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1. Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

Author

Anna H. Ou, Sara B. Rosenthal, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Martin Alda, Azmeraw T. Amare, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Michael Bauer, Bernhard T. Baune, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M. Biernacka, Pablo Cervantes, Guo-Bo Chen, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R. Clark, Francesc Colom, David A. Cousins, Cristiana Cruceanu, Piotr M. Czerski, Clarissa R. Dantas, Alexandre Dayer, Maria Del Zompo, Franziska Degenhardt, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Frederike Tabea Fellendorf, Ewa Ferensztajn-Rochowiak, Andreas J. Forstner, Louise Frisén, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Oliver Gruber, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Tadafumi Kato, Sarah Kittel-Schneider, Barbara König, Po-Hsiu Kuo, Ichiro Kusumi, Nina Lackner, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Carlos A. López Jaramillo, Glenda MacQueen, Mario Maj, Mirko Manchia, Cynthia Marie-Claire, Lina Martinsson, Manuel Mattheisen, Michael J. McCarthy, Susan L. McElroy, Francis J. McMahon, Philip B. Mitchell, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Urban Ösby, Norio Ozaki, Sergi Papiol, Roy H. Perlis, Claudia Pisanu, James B. Potash, Andrea Pfennig, Daniela Reich-Erkelenz, Andreas Reif, Eva Z. Reininghaus, Marcella Rietschel, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, K. Oliver Schubert, Thomas G. Schulze, Barbara W. Schweizer, Florian Seemüller, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Kazutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Sarah K. Tighe, Alfonso Tortorella, Gustavo Turecki, Eduard Vieta, Julia Volkert, Stephanie Witt, Naomi R. Wray, Adam Wright, L. Trevor Young, Peter P. Zandi, and John R. Kelsoe

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Published
2024
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2. Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder

Author

Céline S. Reinbold, Andreas J. Forstner, Julian Hecker, Janice M. Fullerton, Per Hoffmann, Liping Hou, Urs Heilbronner, Franziska Degenhardt, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Raffaella Ardau, Bárbara Arias, Lena Backlund, Antonio Benabarre, Susanne Bengesser, Abesh K. Bhattacharjee, Joanna M. Biernacka, Armin Birner, Cynthia Marie-Claire, Pablo Cervantes, Guo-Bo Chen, Hsi-Chung Chen, Caterina Chillotti, Scott R. Clark, Francesc Colom, David A. Cousins, Cristiana Cruceanu, Piotr M. Czerski, Alexandre Dayer, Bruno Étain, Peter Falkai, Louise Frisén, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Paul Grof, Oliver Gruber, Ryota Hashimoto, Joanna Hauser, Stefan Herms, Stéphane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Nina Lackner, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Carlos A. López Jaramillo, Glenda MacQueen, Mirko Manchia, Lina Martinsson, Manuel Mattheisen, Michael J. McCarthy, Susan L. McElroy, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Urban Ösby, Norio Ozaki, Roy H. Perlis, Andrea Pfennig, Daniela Reich-Erkelenz, Guy A. Rouleau, Peter R. Schofield, K. Oliver Schubert, Barbara W. Schweizer, Florian Seemüller, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Kazutaka Shimoda, Christian Simhandl, Claire M. Slaney, Jordan W. Smoller, Alessio Squassina, Thomas J. Stamm, Pavla Stopkova, Sarah K. Tighe, Alfonso Tortorella, Gustavo Turecki, Julia Volkert, Stephanie H. Witt, Adam J. Wright, L. Trevor Young, Peter P. Zandi, James B. Potash, J. Raymond DePaulo, Michael Bauer, Eva Reininghaus, Tomáš Novák, Jean-Michel Aubry, Mario Maj, Bernhard T. Baune, Philip B. Mitchell, Eduard Vieta, Mark A. Frye, Janusz K. Rybakowski, Po-Hsiu Kuo, Tadafumi Kato, Maria Grigoroiu-Serbanescu, Andreas Reif, Maria Del Zompo, Frank Bellivier, Martin Schalling, Naomi R. Wray, John R. Kelsoe, Martin Alda, Francis J. McMahon, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, and Sven Cichon

Subjects
bipolar disorder, lithium response, microRNA, common variants, genome-wide association study, Psychiatry, RC435-571
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
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3. Erratum to: Online information seeking by patients with bipolar disorder: results from an international multisite survey

Author

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

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Published
2017
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4. Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study

Author

Claire O'Donovan, Gustavo Turecki, Frank Bellivier, Palmiero Monteleone, Tatyana Shekhtman, Bárbara Arias, Paul Grof, Sébastien Gard, Tomas Novak, Maria Del Zompo, Martin Schalling, Sarah Kittel-Schneider, Hsi-Chung Chen, Eduard Vieta, Claire Slaney, Katzutaka Shimoda, J. Raymond DePaulo, Martin Alda, Liping Hou, Kazufumi Akiyama, Louise Frisén, Gonzalo Laje, Maria Grigoroiu-Serbanescu, Mikael Landén, Nirmala Akula, Cristiana Cruceanu, Tadafumi Kato, Marion Leboyer, Lina Martinsson, Alessio Squassina, Andrea Hofmann, James B. Potash, Barbara König, Markus M. Nöthen, Giovanni Severino, Michael McCarthy, Philip B. Mitchell, Mario Maj, Ichiro Kusumi, Caroline M. Nievergelt, Jean-Pierre Kahn, Ryota Hashimoto, Joanna M. Biernacka, Sebastian Kliwicki, Francis J. McMahon, Guy A. Rouleau, Thomas Stamm, Pablo Cervantes, Alexandre Dayer, Julia Volkert, Po-Hsiu Kuo, Urs Heilbronner, Per Hoffmann, Janice M. Fullerton, Raffaella Ardau, Julie Garnham, Scott R. Clark, Layla Kassem, Fasil Tekola-Ayele, Peter R. Schofield, Nina Dalkner, Caterina Chillotti, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Alfonso Tortorella, Adam Wright, Joanna Hauser, Peter P. Zandi, Piotr M. Czerski, Eva Z. Reininghaus, Fernando S. Goes, Jean-Michel Aubry, Antonio Benabarre, Bernhard T. Baune, Thomas G. Schulze, Francesc Colom, Marcella Rietschel, Andrea Pfennig, Catharina Lavebratt, Andreas J. Forstner, Paul D. Shilling, Mazda Adli, Armin Birner, Andreas Reif, Mirko Manchia, Susan G. Leckband, Azmeraw T. Amare, Susan L. McElroy, Michael Bauer, Norio Ozaki, Urban Ösby, Janusz K. Rybakowski, Pavla Stopkova, Esther Jiménez, Christian Simhandl, Abesh Kumar Bhattacharjee, Yi-Hsiang Hsu, John R. Kelsoe, Marina Mitjans, Sergi Papiol, Clara Brichant-Petitjean, Mark A. Frye, Stephanie H. Witt, Franziska Degenhardt, Sven Cichon, Bruno Etain, Lena Backlund, Peter Falkai, Barbara W. Schweizer, Stéphane Jamain, Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Heilbronner, Ur, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi-Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bã¡rbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, Depaulo, J. Raymond, à tain, Bruno, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sã©bastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jimã©nez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, Kã¶nig, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landã©n, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J., Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nã¶then, Markus M., Novã¡k, Toma, O'Donovan, Claire, Ozaki, Norio, à sby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andrea, 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, Thoma, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, Rietschel, Marcella, Mcmahon, Francis J., Schulze, Thomas G., and Baune, Bernhard T.

Subjects
Male, Oncology, Multifactorial Inheritance, Bipolar Disorder, Lithium (medication), Genome-wide association study, THERAPY, chemistry.chemical_compound, ddc:616.89, 0302 clinical medicine, HLA Antigens, Spectrum disorder, Original Investigation, RISK, Mood stabilizer, Middle Aged, GLYCOGEN-SYNTHASE KINASE-3, 3. Good health, PREVALENCE, Treatment Outcome, Schizophrenia, Psychiatry and Mental Health, Female, Schizophrenic Psychology, Genetic Load, GLYCOGEN-SYNTHASE KINASE-3, CYTOKINE PRODUCTION, PROPHYLACTIC LITHIUM, SPECTRUM DISORDER, RISK, PREVALENCE, METAANALYSIS, GENETICS, THERAPY, PROFILE, medicine.drug, Adult, medicine.medical_specialty, Genotype, GENETICS, medicine.drug_class, PROFILE, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Lithium Carbonate, Internal medicine, mental disorders, medicine, Humans, Bipolar disorder, Psychiatry, METAANALYSIS, SPECTRUM DISORDER, Inflammation, business.industry, Lithium carbonate, Odds ratio, CYTOKINE PRODUCTION, medicine.disease, 030227 psychiatry, chemistry, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

IMPORTANCE Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). OBJECTIVES To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. DESIGN, SETTING, AND PARTICIPANTS A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013.Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. MAIN OUTCOMES AND MEASURES Treatment response to lithiumwas defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. RESULTS Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 ? 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95%CI, 1.42-8.41) at the first decile to 2.03 (95%CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines. CONCLUSIONS AND RELEVANCE This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.

Published
2018

5. International multi-site survey on the use of online support groups in bipolar disorder

Author

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

Subjects
Adult, Male, medicine.medical_specialty, Bipolar Disorder, Internationality, Online support groups, Peer support, online support groups, Self-help, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Journal Article, medicine, Humans, survey, 030212 general & internal medicine, Bipolar disorder, self-help, Psychiatry, Generalized estimating equation, Internet, Descriptive statistics, business.industry, Information seeking, Psychiatry and Mental Health, Middle Aged, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Self-Help Groups, The Internet, Female, business, Psychology, Clinical psychology
Abstract

BACKGROUND: Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups.AIMS: To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking.METHODS: The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data.RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the Internet users who looked online for information about bipolar disorder, only 21.0% read or participated in support groups, chats, or forums for bipolar disorder (12.8% of the total sample). Given the benefits reported in prior research, clarification of the role of online support groups in bipolar disorder is needed. With only a minority of patients using online support groups, there are analytical challenges for future studies.

Published
2017
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6. Erratum to:Online information seeking by patients with bipolar disorder: results from an international multisite survey

Author

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

Subjects
medicine.medical_specialty, Published Erratum, Information seeking, lcsh:QP351-495, medicine.disease, lcsh:RC321-571, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, lcsh:Neurophysiology and neuropsychology, 0302 clinical medicine, medicine, Bipolar disorder, Erratum, Psychology, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030217 neurology & neurosurgery, Biological Psychiatry, Clinical psychology
Abstract

Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information.A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data.976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor.Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites.

Published
2017
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7. Internet use by patients with bipolar disorder: Results from an international multisite survey

Author

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

Subjects
Adult, Male, medicine.medical_specialty, Bipolar Disorder, Internationality, Adolescent, media_common.quotation_subject, education, World wide web, Information source, Odds, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Surveys and Questionnaires, mental disorders, medicine, Humans, Bipolar disorder, Young adult, Psychiatry, Internet, Psychiatry and Mental Health, Biological Psychiatry, media_common, Internet use, business.industry, Middle Aged, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Feeling, The Internet, Female, Self Report, Biological psychiatry, business, 030217 neurology & neurosurgery
Abstract

There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar disorder in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important.

Published
2016
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8. Online information seeking by patients with bipolar disorder: results from an international multisite survey

Author

Claire O'Donovan, Biju Viswanath, Beny Lafer, Raffaella Ardau, Kemal Sagduyu, Anne Hvenegaard Lund, Hirohiko Harima, Ahmad Hatim Sulaiman, Rasmus Wentzer Licht, Guy M. Goodwin, Scott Monteith, Vaisnvy Kapur, John R. Geddes, Paul Grof, Chantal Henry, Kirsi Suominen, Eduard Vieta, Ana González-Pinto, Claire Slaney, Stefanie Hassel, Caterina Chillotti, Leonardo Tondo, Yoshitaka Tatebayashi, Yuly Bersudsky, Erik Roj Larsen, Brett Sawchuk, Bruno Etain, Jörn Conell, Błażej Misiak, Patryk Piotrowski, Eric Yat Wo Cheung, Jonas Gildebro, Takako Nakanotani, Chun Lam, René Ernst Nielsen, Seetal Dodd, Amy C. Bilderbeck, Mark Zetin, Michael Bauer, Sabine Choppin, Letizia Bossini, Philipp Ritter, Rodrigo R. Dias, Michael Berk, Diego Hidalgo-Mazzei, Andrea Fagiolini, Ângela Miranda Scippa, Maj Vinberg, Rodrigo A. Munoz, Andreas Reif, Maria Del Zompo, Aleksandra Suwalska, Martin Alda, Anne Duffy, Alberto Bocchetta, Bernhard T. Baune, Yamima Osher, Julie Garnham, Janusz K. Rybakowski, Peter C. Whybrow, Yasushi Okamura, Julia Volkert, Elon Schwartz, Angela Marianne Paredes Castro, Peter Tam, Iñaki Zorrilla, Girish Kunigiri, Tasha Glenn, Rita Bauer, Ute Lewitzka, CHU Henri Mondor [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Perception et Mémoire, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Coping (psychology), medicine.medical_specialty, 020205 medical informatics, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, Journal Article, 0202 electrical engineering, electronic engineering, information engineering, medicine, 030212 general & internal medicine, Bipolar disorder, Psychiatry, Biological Psychiatry, Descriptive statistics, business.industry, Information seeking, Research, medicine.disease, Mental illness, Mental health, 3. Good health, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, The Internet, business, Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Patient education
Abstract

Background Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. Methods A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. Results 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. Conclusion Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites. Electronic supplementary material The online version of this article (doi:10.1186/s40345-016-0058-0) contains supplementary material, which is available to authorized users.

Published
2016
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9. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Author

Christina M. Hultman, Peter R. Schofield, J. Raymond DePaulo, Martin Alda, Szabolcs Szelinger, Susanne Bengesser, Stefan Herms, Alessio Squassina, Gustavo Turecki, Barbara König, Fabian Streit, Jana Strohmaier, Martin Schalling, Maren Lang, Michael McCarthy, Per Hoffmann, Sarah K. Tighe, William Byerley, Jean-Pierre Kahn, Bárbara Arias, Alfonso Tortorella, Francis J. McMahon, William Lawson, Gonzalo Laje, Wade H. Berrettini, Tatyana Shekhtman, Jean-Michel Aubry, Erin N. Smith, Peng Zhang, Stefanie Heilmann-Heimbach, Evaristus A. Nwulia, Thomas B. Barrett, Cinnamon S. Bloss, Nicholas J. Schork, Tatiana Foroud, Antonio Benabarre, Bernhard T. Baune, William Coryell, Giovanni Severino, Sébastien Gard, Michael Bauer, Layla Kassem, Judith A. Badner, Peter P. Zandi, Rebecca McKinney, Paul D. Shilling, Mazda Adli, Pablo Cervantes, John P. Rice, Nirmala Akula, Marcella Rietschel, Maria Grigoroiu-Serbanescu, Armin Birner, David Craig, Caterina Chillotti, Sebastian Kliwicki, Guy A. Rouleau, Alexandre Dayer, Claire Slaney, Thomas Stamm, Piotr M. Czerski, Pamela B. Mahon, Elliot S. Gershon, Susan L. McElroy, Andreas J. Forstner, Sarah E. Bergen, Peter Propping, Johannes Schumacher, Mikael Landén, Marion Leboyer, Janusz K. Rybakowski, Cristiana Cruceanu, Urs Heilbronner, Joanna Hauser, Fernando S. Goes, Howard J. Edenberg, Markus M. Nöthen, Adam Wright, Chunyu Liu, Daniel L. Koller, James B. Potash, Elise T. Bui, Julie Garnham, Caroline M. Nievergelt, William A. Scheftner, Lina Martinsson, Janice M. Fullerton, Maria Del Zompo, Shashi Hitturlingappa, Mirko Manchia, Andreas Reif, Andrea Pfennig, Thomas G. Schulze, Eduard Vieta, Jie Song, Liping Hou, Maria Hipolito, John I. Nurnberger, Louise Frisén, Anna Maaser, Wolfgang Maier, Thomas W. Mühleisen, Andrea Hofmann, Philip B. Mitchell, Clara Brichant-Petitjean, Raffaella Ardau, Joanna M. Biernacka, N. Lackner, Eva Z. Reininghaus, Francesc Colom, Catharina Lavebratt, Francis M. Mondimore, Urban Ösby, Esther Jiménez, Abesh Kumar Bhattacharjee, Marina Mitjans, Tiffany A. Greenwood, Peter Falkai, Stephanie H. Witt, Stéphane Jamain, Sven Cichon, Julia Volkert, Bruno Etain, Lena Backlund, Tomas Novak, Sarah Kittel-Schneider, Franziska Degenhardt, Barbara W. Schweizer, Mark A. Frye, Christian Simhandl, John R. Kelsoe, Sebastian Zöllner, Frank Bellivier, Palmiero Monteleone, Tony Davis, Susan G. Leckband, Mario Maj, Melvin G. McInnis, and Pavla Stopkova

Subjects
Genetics, 0303 health sciences, Genome-wide association study, Odds ratio, Biology, Heritability, medicine.disease, Mental illness, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Intergenic region, Mood, medicine, Bipolar disorder, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. 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 = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10−9; odds ratio = 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
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10. Genetic variants associated with response to lithium treatment in bipolar disorder:a genome-wide association study

Author

Ryota Hashimoto, Andrea Hofmann, Gustavo Turecki, N. Lackner, Philip B. Mitchell, Bárbara Arias, Urban Ösby, J. Raymond DePaulo, Martin Alda, Julie Garnham, Esther Jiménez, Abesh Kumar Bhattacharjee, Peter P. Zandi, Clara Brichant-Petitjean, Frank Bellivier, Marina Mitjans, Palmiero Monteleone, Eduard Vieta, Liping Hou, Eva Z. Reininghaus, Raffaella Ardau, Paul D. Shilling, Mazda Adli, Armin Birner, Marion Leboyer, Lena Backlund, Andreas J. Forstner, David A. Cousins, Francesc Colom, Catharina Lavebratt, K Oliver Schubert, Barbara W. Schweizer, Mario Maj, Kazufumi Akiyama, Antoni Benabarre, Julia Volkert, Alessio Squassina, Marcella Rietschel, Stephanie H. Witt, Gonzalo Laje, Louise Frisén, Jordan W. Smoller, Paul Grof, Tomas Novak, L. Trevor Young, Sven Cichon, Bruno Etain, Ichiro Kusumi, Sarah K. Tighe, Sarah Kittel-Schneider, Florian Seemüller, Jean-Pierre Kahn, Markus M. Nöthen, Tadafumi Kato, Alexandre Dayer, Caroline M. Nievergelt, Mirko Manchia, Francis J. McMahon, Peter R. Schofield, Susanne Bengesser, Po-Hsiu Kuo, Stefan Herms, Scott R. Clark, Piotr M. Czerski, Oliver Gruber, Franziska Degenhardt, Mark A. Frye, Joanna M. Biernacka, Christian Simhandl, Guo-Bo Chen, Adam Wright, Sébastien Gard, Peter Falkai, Carlos Jaramillo, Stéphane Jamain, Roy H. Perlis, Andrea Pfennig, Tatyana Shekhtman, Maria Del Zompo, Clarissa de Rosalmeida Dantas, Thomas G. Schulze, Alfonso Tortorella, Francis M. Mondimore, John R. Kelsoe, Jean-Michel Aubry, Mikael Landén, Andreas Reif, Naomi R. Wray, Martin Schalling, Janice M. Fullerton, Nirmala Akula, Claudio E. M. Banzato, Elise T. Bui, Per Hoffmann, Sebastian Kliwicki, Guy A. Rouleau, Maria Grigoroiu-Serbanescu, Glenda MacQueen, Lina Martinsson, Giovanni Severino, Norio Ozaki, Daniela Reich-Erkelenz, Layla Kassem, Manuel Mattheisen, Pavla Stopkova, Michael Bauer, Caterina Chillotti, Kazutaka Shimoda, Bernhard T. Baune, Janusz K. Rybakowski, Thomas Stamm, Joanna Hauser, Fernando S. Goes, Urs Heilbronner, James B. Potash, Susan L. McElroy, Barbara König, Susan G. Leckband, Michael McCarthy, Hsi-Chung Chen, Claire Slaney, Cristiana Cruceanu, Pablo Cervantes, Hou, Liping, Heilbronner, Ur, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Banzato, Claudio E M, 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, Thoma, Stopkova, Pavla, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie, Wright, Adam, Young, L Trevor, Zandi, Peter P, Potash, James B, Depaulo, J Raymond, Bauer, Michael, Reininghaus, Eva Z, Novák, Toma, Aubry, Jean-Michel, Maj, Mario, Baune, Bernhard T, Mitchell, Philip B, Vieta, Eduard, Frye, Mark A, Rybakowski, Janusz K, Kuo, Po-Hsiu, Kato, Tadafumi, Grigoroiu-Serbanescu, Maria, Reif, Andrea, Del Zompo, Maria, Bellivier, Frank, Schalling, Martin, Wray, Naomi R, Kelsoe, John R, Alda, Martin, Rietschel, Marcella, Mcmahon, Francis J, and Schulze, Thomas G

Subjects
Male, Glial Cell Line-Derived Neurotrophic Factor Receptors, Bipolar Disorder, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Bipolar Disorder/drug therapy/genetics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, ddc:616.89, 0302 clinical medicine, Genetic variation, Medicine, Humans, Bipolar disorder, Prospective Studies, Allele, Polymorphism, Lithium Compounds/therapeutic use, Genetics, business.industry, Medicine (all), Genetic Variation, General Medicine, Single Nucleotide, Middle Aged, medicine.disease, Polymorphism, Single Nucleotide/genetics, 030227 psychiatry, 3. Good health, Phenotype, Treatment Outcome, Female, Genome-Wide Association Study, Lithium Compounds, business, 030217 neurology & neurosurgery, Imputation (genetics), Pharmacogenetics, Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics
Abstract

BACKGROUND: Lithium 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.METHODS: Here, 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.FINDINGS: A 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).INTERPRETATION: The 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.FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Published
2016
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11. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Author

Philip B. Mitchell, Clara Brichant-Petitjean, Raffaella Ardau, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Sebastian Zöllner, Christina M. Hultman, Shashi Hitturlingappa, Maria Hipolito, Louise Frisén, Thomas W. Mühleisen, Layla Kassem, Christian Simhandl, Urban Ösby, Frank Bellivier, Peter Falkai, Alessio Squassina, Jana Strohmaier, Esther Jiménez, Palmiero Monteleone, Caterina Chillotti, Stéphane Jamain, Peter P. Zandi, Abesh Kumar Bhattacharjee, Tony Davis, Sarah K. Tighe, William Byerley, Jean-Pierre Kahn, Michael Bauer, Nicholas J. Schork, Joanna Hauser, Andreas J. Forstner, Francis J. McMahon, Peter Propping, Marina Mitjans, Tiffany A. Greenwood, Alfonso Tortorella, Fernando S. Goes, Szabolcs Szelinger, Tomas Novak, Erin N. Smith, Andrea Pfennig, Susan G. Leckband, Pablo Cervantes, Sarah Kittel-Schneider, Sébastien Gard, Adam Wright, Tatiana Foroud, Joanna M. Biernacka, Jean-Michel Aubry, Marcella Rietschel, Elliot S. Gershon, Janusz K. Rybakowski, John R. Kelsoe, Stephanie H. Witt, Elise T. Bui, Sarah E. Bergen, Tatyana Shekhtman, Thomas G. Schulze, Sven Cichon, Julia Volkert, Thomas Stamm, Eduard Vieta, Jie Song, Liping Hou, Markus M. Nöthen, Bruno Etain, Mikael Landén, Caroline M. Nievergelt, Mirko Manchia, William Coryell, Howard J. Edenberg, Andreas Reif, Urs Heilbronner, Gonzalo Laje, Lena Backlund, Wade H. Berrettini, Martin Schalling, Franziska Degenhardt, Susan L. McElroy, Mario Maj, Francis M. Mondimore, Peng Zhang, Stefanie Heilmann-Heimbach, Janice M. Fullerton, Daniel L. Koller, James B. Potash, Michael McCarthy, Barbara W. Schweizer, Rebecca McKinney, Nirmala Akula, Sebastian Kliwicki, Guy A. Rouleau, N. Lackner, William Lawson, Melvin G. McInnis, Eva Z. Reininghaus, Maria Grigoroiu-Serbanescu, Pavla Stopkova, Francesc Colom, Catharina Lavebratt, Judith A. Badner, Mark A. Frye, Alexandre Dayer, Giovanni Severino, Maren Lang, John P. Rice, Per Hoffmann, William A. Scheftner, Lina Martinsson, Pamela B. Mahon, Piotr M. Czerski, Paul D. Shilling, Mazda Adli, Armin Birner, David Craig, Gustavo Turecki, Bárbara Arias, Evaristus A. Nwulia, Thomas B. Barrett, Cinnamon S. Bloss, Marion Leboyer, Chunyu Liu, Maria Del Zompo, Antonio Benabarre, Bernhard T. Baune, Fabian Streit, John I. Nurnberger, Barbara König, Anna Maaser, Wolfgang Maier, Julie Garnham, Claire Slaney, Johannes Schumacher, Cristiana Cruceanu, J. Raymond DePaulo, Martin Alda, Andrea Hofmann, Hou, Liping, Bergen, Sarah E., Akula, Nirmala, Song, Jie, Hultman, Christina M., Landén, Mikael, Adli, Mazda, Alda, Martin, Ardau, Raffaella, Arias, Barbara, 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, Ur, 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, Toma, Nurnberger, John I., Nwulia, Evaristus A., Ösby, Urban, Pfennig, Andrea, Potash, James B., Propping, Peter, Reif, Andrea, Reininghaus, Eva, Rice, John, Rietschel, Marcella, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Scheftner, William A., Schofield, Peter R., Schork, Nicholas J., Schulze, Thomas G., Schumacher, Johanne, Schweizer, Barbaraw., Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Simhandl, Christian, Slaney, Claire M., Smith, Erin N., Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolc, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie H., Wright, Adam, Zandi, Peter P., Zhang, Peng, Zollner, Sebastian, and Mcmahon, Francis J.

Subjects
Male, 0301 basic medicine, Bipolar Disorder, Receptor, ErbB-2, Genome-wide association study, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, ddc:616.89, 0302 clinical medicine, Genetic, Molecular Biology, Genetics, Genetics (clinical), medicine, Humans, Bipolar disorder, Genetic association, Chromosomes, Human, X, Association Studies Articles, Case-control study, General Medicine, Odds ratio, Heritability, medicine.disease, 3. Good health, 030104 developmental biology, Meta-analysis, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
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

12. Multi-level biomarker analysis of nitric oxide synthase isoforms in bipolar disorder and adult ADHD

Author

Klaus-Peter Lesch, Brigitte Schmidt, Alexandra Gessner, Heike Weber, Sarah Kittel-Schneider, Susanne Hempel, Andreas Reif, Juliane Kopf, Andrea Meyer, Julia Volkert, Carolin Leistner, Martin Reuß, Psychiatrie & Neuropsychologie, and RS: MHeNs - R3 - Neuroscience

Subjects
Adult, Male, medicine.medical_specialty, Genotype, Nitric Oxide Synthase Type III, Metabolite, NOS1, Nitric Oxide Synthase Type I, Polymorphism, Single Nucleotide, Nitric oxide, Young Adult, chemistry.chemical_compound, Internal medicine, medicine, Humans, Attention deficit hyperactivity disorder, genetic polymorphism, Pharmacology (medical), Bipolar disorder, Pharmacology, Genetics, bipolar disorder, biology, Haplotype, biomarkers, attention deficit-hyperactivity disorder, Middle Aged, medicine.disease, Nitric oxide synthase, Psychiatry and Mental health, Endocrinology, Real-time polymerase chain reaction, Haplotypes, chemistry, Attention Deficit Disorder with Hyperactivity, biology.protein, Female
Abstract

Introduction: Several studies have shown altered levels of nitric oxide (NO) and its stable metabolites (NOx-) in blood and cerebrospinal fluid of psychiatric patients. The aim of our study was to replicate previous findings and investigate the influence of the nitrinergic system in bipolar disorder and adult attention-deficit/hyperactivity disorder (aADHD) in particular. Methods: The concentrations of NO2- and NO3- in peripheral blood in a sample of aADHD, bipolar disorder (BPD) and controls were analysed. The sample was genotyped for a three marker haplotype in the NOS3 gene (rs2070744, rs1799983 and Intron 4 VNTR) and for genetic variants of the NOS1 gene ( NOS1 ex 1c, NOS1 ex 1f). Finally, qRT PCR was performed. Results: We found significantly lower NOx- levels in BPD ( px- levels ( p=0.05). Conclusion: We could replicate and extend previous findings showing altered NOx- levels in BPD and an influence of NOS3 rs2070744 on NOS3 expression and NOx- concentration. Together, these data point to a role of the nitrinergic pathway in BPD.

Published
2015

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