Citations 2
Exploring the genetics of lithium response in bipolar disorders
Adli, Mazda , Akiyama, Kazufumi , Akula, Nirmala , Amare, Azmeraw T. , Ardau, Raffaella , Aubry, Jean‐Michel , Benabarre, Antonio , Bengesser, Susanne , Bhattacharjee, Abesh Kumar, Birner, Armin , Cearns, Micah , Cervantes, Pablo , Chillotti, Caterina , Cichon, Sven , Clark, Scott R. , Cruceanu, Cristiana , Dalkner, Nina , Zompo, Maria Del , Ferensztajn‐Rochowiak, Ewa , Forstner, Andreas J. , Frank, Josef , Frisén, Louise , Frye, Mark A. , Gard, Sébastien, Grof, Paul , Hsu, Yi‐Hsiang, Kahn, Jean‐Pierre, Kassem, Layla, Kittel‐Schneider, Sarah , Laje, Gonzalo, Landén, Mikael , Lavebratt, Catharina , Leckband, Susan G. , Maj, Mario , McCarthy, Michael J. , Mitjans, Marina , Mondimore, Francis M. , O’Donovan, Claire , Pfennig, Andrea , Pisanu, Claudia , Potash, James B. , Richard-Lepouriel, Hélène , Roberts, Gloria , Schalling, Martin , Schubert, Klaus Oliver , Schulte, Eva C. , Schweizer, Barbara , Severino, Giovanni , Shekhtman, Tatyana , Shilling, Paul D. , Shimoda, Katzutaka, Simhandl, Christian , Slaney, Claire , Stamm, Thomas , Streit, Fabian , Veeh, Julia, Witt, Stephanie H. , Zandi, Peter P. , Bauer, Michael , Witt, Stephanie H , Cichon, Sven , Amare, Azmeraw , Cruceanu, Cristiana , Schulte, Eva , Kittel-Schneider, Sarah , Lavebratt, Catharina , McCarthy, Michael , Pisanu, Claudia , Schubert, Klaus Oliver , Streit, Fabian , Mitjans, Marina , Herrera-Rivero, Marisol , Arias, Bárbara , Aubry, Jean‐Michel , Backlund, Lena , Bellivier, Frank , Biernacka, Joanna M. , Chen, Hsi‐Chung , Colom, Francesc , Czerski, Piotr M. , Dalkner, Nina , Degenhardt, Franziska , DePaulo, J Raymond , Étain, Bruno , Falkai, Peter , Fullerton, Janice M. , Gallo, Carla , Garnham, Julie , Goes, Fernando , Grigoroiu‐Serbânescu, Maria , Hashimoto, Ryota , Hasler, Roland , Hauser, Joanna , Heilbronner, Urs , Herms, Stefan , Hoffmann, Per , Hou, Liping , Jamain, Stéphane , Jiménez, Esther , Kato, Tadafumi , Kelsoe, John R , Kuo, Po‐Hsiu , Kusumi, Ichiro , König, Barbara , Leboyer, Marion , Manchia, Mirko , Marie-Claire, Cynthia , Martinsson, Lina , McElroy, Susan L. , Millischer, Vincent , Monteleone, Palmiero , Nievergelt, Caroline M , Novák, Tomáš , Nöthen, Markus M. , Ozaki, Norio , Papiol, Sergi , Reif, Andreas , Reininghaus, Eva , Rouleau, Guy Armand , Rybakowski, Janusz K , Schofield, Peter R. , Squassina, Alessio , Stopková, Pavla , Tekola‐Ayele, Fasil , Thalamuthu, Anbupalam , Tortorella, Alfonso , Turecki, Gustavo , Vieta, Eduard , Viswanath, Biju , Alda, Martin , McMahon, Francis J. , Mitchell, Philip B , Rietschel, Marcella , Schulze, Thomas , Baune, Bernhard
No container title available | December 2, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract 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=2,064) 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.
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study
Kálmán, János , Papiol, Sergi , Forstner, Andreas J. , Heilbronner, Urs , Degenhardt, Franziska , Adli, Mazda , Adorjan, Kristina , Akula, Nirmala , Alda, Martin , Anderson‐Schmidt, Heike , Andlauer, Till F. M. , Anghelescu, Ion‐George , Ardau, Raffaella , Arias, Bárbara , Arolt, Volker , Aubry, Jean‐Michel , Bartholdi, Kim, Bauer, Michael , Benabarre, Antonio , Bengesser, Susanne , Bhattacharjee, Abesh Kumar, Birner, Armin , Brichant‐Petitjean, Clara, Cervantes, Pablo , Chillotti, Caterina , Cichon, Sven , Clark, Scott R. , Comes, Ashley L. , Cruceanu, Cristiana , Czerski, Piotr M. , Zompo, Maria Del , Dietrich, Detlef E. , Étain, Bruno , Ethofer, Thomas , Falkai, Peter , Fallgatter, Andreas J. , Figge, Christian, Flatau, Laura , Folkerts, Here, Frisén, Louise , Frye, Mark A. , Fullerton, Janice M. , Gade, Katrin , Gard, Sébastien, Grigoroiu‐Serbânescu, Maria , Gryaznova, Anna, Hake, Maria, Jäger, Markus , Jamain, Stéphane , Jiménez, Esther , Juckel, Georg , Kahn, Jean‐Pierre, Kassem, Layla, Kittel‐Schneider, Sarah , Kliwicki, Sebastian , Klohn‐Sagatholislam, Farah, Köller, Manfred , Konrad, Carsten , Lackner, Nina , Laje, Gonzalo, Landén, Mikael , Lavebratt, Catharina , Leboyer, Marion , Leckband, Susan G. , Maj, Mario , Manchia, Mirko , Martinsson, Lina , McCarthy, Michael J. , McMahon, Francis J. , Mitjans, Marina , Mondimore, Francis M. , Nieratschker, Vanessa , Novák, Tomáš , Ösby, Urban, Potash, James B. , Reich‐Erkelenz, Daniela , Reif, Andreas , Reimer, Jens , Reininghaus, Eva Z. , Reitt, Markus , Ripke, Stephan , Schalling, Martin , Scherk, Harald, Schmauß, Max, Schubert, Klaus Oliver , Schulte, Eva C. , Schulz, Sybille, Senner, Fanny , Severino, Giovanni , Shekhtman, Tatyana , Shilling, Paul D. , Simhandl, Christian , Slaney, Claire , Stamm, Thomas , Stegmaier, Sophia, Stierl, Sebastian, Stopková, Pavla , Thiel, Andreas , Tighe, Sarah K., Tortorella, Alfonso , Turecki, Gustavo , Vieta, Eduard , Veeh, Julia, Hagen, Martin von, Wigand, Moritz E. , Wiltfang, Jens , Zandi, Peter P. , Zimmermann, Jörg , Heilbronner, Maria , Etain, B , Vieta, E , Cichon, Sven , Alda, Martin , Ripke, Stephan , Fullerton, Janice M , Strohmaier, Jana , Aubry, Jean‐Michel , Backlund, Lena , Baune, Bernhard , Becker, Thomas M , Bellivier, Frank , Biernacka, Joanna M. , Budde, Monika , Colom, Francesc , Dannlowski, Udo , Dayer, Alexandre G. , DePaulo, J Raymond , Garnham, Julie , Goes, Fernando , Gryaznova, Anna, Hauser, Joanna , Herms, Stefan , Hoffmann, Per , Hou, Liping , Kelsoe, John R , Klöhn-Sagatholislam, Farahnaz, König, Barbara , Lang, Fabian U. , McElroy, Susan L. , Mitchell, Philip B , Monteleone, Palmiero , Nievergelt, Caroline M , Pfennig, Andrea , Reininghaus, Eva , Rouleau, Guy Armand , Rybakowski, Janusz K , Schofield, Peter R. , Spitzer, Carsten , Squassina, Alessio , Witt, Stephanie H. , Wright, A. Jordan , Nöthen, Markus M. , Rietschel, Marcella , Schulze, Thomas , Papiol, Sergi , Heilbronner, Urs , Cruceanu, Cristiana , Czerski, Piotr , Jamain, Stéphane , Grigoroiu-Serbanescu, Maria , Kalman, Janos , Schulte, Eva , Wiltfang, Jens , Andlauer, Till , Kittel-Schneider, Sarah , Lavebratt, Catharina , Leboyer, Marion , Tortorella, Alfonso , McCarthy, Michael , Novak, Tomas , Reif, Andreas , Stopkova, Pavla , Turecki, Gustavo , McMahon, Francis , Arias, Bárbara , Schubert, Klaus Oliver , Mitjans, Marina , Manchia, Mirko
Bipolar Disorders | June 28, 2018 | Volume: 21 | Issue: 1 | Pages: 68-75
Objectives Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early‐onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD‐ and schizophrenia (SCZ)‐associated risk variants is associated with an earlier AAO in BD patients. Methods A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn‐Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD‐ and SCZ‐PRSs and AAO were evaluated with regression models. Results BD‐ and SCZ‐PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. Conclusions The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.