Citations 2
Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study
Ou, Anna , Adli, Mazda , Akiyama, Kazufumi , Akula, Nirmala , Amare, Azmeraw T. , Ardau, Raffaella , Arias, Bárbara , Aubry, Jean‐Michel , Bauer, Michael , Benabarre, Antonio , Bengesser, Susanne , Abesh, Bhattacharjee, Bui, Elise T. , Cervantes, Pablo , Chillotti, Caterina , Cichon, Sven , Clark, Scott R. , Cousins, David A. , Cruceanu, Cristiana , Degenhardt, Franziska , Ferensztajn‐Rochowiak, Ewa , Forstner, Andreas J. , Frisén, Louise , Frye, Mark A. , Gard, Sébastien, Grof, Paul , Gruber, Oliver , Kahn, Jean‐Pierre, Kassem, Layla, Kittel‐Schneider, Sarah , Dalkner, Nina , Laje, Gonzalo, Landén, Mikael , Lavebratt, Catharina , Leckband, Susan G. , López‐Jaramillo, Carlos , Maj, Mario , Mattheisen, Manuel , McCarthy, Michael J. , Mitjans, Marina , Mondimore, Francis M. , Nöthen, Markus M. , Ösby, Urban, Perlis, Roy H. , Pfennig, Andrea , Potash, James B. , Schalling, Martin , Schubert, Klaus Oliver , Schweizer, Barbara , Severino, Giovanni , Shekhtman, Tatyana , Shilling, Paul D. , Shimoda, Kazutaka , Simhandl, Christian , Slaney, Claire , Stamm, Thomas , Tighe, Sarah K., Volkert, Julia, Witt, Stephanie H. , Zandi, Peter P. , Zompo, Maria Del , Ou, Anna , Alda, Martin , Amare, Azmeraw , Arias, Bárbara , Bauer, M , Baune, Bernhard , Biernacka, Joanna , Chen, Hsi-Chung , Clark, Scott , Cruceanu, Cristiana , Czerski, Piotr , DePaulo, J Raymond , Etain, B , Forstner, Andreas J , Frye, Mark , Fullerton, Janice M , Garnham, Julie , Grigoroiu-Serbanescu, Maria , Hashimoto, Ryota , Hauser, Joanna , Heilbronner, Urs , Hou, Liping , Jamain, Stéphane , Kato, Tadafumi , Kuo, Po-Hsiu , Kusumi, Ichiro , Landén, Mikael , Lavebratt, Catharina , Leboyer, Marion , Marie-Claire, Cynthia , McMahon, Francis , Mitchell, Philip B , Mitjans, Marina , Nievergelt, Caroline M , Nöthen, Markus M , Novak, Tomas , Ozaki, Norio , Papiol, Sergi , Reif, Andreas , Reininghaus, Eva , Rietschel, Marcella , Rouleau, Guy Armand , Rybakowski, Janusz K , Schalling, Martin , Schofield, Peter R , Schubert, Klaus Oliver , Schulze, Thomas , Severino, Giovanni , Shilling, Paul , Shimoda, Kazutaka , Squassina, Alessio , Turecki, Gustavo , Vieta, E , Witt, Stephanie H , Wray, Naomi , Del Zompo, Maria , Cichon, Sven , López-Jaramillo, Carlos , Kittel-Schneider, Sarah , McCarthy, Michael , Perlis, Roy H , Kelsoe, John R , Jiang, Qingfei , Alda, Martin , Backlund, Lena , Banzato, Cláudio E. M. , Bellivier, Frank , Biernacka, Joanna M. , Chen, Guo‐Bo , Chen, Hsi‐Chung , Colom, Francesc , Czerski, Piotr M. , Dantas, Clarissa de Rosalmeida , Dayer, Alexandre G. , Étain, Bruno , Falkai, Peter , Fellendorf, Frederike T. , Fullerton, Janice M. , Goes, Fernando , Grigoroiu‐Serbânescu, Maria , Hashimoto, Ryota , Heilbronner, Urs , Herms, Stefan , Hoffmann, Per , Hofmann, Andrea , Jamain, Stéphane , Jiménez, Esther , Kato, Tadafumi , König, Barbara , Kuo, Po‐Hsiu , Dalkner, Nina , Leboyer, Marion , MacQUEEN, GLENDA M. , Manchia, Mirko , Martinsson, Lina , McElroy, Susan L. , McMahon, Francis J. , Monteleone, Palmiero , Novák, Tomáš , Ozaki, Norio , Papiol, Sergi , Reich‐Erkelenz, Daniela , Reif, Andreas , Schofield, Peter R. , Seemüller, Florian , Squassina, Alessio , Stopková, Pavla , Tortorella, Alfonso , Turecki, Gustavo , Vieta, Eduard , Wright, Adam, Young, Trevor
No container title available | October 3, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
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 2,039 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.
Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder.
McCarthy, Michael J. , Mishra, Himanshu , Wei, Heather, Rohr, Kayla E., Maihofer, Adam X. , Ko, Insu, Shilling, Paul D. , Berrettini, Wade H. , Brennand, Kristen , Calabrese, Joseph R. , Frye, Mark A. , Øedegaard, Ketil J. , Zandi, Peter P. , McCarthy, Michael , Shilling, Paul , Brennand, Kristen , Mishra, Himanshu, Nievergelt, Caroline M , Alda, Martin , Coryell, William , Gage, Fred H , Gershon, Elliot S. , McInnis, Melvin G. , Nurnberger, John I , Kelsoe, John R
No container title available | September 7, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Bipolar disorder (BD) is characterized by mood episodes, disrupted circadian rhythms and gray matter reduction in the brain. Lithium is an effective pharmacotherapy for BD, but not all patients respond to treatment. Lithium has neuroprotective properties and beneficial effects on circadian rhythms that may distinguish lithium responders (Li-R) from non-responders (Li-NR). The circadian clock regulates molecular pathways involved in apoptosis and cell survival, but how this overlap impacts BD and/or lithium responsiveness is unknown. In primary fibroblasts from Li-R/Li-NR BD patients and controls, we found patterns of co-expression among circadian clock and cell survival genes that distinguished BD vs. control, and Li-R vs. Li-NR cells. In cellular models of apoptosis using staurosporine (STS), lithium preferentially protected fibroblasts against apoptosis in BD vs. control samples, regardless of Li-R/Li-NR status. When examining the effects of lithium treatment of cells in vitro, caspase activation by lithium correlated with period alteration, but the relationship differed in control, Li-R and Li-NR samples. Knockdown of Per1 and Per3 in mouse fibroblasts altered caspase activity, cell death and circadian rhythms in an opposite manner. In BD cells, genetic variation in PER1 and PER3 predicted sensitivity to apoptosis in a manner consistent with knockdown studies. We conclude that distinct patterns of coordination between circadian clock and cell survival genes in BD may help predict lithium response.