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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental 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 pe...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Journal Experts
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949170/ https://www.ncbi.nlm.nih.gov/pubmed/36824922 http://dx.doi.org/10.21203/rs.3.rs-2580252/v1 |
| _version_ | 1784892918826270720 |
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| author | Amare, Azmeraw Thalamuthu, Anbupalam Schubert, Klaus Oliver 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 Backlund, Lena Bhattacharjee, Abesh Kumar Bellivier, Frank Benabarre, Antoni 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. Raymond Etain, Bruno Jamain, Stéphane Falkai, Peter Forstner, Andreas J. Frisén, 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 Oraki Kohshour, Mojtaba Reich-Erkelenz, Daniela Schaupp, Sabrina Schulte, Eva Senner, Fanny Vogl, Thomas Anghelescu, Ion-George Arolt, Volker Dannlowski, Udo Dietrich, Detlef E. Figge, Christian Jäger, Markus Lang, Fabian Juckel, Georg Spitzer, Carsten Reimer, Jens Schmauß, Max Schmitt, Andrea Konrad, Carsten von Hagen, Martin Wiltfang, Jens Zimmermann, Jörg Andlauer, Till Fischer, Andre Bermpohl, Felix Kraft, Vivien Matura, Silke Gryaznova, Anna Falkenberg, Irina Yildiz, Cüneyt Kircher, Tilo Schmidt, Julia Koch, Marius Gade, Katrin Trost, Sarah Haußleiter, Ida 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 McElroy, Susan L. Colom, Francesc Mitjans, Marina Mondimore, Francis Monteleone, Palmiero Nievergelt, Caroline Nöthen, Markus Novak, Tomas O’Donovan, Claire Ozaki, Norio Pfennig, Andrea Pisanu, Claudia Potash, James Reif, Andreas Reininghaus, Eva Rouleau, Guy Rybakowski, Janusz K. Schalling, Martin Schofield, Peter Schweizer, Barbara W. Severino, Giovanni Shilling, Paul D Shimoda, Kazutaka Simhandl, Christian Slaney, Claire Squassina, Alessio Stamm, Thomas Stopkova, Pavla Maj, Mario Turecki, Gustavo Vieta, Eduard Veeh, Julia Witt, Stephanie Wright, Adam Zandi, Peter Mitchell, Philip Bauer, Michael Alda, Martin Rietschel, Marcella McMahon, Francis Schulze, Thomas G. Millischer, Vincent Clark, Scott Baune, Bernhard |
| author_facet | Amare, Azmeraw Thalamuthu, Anbupalam Schubert, Klaus Oliver 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 Backlund, Lena Bhattacharjee, Abesh Kumar Bellivier, Frank Benabarre, Antoni 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. Raymond Etain, Bruno Jamain, Stéphane Falkai, Peter Forstner, Andreas J. Frisén, 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 Oraki Kohshour, Mojtaba Reich-Erkelenz, Daniela Schaupp, Sabrina Schulte, Eva Senner, Fanny Vogl, Thomas Anghelescu, Ion-George Arolt, Volker Dannlowski, Udo Dietrich, Detlef E. Figge, Christian Jäger, Markus Lang, Fabian Juckel, Georg Spitzer, Carsten Reimer, Jens Schmauß, Max Schmitt, Andrea Konrad, Carsten von Hagen, Martin Wiltfang, Jens Zimmermann, Jörg Andlauer, Till Fischer, Andre Bermpohl, Felix Kraft, Vivien Matura, Silke Gryaznova, Anna Falkenberg, Irina Yildiz, Cüneyt Kircher, Tilo Schmidt, Julia Koch, Marius Gade, Katrin Trost, Sarah Haußleiter, Ida 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 McElroy, Susan L. Colom, Francesc Mitjans, Marina Mondimore, Francis Monteleone, Palmiero Nievergelt, Caroline Nöthen, Markus Novak, Tomas O’Donovan, Claire Ozaki, Norio Pfennig, Andrea Pisanu, Claudia Potash, James Reif, Andreas Reininghaus, Eva Rouleau, Guy Rybakowski, Janusz K. Schalling, Martin Schofield, Peter Schweizer, Barbara W. Severino, Giovanni Shilling, Paul D Shimoda, Kazutaka Simhandl, Christian Slaney, Claire Squassina, Alessio Stamm, Thomas Stopkova, Pavla Maj, Mario Turecki, Gustavo Vieta, Eduard Veeh, Julia Witt, Stephanie Wright, Adam Zandi, Peter Mitchell, Philip Bauer, Michael Alda, Martin Rietschel, Marcella McMahon, Francis Schulze, Thomas G. Millischer, Vincent Clark, Scott Baune, Bernhard |
| author_sort | Amare, Azmeraw |
| collection | PubMed |
| description | Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental 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 lithium’s 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=2,367) 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 rst four genetic principal components. Statistical significance was determined at P< 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10–12, R2=1.9%) and continuous (P=6.4×10–9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22–5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10–4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment. Keywords: Polygenic score, pharmacogenomics, lithium, bipolar disorder, psychiatry |
| format | Online Article Text |
| id | pubmed-9949170 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | American Journal Experts |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-99491702023-02-24 Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder Amare, Azmeraw Thalamuthu, Anbupalam Schubert, Klaus Oliver 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 Backlund, Lena Bhattacharjee, Abesh Kumar Bellivier, Frank Benabarre, Antoni 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. Raymond Etain, Bruno Jamain, Stéphane Falkai, Peter Forstner, Andreas J. Frisén, 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 Oraki Kohshour, Mojtaba Reich-Erkelenz, Daniela Schaupp, Sabrina Schulte, Eva Senner, Fanny Vogl, Thomas Anghelescu, Ion-George Arolt, Volker Dannlowski, Udo Dietrich, Detlef E. Figge, Christian Jäger, Markus Lang, Fabian Juckel, Georg Spitzer, Carsten Reimer, Jens Schmauß, Max Schmitt, Andrea Konrad, Carsten von Hagen, Martin Wiltfang, Jens Zimmermann, Jörg Andlauer, Till Fischer, Andre Bermpohl, Felix Kraft, Vivien Matura, Silke Gryaznova, Anna Falkenberg, Irina Yildiz, Cüneyt Kircher, Tilo Schmidt, Julia Koch, Marius Gade, Katrin Trost, Sarah Haußleiter, Ida 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 McElroy, Susan L. Colom, Francesc Mitjans, Marina Mondimore, Francis Monteleone, Palmiero Nievergelt, Caroline Nöthen, Markus Novak, Tomas O’Donovan, Claire Ozaki, Norio Pfennig, Andrea Pisanu, Claudia Potash, James Reif, Andreas Reininghaus, Eva Rouleau, Guy Rybakowski, Janusz K. Schalling, Martin Schofield, Peter Schweizer, Barbara W. Severino, Giovanni Shilling, Paul D Shimoda, Kazutaka Simhandl, Christian Slaney, Claire Squassina, Alessio Stamm, Thomas Stopkova, Pavla Maj, Mario Turecki, Gustavo Vieta, Eduard Veeh, Julia Witt, Stephanie Wright, Adam Zandi, Peter Mitchell, Philip Bauer, Michael Alda, Martin Rietschel, Marcella McMahon, Francis Schulze, Thomas G. Millischer, Vincent Clark, Scott Baune, Bernhard Res Sq Article Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental 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 lithium’s 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=2,367) 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 rst four genetic principal components. Statistical significance was determined at P< 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10–12, R2=1.9%) and continuous (P=6.4×10–9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22–5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10–4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment. Keywords: Polygenic score, pharmacogenomics, lithium, bipolar disorder, psychiatry American Journal Experts 2023-02-14 /pmc/articles/PMC9949170/ /pubmed/36824922 http://dx.doi.org/10.21203/rs.3.rs-2580252/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/) |
| spellingShingle | Article Amare, Azmeraw Thalamuthu, Anbupalam Schubert, Klaus Oliver 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 Backlund, Lena Bhattacharjee, Abesh Kumar Bellivier, Frank Benabarre, Antoni 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. Raymond Etain, Bruno Jamain, Stéphane Falkai, Peter Forstner, Andreas J. Frisén, 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 Oraki Kohshour, Mojtaba Reich-Erkelenz, Daniela Schaupp, Sabrina Schulte, Eva Senner, Fanny Vogl, Thomas Anghelescu, Ion-George Arolt, Volker Dannlowski, Udo Dietrich, Detlef E. Figge, Christian Jäger, Markus Lang, Fabian Juckel, Georg Spitzer, Carsten Reimer, Jens Schmauß, Max Schmitt, Andrea Konrad, Carsten von Hagen, Martin Wiltfang, Jens Zimmermann, Jörg Andlauer, Till Fischer, Andre Bermpohl, Felix Kraft, Vivien Matura, Silke Gryaznova, Anna Falkenberg, Irina Yildiz, Cüneyt Kircher, Tilo Schmidt, Julia Koch, Marius Gade, Katrin Trost, Sarah Haußleiter, Ida 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 McElroy, Susan L. Colom, Francesc Mitjans, Marina Mondimore, Francis Monteleone, Palmiero Nievergelt, Caroline Nöthen, Markus Novak, Tomas O’Donovan, Claire Ozaki, Norio Pfennig, Andrea Pisanu, Claudia Potash, James Reif, Andreas Reininghaus, Eva Rouleau, Guy Rybakowski, Janusz K. Schalling, Martin Schofield, Peter Schweizer, Barbara W. Severino, Giovanni Shilling, Paul D Shimoda, Kazutaka Simhandl, Christian Slaney, Claire Squassina, Alessio Stamm, Thomas Stopkova, Pavla Maj, Mario Turecki, Gustavo Vieta, Eduard Veeh, Julia Witt, Stephanie Wright, Adam Zandi, Peter Mitchell, Philip Bauer, Michael Alda, Martin Rietschel, Marcella McMahon, Francis Schulze, Thomas G. Millischer, Vincent Clark, Scott Baune, Bernhard Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder |
| title | Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder |
| title_full | Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder |
| title_fullStr | Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder |
| title_full_unstemmed | Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder |
| title_short | Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder |
| title_sort | association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949170/ https://www.ncbi.nlm.nih.gov/pubmed/36824922 http://dx.doi.org/10.21203/rs.3.rs-2580252/v1 |
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associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT bieresilvia associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT petrovakristiyana associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schusterceylan associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT adorjankristina associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT buddemonika associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT heilbronnermaria associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kalmanjanos associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT orakikohshourmojtaba associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT reicherkelenzdaniela associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schauppsabrina associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schulteeva associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT sennerfanny associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT voglthomas associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT anghelescuiongeorge associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT aroltvolker associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT dannlowskiudo associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT dietrichdetlefe associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT figgechristian associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT jagermarkus associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT langfabian associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT juckelgeorg associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT spitzercarsten associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT reimerjens associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schmaußmax associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schmittandrea associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT konradcarsten associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT vonhagenmartin associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT wiltfangjens associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT zimmermannjorg associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT andlauertill associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT fischerandre associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT bermpohlfelix associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kraftvivien associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT maturasilke associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT gryaznovaanna associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT falkenbergirina associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT yildizcuneyt associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kirchertilo associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schmidtjulia associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kochmarius associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT gadekatrin associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT trostsarah associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT haußleiterida associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT lambertmartin associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT rohenkohlanjac associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kraftvivien associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT grofpaul associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT hashimotoryota associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT hauserjoanna associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT hermsstefan associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT hoffmannper associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT jimenezesther associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kahnjeanpierre associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kassemlayla associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kuopohsiu associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT katotadafumi associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kelsoejohn associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kittelschneidersarah associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT ferensztajnrochowiakewa associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT konigbarbara associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT kusumiichiro associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT lajegonzalo associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT landenmikael associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT lavebrattcatharina associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT leboyermarion associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT leckbandsusang associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT tortorellaalfonso associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT manchiamirko associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT martinssonlina associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT mccarthymichael associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT mcelroysusanl associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT colomfrancesc associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT mitjansmarina associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT mondimorefrancis associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT monteleonepalmiero associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT nievergeltcaroline associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT nothenmarkus associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT novaktomas associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT odonovanclaire associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT ozakinorio associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT pfennigandrea associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT pisanuclaudia associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT potashjames associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT reifandreas associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT reininghauseva associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT rouleauguy associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT rybakowskijanuszk associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schallingmartin associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schofieldpeter associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schweizerbarbaraw associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT severinogiovanni associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT shillingpauld associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT shimodakazutaka associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT simhandlchristian associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT slaneyclaire associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT squassinaalessio associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT stammthomas associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT stopkovapavla associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT majmario associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT tureckigustavo associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT vietaeduard associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT veehjulia associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT wittstephanie associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT wrightadam associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT zandipeter associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT mitchellphilip associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT bauermichael associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT aldamartin associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT rietschelmarcella associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT mcmahonfrancis associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT schulzethomasg associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT millischervincent associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT clarkscott associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder AT baunebernhard associationofpolygenicscoreandtheinvolvementofcholinergicandglutamatergicpathwayswithlithiumtreatmentresponseinpatientswithbipolardisorder |