: A systematic review and meta-analysis

Author

Solmi, Marco, Croatto, Giovanni, Fornaro, Michele, Schneider, Lynne Kolton, Rohani-Montez, S. Christy, Fairley, Leanne, Smith, Nathalie, Bitter, István, Gorwood, Philip, Taipale, Heidi, Tiihonen, Jari, Cortese, Samuele, Dragioti, Elena, Rietz, Ebba Du, Nielsen, Rene Ernst, Firth, Joseph, Fusar-Poli, Paolo, Hartman, Catharina, Holt, Richard I G, Høye, Anne, Koyanagi, Ai, Larsson, Henrik, Lehto, Kelli, Lindgren, Peter, Manchia, Mirko, Nordentoft, Merete, Skonieczna-Żydecka, Karolina, Stubbs, Brendon, Vancampfort, Davy, Boyer, Laurent, De Prisco, Michele, Vieta, Eduard, and Correll, Christoph U.

Published
2024
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12. Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders: A systematic review of observational studies

Author

Fabiano, Nicholas, Gupta, Arnav, Wong, Stanley, Tran, Jason, Mohammad, Ibrahim YZ, Bal, Shan, Fiedorowicz, Jess G., Firth, Joseph, Stubbs, Brendon, Vancampfort, Davy, Schuch, Felipe B., Carr, Lucas J., Shorr, Risa, Cortese, Samuele, Manchia, Mirko, Hartman, Catharina A., Høye, Anne, Fusar-Poli, Paolo, Koyanagi, Ai, Vieta, Eduard, Nielsen, René Ernst, Holt, Richard IG, Correll, Christoph U., Du Rietz, Ebba, Taipale, Heidi, Lehto, Kelli, Larrson, Henrik, Nordentoft, Merete, Dragioti, Elena, Skonieczna-Żydecka, Karolina, and Solmi, Marco

Published
2024
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14. 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

16. Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: A translational study

Author

Tassan Mazzocco, Margherita, Pisanu, Claudia, Russo, Luigi, Acconcia, Clementina, Cambiaghi, Marco, De Girolamo, Sofia, Squassina, Alessio, Cherchi, Laura, Monzani, Elena, Scebba, Francesca, Angeloni, Debora, De Gregorio, Danilo, Nasini, Sofia, Dall’Acqua, Stefano, Sut, Stefania, Suprani, Federico, Garzilli, Mario, Guiso, Beatrice, Pulcinelli, Vittoria, Iaselli, Maria Novella, Pinna, Ilaria, Somaini, Giulia, Arru, Laura, Corrias, Carolina, Paribello, Pasquale, Pinna, Federica, Gobbi, Gabriella, Valtorta, Flavia, Carpiniello, Bernardo, Manchia, Mirko, and Comai, Stefano

Published
2023
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17. Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Author

Müderrisoğlu, Ahmet, Privat, Alba Toll, Bouhuis, Alde, Hasan, Alkomiet, Jongkind, Amy, Gonzalez-Pinto, Ana, Santacana, Anna Mane, D'Agostino, Armando, Ertugrul, Aygün, Yağcioğlu, Ayşe Elif Anil, Crespo-Facorro, Benedicto, Sanchez-Barbero, Bianca, Spuch, Carlos, Morgenroth, Carla Lou, de Pinedo, Carmen Fernandez, Casetta, Cecilia, Bousman, Chad, Pantelis, Christos, Ovejas-Catalán, Claudia, Garcia-Rizo, Clemente, Okhuijsen-Pfeifer, Cynthia, Cohen, Dan, Ristic, Dragana Ignjatovic, Beld, Edwin, Repo-Tiihonen, Eila, Wagner, Elias, Jeger-Land, Ellen, Vilella, Elisabet, Bekema, Erwin, Sepúlveda, Stevan, Seghi, Federico, Wiedenmann, Federico, Martini, Francesca, Serio, Francesca, Vairano, Francesca, Mercuriali, Giacomo, Boido, Giovanni, Yoca, Gökhan, van Beek, Hanneke, Gijsman, Harm, Tuppurainen, Heli, Everall, Ian, Novakovic, Ivona, Zorrilla, Inaki, Erdoğan, Ibrahim Mert, Sapienza, Jacopo, Bogers, Jan, Tiihonen, Jari, Vázquez-Bourgon, Javier, van Os, Jim, Schneider-Thoma, Johannes, Luykx, Jurjen, Grootens, Koen, Mar-Barrutia, Lorea, Martorell, Lourdes, Bak, Maarten, Spangaro, Marco, de Vos, Marije, de Koning, Mariken, Garriga, Marina, Lähteenvuo, Markku, Bosia, Marta, van der Horst, Marte, Babaoğlu, Melih Önder, Veereschild, Mike, Manchia, Mirko, Edlinger, Monika, Fuentes-Pérez, Paloma, Paribello, Pasquale, Lopez-Pena, Purificacion, Kahn, René, Cavallaro, Roberto, Veerman, Selene, Gutwinski, Stefan, Schreiter, Stefanie, Ripke, Stephan, Baltanás, Tania Rivera, Oviedo-Salcedo, Tatiana, Hallikainen, Tero, Görlitz, Thomas, Alink, Wouter, Ayhan, Yavuz, van der Horst, Marte Z., Meijer, Yoeki, de Boer, Nini, Guloksuz, Sinan, Siskind, Dan, and Luykx, Jurjen J.

Published
2023
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18. 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

19. 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

23. Overview of CAPICE—Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe—an EU Marie Skłodowska-Curie International Training Network

Author

Rajula, Hema Sekhar Reddy, Manchia, Mirko, Agarwal, Kratika, Akingbuwa, Wonuola A., Allegrini, Andrea G., Diemer, Elizabeth, Doering, Sabrina, Haan, Elis, Jami, Eshim S., Karhunen, Ville, Leone, Marica, Schellhas, Laura, Thompson, Ashley, van den Berg, Stéphanie M., Bergen, Sarah E., Kuja-Halkola, Ralf, Hammerschlag, Anke R., Järvelin, Marjo Riitta, Leval, Amy, Lichtenstein, Paul, Lundstrom, Sebastian, Mauri, Matteo, Munafò, Marcus R., Myers, David, Plomin, Robert, Rimfeld, Kaili, Tiemeier, Henning, Ystrom, Eivind, Fanos, Vassilios, Bartels, Meike, and Middeldorp, Christel M.

Published
2022
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24. Ethical considerations for precision psychiatry: A roadmap for research and clinical practice

Author

Fusar-Poli, Paolo, Manchia, Mirko, Koutsouleris, Nikolaos, Leslie, David, Woopen, Christiane, Calkins, Monica E., Dunn, Michael, Tourneau, Christophe Le, Mannikko, Miia, Mollema, Tineke, Oliver, Dominic, Rietschel, Marcella, Reininghaus, Eva Z., Squassina, Alessio, Valmaggia, Lucia, Kessing, Lars Vedel, Vieta, Eduard, Correll, Christoph U., Arango, Celso, and Andreassen, Ole A.

Published
2022
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25. 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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26. 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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27. Lithium induced hypercalcemia: an expert opinion and management algorithm

Author

Kovacs, Zoltan, Vestergaard, Peter, W. Licht, Rasmus, P. V. Straszek, Sune, Hansen, Anne Sofie, H. Young, Allan, Duffy, Anne, Müller-Oerlinghausen, Bruno, Seemueller, Florian, Sani, Gabriele, Rubakowski, Janusz, Priller, Josef, Vedel Kessing, Lars, Tondo, Leonardo, Alda, Martin, Manchia, Mirko, Grof, Paul, Ritter, Phillip, Hajek, Tomas, Lewitzka, Ute, Bergink, Veerle, Bauer, Michael, and Nielsen, René Ernst

Published
2022
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31. Outcomes associated with different vaccines in individuals with bipolar disorder and impact on the current COVID-19 pandemic- a systematic review

Author

Reininghaus, Eva Z, Manchia, Mirko, Dalkner, Nina, Bonkat, Nina, Squassina, Alessio, Hodl, Isabel, Vieta, Eduard, Reif, Andreas, Hajek, Tomas, Landén, Mikael, Correll, Christoph U, Scott, Jan, Etain, Bruno, Rietschel, Marcella, Bergink, Veerle, Martinez-Cengotitabengoa, Monica, Kessing, Lars Vedel, Fagiolini, Andrea, Bauer, Michael, Goodwin, Guy, Gonzalez-Pinto, Ana, Kupka, Ralph W, Schulze, Thomas G, Lagerberg, Trine V, Yildiz, Ayşegül, Henry, Chantal, Morken, Gunnar, Ritter, Phillip, Nieslen, René Ernst, Licht, Rasmus W, Bechdolf, Andreas, Andreassen, Ole A, and Fellendorf, Frederike Tabea

Published
2022
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32. Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes.

Author

Scott, Katie, O'Donovan, Claire, Brancati, Giulio Emilio, Cervantes, Pablo, Ardau, Rafaella, Manchia, Mirko, Severino, Giovanni, Rybakowski, Janusz, Tondo, Leonardo, Grof, Paul, Alda, Martin, and Nunes, Abraham

Subjects
LITHIUM carbonate, BIPOLAR disorder, THERAPEUTIC use of lithium, MOOD stabilizers, HIERARCHICAL clustering (Cluster analysis)
Abstract

Introduction: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. Methods: We included adult patients with BD‐I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. Results: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). Conclusions: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples. [ABSTRACT FROM AUTHOR]

Published
2024
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33. A Secondary Analysis of the Complex Interplay between Psychopathology, Cognitive Functions, Brain Derived Neurotrophic Factor Levels, and Suicide in Psychotic Disorders: Data from a 2-Year Longitudinal Study.

Author

Paribello, Pasquale, Manchia, Mirko, Isayeva, Ulker, Upali, Marco, Orrù, Davide, Pinna, Federica, Collu, Roberto, Primavera, Diego, Deriu, Luca, Caboni, Edoardo, Iaselli, Maria Novella, Sundas, Davide, Tusconi, Massimo, Scherma, Maria, Pisanu, Claudia, Meloni, Anna, Zai, Clement C., Congiu, Donatella, Squassina, Alessio, and Fratta, Walter

Subjects
*BRAIN-derived neurotrophic factor, *PSYCHOSES, *PATHOLOGICAL psychology, *NEUROPSYCHOLOGICAL tests, *SECONDARY analysis, *CONVENIENCE sampling (Statistics)
Abstract

Identifying phenotypes at high risk of suicidal behaviour is a relevant objective of clinical and translational research and can facilitate the identification of possible candidate biomarkers. We probed the potential association and eventual stability of neuropsychological profiles and serum BDNF concentrations with lifetime suicide ideation and attempts (LSI and LSA, respectively) in individuals with schizophrenia (SCZ) and schizoaffective disorder (SCA) in a 2-year follow-up study. A secondary analysis was conducted on a convenience sample of previously recruited subjects from a single outpatient clinic. Retrospectively assessed LSI and LSA were recorded by analysing the available longitudinal clinical health records. LSI + LSA subjects consistently exhibited lower PANSS-defined negative symptoms and better performance in the BACS-letter fluency subtask. There was no significant association between BDNF levels and either LSI or LSA. We found a relatively stable pattern of lower negative symptoms over two years among patients with LSI and LSA. No significant difference in serum BDNF concentrations was detected. The translational viability of using neuropsychological profiles as a possible avenue for the identification of populations at risk for suicide behaviours rather than the categorical diagnosis represents a promising option but requires further confirmation. [ABSTRACT FROM AUTHOR]

Published
2024
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34. 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

37. An integrated precision medicine approach in major depressive disorder: a study protocol to create a new algorithm for the prediction of treatment response

Author

Baune, Bernhard T., primary, Minelli, Alessandra, additional, Carpiniello, Bernardo, additional, Contu, Martina, additional, Domínguez Barragán, Jorge, additional, Donlo, Chus, additional, Ferensztajn-Rochowiak, Ewa, additional, Glaser, Rosa, additional, Kelch, Britta, additional, Kobelska, Paulina, additional, Kolasa, Grzegorz, additional, Kopeć, Dobrochna, additional, Martínez de Lagrán Cabredo, María, additional, Martini, Paolo, additional, Mayer, Miguel-Angel, additional, Menesello, Valentina, additional, Paribello, Pasquale, additional, Perera Bel, Júlia, additional, Perusi, Giulia, additional, Pinna, Federica, additional, Pinna, Marco, additional, Pisanu, Claudia, additional, Sierra, Cèsar, additional, Stonner, Inga, additional, Wahner, Viktor T. H., additional, Xicota, Laura, additional, Zang, Johannes C. S., additional, Gennarelli, Massimo, additional, Manchia, Mirko, additional, Squassina, Alessio, additional, Potier, Marie-Claude, additional, Rybakowski, Filip, additional, Sanz, Ferran, additional, and Dierssen, Mara, additional

Published
2024
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39. Neurobiology of Violence

Author

Manchia, Mirko, Booij, Linda, Pinna, Federica, Wong, Janice, Zepf, Florian, Comai, Stefano, Carpiniello, Bernardo, Series Editor, Vita, Antonio, Series Editor, and Mencacci, Claudio, Series Editor

Published
2020
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40. DSM-5 and ICD-11 criteria for bipolar disorder: Implications for the prevalence of bipolar disorder and validity of the diagnosis – A narrative review from the ECNP bipolar disorders network

Author

Kessing, Lars Vedel, González-Pinto, Ana, Fagiolini, Andrea, Bechdolf, Andreas, Reif, Andreas, Yildiz, Ayşegül, Etain, Bruno, Henry, Chantal, Severus, Emanuel, Reininghaus, Eva Z., Morken, Gunnar, Goodwin, Guy M., Scott, Jan, Geddes, John R., Rietschel, Marcella, Landén, Mikael, Manchia, Mirko, Bauer, Michael, Martinez-Cengotitabengoa, Monica, Andreassen, Ole A., Ritter, Philipp, Kupka, Ralph, Licht, Rasmus W., Nielsen, René Ernst, Schulze, Thomas G., Hajek, Tomas, Lagerberg, Trine Vik, Bergink, Veerle, and Vieta, Eduard

Published
2021
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42. The Role of Copper Overload in Modulating Neuropsychiatric Symptoms.

Author

Manchia, Mirko, Paribello, Pasquale, Pinna, Martina, and Faa, Gavino

Subjects
*HEPATOLENTICULAR degeneration, *ALZHEIMER'S disease, *COPPER, *SYMPTOMS, *GENE expression, *MENTAL illness
Abstract

Copper is a transition metal essential for growth and development and indispensable for eukaryotic life. This metal is essential to neuronal function: its deficiency, as well as its overload have been associated with multiple neurodegenerative disorders such as Alzheimer's disease and Wilson's disease and psychiatric conditions such as schizophrenia, bipolar disorder, and major depressive disorders. Copper plays a fundamental role in the development and function of the human Central Nervous System (CNS), being a cofactor of multiple enzymes that play a key role in physiology during development. In this context, we thought it would be timely to summarize data on alterations in the metabolism of copper at the CNS level that might influence the development of neuropsychiatric symptoms. We present a non-systematic review with the study selection based on the authors' judgement to offer the reader a perspective on the most significant elements of neuropsychiatric symptoms in Wilson's disease. We highlight that Wilson's disease is characterized by marked heterogeneity in clinical presentation among patients with the same mutation. This should motivate more research efforts to disentangle the role of environmental factors in modulating the expression of genetic predisposition to this disorder. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Assisted Reproductive Technologies: A New Player in the Foetal Programming of Childhood and Adult Diseases?

Author

Faa, Gavino, Manchia, Mirko, and Fanos, Vassilios

Subjects
*REPRODUCTIVE technology, *JUVENILE diseases, *HUMAN abnormalities, *PERINATAL period, *CONGENITAL disorders, *EMBRYO transfer
Abstract

Assisted reproductive technology (ART) is an emerging field in medicine that incorporates complex procedures and has profound ethical, moral, social, religious, and economic implications not just for the individuals who have access to this method but also for society. In this narrative review, we summarise multiple aspects of ART procedures and the possible consequences on the mother and newborn. Moreover, we provide an overview of the possible long-term consequences of ART procedures on the health of newborns, although longitudinal evidence is particularly scant. Users should be informed that ART procedures are not risk-free to prepare them for the possible negative outcomes that may occur in the perinatal period or even in childhood and adulthood. Indeed, risk estimates point to increased liability for major nonchromosomal birth defects; cardiovascular, musculoskeletal, and urogenital (in male newborns) defects; and any other birth defects. Less certainty is present for the risk of neuropsychiatric sequelae in children conceived through ART. Thus, its application should be accompanied by adequate counselling and psychological support, possibly integrated into specific multidisciplinary clinical programmes. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action

Author

Manchia, Mirko, Vieta, Eduard, Smeland, Olav B., Altimus, Cara, Bechdolf, Andreas, Bellivier, Frank, Bergink, Veerle, Fagiolini, Andrea, Geddes, John R., Hajek, Tomas, Henry, Chantal, Kupka, Ralph, Lagerberg, Trine V., Licht, Rasmus W., Martinez-Cengotitabengoa, Monica, Morken, Gunnar, Nielsen, René E., Pinto, Ana Gonzalez, Reif, Andreas, Rietschel, Marcella, Ritter, Phillip, Schulze, Thomas G., Scott, Jan, Severus, Emanuel, Yildiz, Aysegul, Kessing, Lars Vedel, Bauer, Michael, Goodwin, Guy M., and Andreassen, Ole A.

Published
2020
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46. 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

47. 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

49. Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: a translational study

Author

Mazzocco, Margherita Tassan, primary, Pisanu, Claudia, additional, Russo, Luigi, additional, Acconcia, Clementina, additional, Cambiaghi, Marco, additional, De Girolamo, Sofia, additional, Squassina, Alessio, additional, Cherchi, Laura, additional, Monzani, Elena, additional, Scebba, Francesca, additional, Angeloni, Debora, additional, De Gregorio, Danilo, additional, Nasini, Sofia, additional, Dall’Acqua, Stefano, additional, Sut, Stefania, additional, Suprani, Federico, additional, Garzilli, Mario, additional, Guiso, Beatrice, additional, Pulcinelli, Vittoria, additional, Iaselli, Maria Novella, additional, Pinna, Ilaria, additional, Somaini, Giulia, additional, Arru, Laura, additional, Corrias, Carolina, additional, Paribello, Pasquale, additional, Pinna, Federica, additional, Gobbi, Gabriella, additional, Valtorta, Flavia, additional, Carpiniello, Bernardo, additional, Manchia, Mirko, additional, and Comai, Stefano, additional

Published
2023
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