Marisol Herrera-Rivero, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Azmeraw T Amare, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M Biernacka, Armin Birner, Micah Cearns, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R Clark, Francesc Colom, Cristiana Cruceanu, Piotr M Czerski, Nina Dalkner, Franziska Degenhardt, Maria Del Zompo, J Raymond DePaulo, Bruno Etain, Peter Falkai, Ewa Ferensztajn-Rochowiak, Andreas J Forstner, Josef Frank, Louise Frisén, Mark A Frye, Janice M Fullerton, Carla Gallo, Sébastien Gard, Julie S Garnham, Fernando S Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Roland Hasler, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Po-Hsiu Kuo, Ichiro Kusumi, Barbara König, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G Leckband, Mario Maj, Mirko Manchia, Cynthia Marie-Claire, Lina Martinsson, Michael J McCarthy, Susan L McElroy, Vincent Millischer, Marina Mitjans, Francis M Mondimore, Palmiero Monteleone, Caroline M Nievergelt, Tomas Novák, Markus M Nöthen, Claire O'Donovan, Norio Ozaki, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B Potash, Andreas Reif, Eva Reininghaus, Hélène Richard-Lepouriel, Gloria Roberts, Guy A Rouleau, Janusz K Rybakowski, Martin Schalling, Peter R Schofield, Klaus Oliver Schubert, Eva C Schulte, Barbara W Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fabian Streit, Fasil Tekola-Ayele, Anbupalam Thalamuthu, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Biju Viswanath, Stephanie H Witt, Peter P Zandi, Martin Alda, Michael Bauer, Francis J McMahon, Philip B Mitchell, Marcella Rietschel, Thomas G Schulze, Bernhard T Baune
{"title":"探索双相情感障碍中锂反应的遗传学。","authors":"Marisol Herrera-Rivero, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Azmeraw T Amare, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M Biernacka, Armin Birner, Micah Cearns, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R Clark, Francesc Colom, Cristiana Cruceanu, Piotr M Czerski, Nina Dalkner, Franziska Degenhardt, Maria Del Zompo, J Raymond DePaulo, Bruno Etain, Peter Falkai, Ewa Ferensztajn-Rochowiak, Andreas J Forstner, Josef Frank, Louise Frisén, Mark A Frye, Janice M Fullerton, Carla Gallo, Sébastien Gard, Julie S Garnham, Fernando S Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Roland Hasler, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Po-Hsiu Kuo, Ichiro Kusumi, Barbara König, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G Leckband, Mario Maj, Mirko Manchia, Cynthia Marie-Claire, Lina Martinsson, Michael J McCarthy, Susan L McElroy, Vincent Millischer, Marina Mitjans, Francis M Mondimore, Palmiero Monteleone, Caroline M Nievergelt, Tomas Novák, Markus M Nöthen, Claire O'Donovan, Norio Ozaki, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B Potash, Andreas Reif, Eva Reininghaus, Hélène Richard-Lepouriel, Gloria Roberts, Guy A Rouleau, Janusz K Rybakowski, Martin Schalling, Peter R Schofield, Klaus Oliver Schubert, Eva C Schulte, Barbara W Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fabian Streit, Fasil Tekola-Ayele, Anbupalam Thalamuthu, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Biju Viswanath, Stephanie H Witt, Peter P Zandi, Martin Alda, Michael Bauer, Francis J McMahon, Philip B Mitchell, Marcella Rietschel, Thomas G Schulze, Bernhard T Baune","doi":"10.1186/s40345-024-00341-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.</p><p><strong>Results: </strong>We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.</p><p><strong>Conclusions: </strong>Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169116/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring the genetics of lithium response in bipolar disorders.\",\"authors\":\"Marisol Herrera-Rivero, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Azmeraw T Amare, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M Biernacka, Armin Birner, Micah Cearns, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R Clark, Francesc Colom, Cristiana Cruceanu, Piotr M Czerski, Nina Dalkner, Franziska Degenhardt, Maria Del Zompo, J Raymond DePaulo, Bruno Etain, Peter Falkai, Ewa Ferensztajn-Rochowiak, Andreas J Forstner, Josef Frank, Louise Frisén, Mark A Frye, Janice M Fullerton, Carla Gallo, Sébastien Gard, Julie S Garnham, Fernando S Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Roland Hasler, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Po-Hsiu Kuo, Ichiro Kusumi, Barbara König, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G Leckband, Mario Maj, Mirko Manchia, Cynthia Marie-Claire, Lina Martinsson, Michael J McCarthy, Susan L McElroy, Vincent Millischer, Marina Mitjans, Francis M Mondimore, Palmiero Monteleone, Caroline M Nievergelt, Tomas Novák, Markus M Nöthen, Claire O'Donovan, Norio Ozaki, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B Potash, Andreas Reif, Eva Reininghaus, Hélène Richard-Lepouriel, Gloria Roberts, Guy A Rouleau, Janusz K Rybakowski, Martin Schalling, Peter R Schofield, Klaus Oliver Schubert, Eva C Schulte, Barbara W Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fabian Streit, Fasil Tekola-Ayele, Anbupalam Thalamuthu, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Biju Viswanath, Stephanie H Witt, Peter P Zandi, Martin Alda, Michael Bauer, Francis J McMahon, Philip B Mitchell, Marcella Rietschel, Thomas G Schulze, Bernhard T Baune\",\"doi\":\"10.1186/s40345-024-00341-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lithium (Li) remains the treatment of choice for bipolar disorders (BP). 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引用次数: 0
摘要
背景：锂（Li）仍然是治疗双相情感障碍（BP）的首选药物。锂具有稳定情绪的作用，有助于减轻躁狂症、抑郁症的长期负担，降低双相情感障碍患者的自杀风险。此外，它还被证明对睡眠和心血管疾病等疾病相关症状有益处。然而，根据临床表现，BP 诊断亚型（如 BP-I 和 BP-II）内部和之间对 Li 治疗的个体反应各不相同。此外，Li 的长期治疗与不良副作用有关，这也是引起人们关注和不坚持治疗的原因，包括出现甲状腺和肾脏疾病等慢性疾病的风险。近年来，锂遗传学联合会（ConLiGen）的研究发现了一些遗传因素，这些因素导致了血压患者对锂治疗反应的差异性。在此，我们利用 ConLiGen 队列（N = 2064）来研究锂对血压影响的遗传基础。为此，我们研究了Li反应和相关基因与精神症状和内科合并症的多基因负荷之间的关系，特别强调了BP-I和BP-II之间的差异：结果：我们发现，用阿尔达量表测量对 Li 治疗的临床反应与 BP-I 患者躁狂、抑郁、药物和酒精滥用、精神病和自杀意念负担的减轻有关，而 BP-II 患者仅与抑郁有关。我们的遗传分析表明，对李的临床反应较强与 BP-I 患者较低的糖尿病和高血压多基因负荷有一定关系，但与 BP-II 无关。此外，我们的研究结果表明，之前与血压中 Li 反应变异有关的一些基因与精神症状，尤其是躁狂和抑郁发作次数，以及糖尿病、高血压和甲状腺机能减退等合并症的多基因负荷有不同的关系：综上所述，我们的研究结果表明，Li 对症状和合并症对血压的影响部分受共同遗传因素的调节，在血压-I 和血压-II 之间存在不同的影响。
Exploring the genetics of lithium response in bipolar disorders.
Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.
Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.
Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
期刊介绍：
The International Journal of Bipolar Disorders is a peer-reviewed, open access online journal published under the SpringerOpen brand. It publishes contributions from the broad range of clinical, psychological and biological research in bipolar disorders. It is the official journal of the ECNP-ENBREC (European Network of Bipolar Research Expert Centres ) Bipolar Disorders Network, the International Group for the study of Lithium Treated Patients (IGSLi) and the Deutsche Gesellschaft für Bipolare Störungen (DGBS) and invites clinicians and researchers from around the globe to submit original research papers, short research communications, reviews, guidelines, case reports and letters to the editor that help to enhance understanding of bipolar disorders.
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