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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.

Amare, Azmeraw T (author)
Thalamuthu, Anbupalam (author)
Schubert, Klaus Oliver (author)
show more...
Fullerton, Janice M (author)
Ahmed, Muktar (author)
Hartmann, Simon (author)
Papiol, Sergi (author)
Heilbronner, Urs (author)
Degenhardt, Franziska (author)
Tekola-Ayele, Fasil (author)
Hou, Liping (author)
Hsu, Yi-Hsiang (author)
Shekhtman, Tatyana (author)
Adli, Mazda (author)
Akula, Nirmala (author)
Akiyama, Kazufumi (author)
Ardau, Raffaella (author)
Arias, Bárbara (author)
Aubry, Jean-Michel (author)
Hasler, Roland (author)
Richard-Lepouriel, Hélène (author)
Perroud, Nader (author)
Backlund, Lena (author)
Karolinska Institutet
Bhattacharjee, Abesh Kumar (author)
Bellivier, Frank (author)
Benabarre, Antonio (author)
Bengesser, Susanne (author)
Biernacka, Joanna M (author)
Birner, Armin (author)
Marie-Claire, Cynthia (author)
Cervantes, Pablo (author)
Chen, Hsi-Chung (author)
Chillotti, Caterina (author)
Karolinska Institutet
Cichon, Sven (author)
Cruceanu, Cristiana (author)
Czerski, Piotr M (author)
Dalkner, Nina (author)
Del Zompo, Maria (author)
DePaulo, J Raymond (author)
Étain, Bruno (author)
Jamain, Stephane (author)
Falkai, Peter (author)
Forstner, Andreas J (author)
Frisen, Louise (author)
Karolinska Institutet
Frye, Mark A (author)
Gard, Sébastien (author)
Garnham, Julie S (author)
Goes, Fernando S (author)
Grigoroiu-Serbanescu, Maria (author)
Fallgatter, Andreas J (author)
Stegmaier, Sophia (author)
Ethofer, Thomas (author)
Biere, Silvia (author)
Petrova, Kristiyana (author)
Schuster, Ceylan (author)
Adorjan, Kristina (author)
Budde, Monika (author)
Heilbronner, Maria (author)
Kalman, Janos L (author)
Kohshour, Mojtaba Oraki (author)
Reich-Erkelenz, Daniela (author)
Schaupp, Sabrina K (author)
Schulte, Eva C (author)
Senner, Fanny (author)
Vogl, Thomas (author)
Anghelescu, Ion-George (author)
Arolt, Volker (author)
Dannlowski, Udo (author)
Dietrich, Detlef (author)
Figge, Christian (author)
Jäger, Markus (author)
Lang, Fabian U (author)
Juckel, Georg (author)
Konrad, Carsten (author)
Reimer, Jens (author)
Schmauß, Max (author)
Schmitt, Andrea (author)
Spitzer, Carsten (author)
von Hagen, Martin (author)
Wiltfang, Jens (author)
Zimmermann, Jörg (author)
Andlauer, Till F M (author)
Fischer, Andre (author)
Bermpohl, Felix (author)
Ritter, Philipp (author)
Matura, Silke (author)
Gryaznova, Anna (author)
Falkenberg, Irina (author)
Yildiz, Cüneyt (author)
Kircher, Tilo (author)
Schmidt, Julia (author)
Koch, Marius (author)
Gade, Kathrin (author)
Trost, Sarah (author)
Haussleiter, Ida S (author)
Lambert, Martin (author)
Rohenkohl, Anja C (author)
Kraft, Vivien (author)
Grof, Paul (author)
Hashimoto, Ryota (author)
Hauser, Joanna (author)
Herms, Stefan (author)
Hoffmann, Per (author)
Jiménez, Esther (author)
Kahn, Jean-Pierre (author)
Kassem, Layla (author)
Kuo, Po-Hsiu (author)
Kato, Tadafumi (author)
Kelsoe, John (author)
Kittel-Schneider, Sarah (author)
Ferensztajn-Rochowiak, Ewa (author)
König, Barbara (author)
Kusumi, Ichiro (author)
Laje, Gonzalo (author)
Landén, Mikael, 1966 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Lavebratt, Catharina (author)
Leboyer, Marion (author)
Leckband, Susan G (author)
Tortorella, Alfonso (author)
Manchia, Mirko (author)
Martinsson, Lina (author)
Karolinska Institutet
McCarthy, Michael J (author)
McElroy, Susan (author)
Colom, Francesc (author)
Millischer, Vincent (author)
Mitjans, Marina (author)
Mondimore, Francis M (author)
Monteleone, Palmiero (author)
Nievergelt, Caroline M (author)
Nöthen, Markus M (author)
Novák, Tomas (author)
O'Donovan, Claire (author)
Ozaki, Norio (author)
Pfennig, Andrea (author)
Pisanu, Claudia (author)
Potash, James B (author)
Reif, Andreas (author)
Reininghaus, Eva (author)
Rouleau, Guy A (author)
Rybakowski, Janusz K (author)
Schalling, Martin (author)
Schofield, Peter R (author)
Schweizer, Barbara W (author)
Severino, Giovanni (author)
Shilling, Paul D (author)
Shimoda, Katzutaka (author)
Simhandl, Christian (author)
Slaney, Claire M (author)
Squassina, Alessio (author)
Stamm, Thomas (author)
Stopkova, Pavla (author)
Maj, Mario (author)
Turecki, Gustavo (author)
Vieta, Eduard (author)
Veeh, Julia (author)
Witt, Stephanie H (author)
Wright, Adam (author)
Zandi, Peter P (author)
Mitchell, Philip B (author)
Bauer, Michael (author)
Alda, Martin (author)
Rietschel, Marcella (author)
McMahon, Francis J (author)
Schulze, Thomas G (author)
Clark, Scott R (author)
Baune, Bernhard T (author)
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 (creator_code:org_t)
2023
2023
English.
In: Molecular psychiatry. - 1476-5578.
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health 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 = 2367) 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 first 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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By the author/editor
Amare, Azmeraw T
Thalamuthu, Anbu ...
Schubert, Klaus ...
Fullerton, Janic ...
Ahmed, Muktar
Hartmann, Simon
show more...
Papiol, Sergi
Heilbronner, Urs
Degenhardt, Fran ...
Tekola-Ayele, Fa ...
Hou, Liping
Hsu, Yi-Hsiang
Shekhtman, Tatya ...
Adli, Mazda
Akula, Nirmala
Akiyama, Kazufum ...
Ardau, Raffaella
Arias, Bárbara
Aubry, Jean-Mich ...
Hasler, Roland
Richard-Lepourie ...
Perroud, Nader
Backlund, Lena
Bhattacharjee, A ...
Bellivier, Frank
Benabarre, Anton ...
Bengesser, Susan ...
Biernacka, Joann ...
Birner, Armin
Marie-Claire, Cy ...
Cervantes, Pablo
Chen, Hsi-Chung
Chillotti, Cater ...
Cichon, Sven
Cruceanu, Cristi ...
Czerski, Piotr M
Dalkner, Nina
Del Zompo, Maria
DePaulo, J Raymo ...
Étain, Bruno
Jamain, Stephane
Falkai, Peter
Forstner, Andrea ...
Frisen, Louise
Frye, Mark A
Gard, Sébastien
Garnham, Julie S
Goes, Fernando S
Grigoroiu-Serban ...
Fallgatter, Andr ...
Stegmaier, Sophi ...
Ethofer, Thomas
Biere, Silvia
Petrova, Kristiy ...
Schuster, Ceylan
Adorjan, Kristin ...
Budde, Monika
Heilbronner, Mar ...
Kalman, Janos L
Kohshour, Mojtab ...
Reich-Erkelenz, ...
Schaupp, Sabrina ...
Schulte, Eva C
Senner, Fanny
Vogl, Thomas
Anghelescu, Ion- ...
Arolt, Volker
Dannlowski, Udo
Dietrich, Detlef
Figge, Christian
Jäger, Markus
Lang, Fabian U
Juckel, Georg
Konrad, Carsten
Reimer, Jens
Schmauß, Max
Schmitt, Andrea
Spitzer, Carsten
von Hagen, Marti ...
Wiltfang, Jens
Zimmermann, Jörg
Andlauer, Till F ...
Fischer, Andre
Bermpohl, Felix
Ritter, Philipp
Matura, Silke
Gryaznova, Anna
Falkenberg, Irin ...
Yildiz, Cüneyt
Kircher, Tilo
Schmidt, Julia
Koch, Marius
Gade, Kathrin
Trost, Sarah
Haussleiter, Ida ...
Lambert, Martin
Rohenkohl, Anja ...
Kraft, Vivien
Grof, Paul
Hashimoto, Ryota
Hauser, Joanna
Herms, Stefan
Hoffmann, Per
Jiménez, Esther
Kahn, Jean-Pierr ...
Kassem, Layla
Kuo, Po-Hsiu
Kato, Tadafumi
Kelsoe, John
Kittel-Schneider ...
Ferensztajn-Roch ...
König, Barbara
Kusumi, Ichiro
Laje, Gonzalo
Landén, Mikael, ...
Lavebratt, Catha ...
Leboyer, Marion
Leckband, Susan ...
Tortorella, Alfo ...
Manchia, Mirko
Martinsson, Lina
McCarthy, Michae ...
McElroy, Susan
Colom, Francesc
Millischer, Vinc ...
Mitjans, Marina
Mondimore, Franc ...
Monteleone, Palm ...
Nievergelt, Caro ...
Nöthen, Markus M
Novák, Tomas
O'Donovan, Clair ...
Ozaki, Norio
Pfennig, Andrea
Pisanu, Claudia
Potash, James B
Reif, Andreas
Reininghaus, Eva
Rouleau, Guy A
Rybakowski, Janu ...
Schalling, Marti ...
Schofield, Peter ...
Schweizer, Barba ...
Severino, Giovan ...
Shilling, Paul D
Shimoda, Katzuta ...
Simhandl, Christ ...
Slaney, Claire M
Squassina, Aless ...
Stamm, Thomas
Stopkova, Pavla
Maj, Mario
Turecki, Gustavo
Vieta, Eduard
Veeh, Julia
Witt, Stephanie ...
Wright, Adam
Zandi, Peter P
Mitchell, Philip ...
Bauer, Michael
Alda, Martin
Rietschel, Marce ...
McMahon, Francis ...
Schulze, Thomas ...
Clark, Scott R
Baune, Bernhard ...
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Psychiatry
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
Articles in the publication
Molecular psychi ...
By the university
University of Gothenburg
Karolinska Institutet

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