191 results on '"Dalkner N"'
Search Results
2. Reduction of arterial stiffness in depressive individuals responding to multimodal treatment
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Schönthaler, E.M.D., Hamm, C., Reininghaus, B., Dalkner, N., and Reininghaus, E.Z.
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- 2023
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3. Future directions in the field of Bipolar Disorder
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Reininghaus, E.Z., primary, Dalkner, N., additional, L, Wels, additional, Stijic, M., additional, Bechdolf, A., additional, Bellivier, F., additional, Bergink, V., additional, Ceylan, D., additional, Correll, C.U., additional, Etain, B., additional, Fagiolini, A., additional, Geddes, J., additional, Gonzalez-Pinto, A., additional, Goodwin, G., additional, Hajek, T., additional, Henry, C., additional, Kessing, L.V., additional, Kupka, R., additional, Lagerberg, T.V., additional, Landen, M., additional, Licht, R.W., additional, Martinez-Cengotitabengoa, M., additional, Morken, G., additional, Nielsen, R.E., additional, Rietschel, M., additional, Ritter, P., additional, Schulze, T., additional, Scott, J., additional, Severus, E., additional, Squassina, A., additional, Suwalska, A., additional, Vieta, E., additional, Yildiz, A., additional, Reif, A., additional, Manchia, M., additional, and Andreassen, O.A., additional
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- 2024
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4. The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder.
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Queissner, R., Lenger, M., Birner, A., Dalkner, N., Fellendorf, F., Bengesser, S., Platzer, M., Hamm, C., Maget, A., Reininghaus, B., Ratzenhofer, M., Schuller, J., Mangge, H., Kapfhammer, H.P., and Reininghaus, EZ.
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- 2021
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5. The relationship between “Eyes Reading” ability and verbal memory in bipolar disorder
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Dalkner, N., Bengesser, S.A., Birner, A., Fellendorf, F.T., Hamm, C., Platzer, M., Pilz, R., Queissner, R., Rieger, A., Weber, B., Kapfhammer, H.P., Weiss, E.M., and Reininghaus, E.Z.
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- 2019
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6. Epigenetics of the molecular clock and bacterial diversity in bipolar disorder
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Bengesser, S.A., Mörkl, S., Painold, A., Dalkner, N., Birner, A., Fellendorf, F.T., Platzer, M., Queissner, R., Hamm, C., Maget, A., Pilz, R., Rieger, A., Wagner-Skacel, J., Reininghaus, B., Kapfhammer, H.P., Petek, E., Kashofer, K., Halwachs, B., Holzer, P., Waha, A., and Reininghaus, E.Z.
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- 2019
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7. Changes in the tryptophan-kynurenine axis in association to therapeutic response in clinically depressed patients undergoing psychiatric rehabilitation
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Reininghaus, B., Riedrich, K., Dalkner, N., Bengesser, S.A., Birner, A., Platzer, M., Hamm, C., Gostner, J.M., Fuchs, D., and Reininghaus, E.Z.
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- 2018
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8. Gender differences in the association between physical activity and cognitive function in individuals with bipolar disorder
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Fellendorf, F.T., Kainzbauer, N., Platzer, M., Dalkner, N., Bengesser, S.A., Birner, A., Queissner, R., Rauch, P., Hamm, C., Pilz, R., and Reininghaus, E.Z.
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- 2017
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9. Robotics in psychiatry – Fiction or reality?
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Reininghaus, EZ, primary and Dalkner, N, additional
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- 2023
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10. The impact of obesity and metabolic syndrome on clinical and cognitive parameters in bipolar disorder: Results from the BIPFAT/BIPLONG study
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Dalkner, N., primary, Birner, A., additional, Bengesser, S., additional, Guggemos, S., additional, Fellendorf, F., additional, Häussl, A., additional, Lenger, M., additional, Maget, A., additional, Painold, A., additional, Platzer, M., additional, Queissner, R., additional, Schmiedhofer, F., additional, Schönthaler, E., additional, Smolle, S., additional, Stross, T., additional, Tmava-Berisha, A., additional, and Reininghaus, E. Z., additional
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- 2023
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11. A one-year view on the association of metabolic syndrome and cognitive function in bipolar disorder – Preliminary data
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Liebing, S., primary, Dalkner, N., additional, Ischebeck, A., additional, Bengesser, S.A., additional, Birner, A., additional, Fellendorf, F.T., additional, Lenger, M., additional, Maget, A., additional, Kroisenbrunner, H., additional, Häussl, A., additional, Platzer, M., additional, Queissner, R., additional, Schönthaler, E.M.D., additional, Stross, T., additional, Tmava-Berisha, A., additional, and Reininghaus, E.Z., additional
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- 2023
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12. Microbial and metabolic changes in depressive patients after probiotic supplementation
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Maget, A., primary, Lenger, M., additional, Platzer, M., additional, Kohlhammer-Dohr, A., additional, Hamm, C., additional, Mörkl, S., additional, Bengesser, S.A., additional, Fellendorf, F.T., additional, Lahousen-Luxenberger, T., additional, Leitner-Afschar, B., additional, Schöggl, H., additional, Amberger-Otti, D., additional, Wurm, W., additional, Queissner, R., additional, Birner, A., additional, Falzberger, V., additional, Painold, A., additional, Fitz, W., additional, Wagner-Skacel, J., additional, Rieger, A., additional, Unterweger, R., additional, Reininghaus, B., additional, Bastiaanssen, T., additional, Dalkner, N., additional, and Reininghaus, E.Z., additional
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- 2023
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13. The next generation of bipolar disorder researcher in Europe – a program from ECNP Bipolar Disorders Network
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Reininghaus, E., primary, Manchia, M., additional, Wels, L., additional, Dalkner, N., additional, and Andreassen, O.A., additional
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- 2023
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14. Pepper: The socially assistive robot – acceptance and effectiveness by psychiatric inpatients with bipolar disorder – a project description
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Häussl, A., primary, Fellendorf, F., additional, Fleischmann, E., additional, Guggemos, S., additional, Kling, M., additional, Reininghaus, B., additional, Schönthaler, E., additional, Stross, T., additional, Stix, K., additional, Zwigl, I., additional, Paletta, L., additional, Lenger, M., additional, Dalkner, N., additional, and Reininghaus, E., additional
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- 2023
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15. Metacognitive function as a valuable predictive marker in psychiatry: the METACOG project
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Dalkner, N., primary, Fellendorf, F., additional, Tmava-Berisha, A., additional, Schmiedhofer, F., additional, Obermyer-Pietsch, A., additional, Bengesser, S., additional, Platzer, M., additional, Lenger, M., additional, Häussl, A., additional, Schönthaler, E., additional, Stross, T., additional, Wagner-Skacel, J., additional, Harvey, P.D., additional, and Reininghaus, E.Z., additional
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- 2023
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16. Tryptophan metabolism in bipolar disorder
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Fellendorf, F., primary, Platzer, M., additional, Birner, A., additional, Queissner, R., additional, Bengesser, S., additional, Lenger, M., additional, Maget, A., additional, Tmava-Berisha, A., additional, Dalkner, N., additional, Fuchs, D., additional, Gostner, J., additional, and Reininghaus, E., additional
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- 2022
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17. Physical health profile and associated behaviour during the COVID-19 pandemic in patients with bipolar disorder
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Sperling, J.D., primary, Dalkner, N., additional, Berndt, C., additional, Fleischmann, E., additional, Ratzenhofer, M., additional, Martini, J., additional, Pfennig, A., additional, Bauer, M., additional, Reininghaus, E., additional, and Vinberg, M., additional
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- 2022
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18. Outcomes associated with different vaccines in individuals with bipolar disorder and impact on the current COVID-19 pandemic- a systematic review.
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Reininghaus, EZ, Manchia, M, Dalkner, N, Bonkat, N, Squassina, A, Hodl, I, Vieta, E, Reif, A, Hajek, T, Landén, M, Correll, CU, Scott, J, Etain, B, Rietschel, M, Bergink, V, Martinez-Cengotitabengoa, M, Kessing, LV, Fagiolini, A, Bauer, M, Goodwin, G, Gonzalez-Pinto, A, Kupka, RW, Schulze, TG, Lagerberg, TV, Yildiz, A, Henry, C, Morken, G, Ritter, P, Nieslen, RE, Licht, RW, Bechdolf, A, Andreassen, OA, Fellendorf, FT, Reininghaus, EZ, Manchia, M, Dalkner, N, Bonkat, N, Squassina, A, Hodl, I, Vieta, E, Reif, A, Hajek, T, Landén, M, Correll, CU, Scott, J, Etain, B, Rietschel, M, Bergink, V, Martinez-Cengotitabengoa, M, Kessing, LV, Fagiolini, A, Bauer, M, Goodwin, G, Gonzalez-Pinto, A, Kupka, RW, Schulze, TG, Lagerberg, TV, Yildiz, A, Henry, C, Morken, G, Ritter, P, Nieslen, RE, Licht, RW, Bechdolf, A, Andreassen, OA, and Fellendorf, FT
- Abstract
Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.
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- 2022
19. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients (vol 12, 278, 2022)
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Schubert, KO, Thalamuthu, A, Amare, AT, Frank, J, Streit, F, Adl, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Marie-Claire, C, Cearns, M, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Clark, SR, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Degenhardt, F, Del Zompo, M, DePaulo, JR, Etain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Heilbronner, U, Herms, S, Hoffmann, P, Hou, L, Hsu, Y-H, Jamain, S, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, J, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, Konig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nothen, MM, Novak, T, O'Donovan, C, Ozaki, N, Osby, U, Papiol, S, Pfennig, A, Pisanu, C, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Tekola-Ayele, F, Tortorella, A, Turecki, G, Veeh, J, Vieta, E, Witt, SH, Roberts, G, Zandi, PP, Alda, M, Bauer, M, McMahon, FJ, Mitchell, PB, Schulze, TG, Rietschel, M, Baune, BT, Schubert, KO, Thalamuthu, A, Amare, AT, Frank, J, Streit, F, Adl, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Marie-Claire, C, Cearns, M, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Clark, SR, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Degenhardt, F, Del Zompo, M, DePaulo, JR, Etain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Heilbronner, U, Herms, S, Hoffmann, P, Hou, L, Hsu, Y-H, Jamain, S, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, J, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, Konig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nothen, MM, Novak, T, O'Donovan, C, Ozaki, N, Osby, U, Papiol, S, Pfennig, A, Pisanu, C, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Tekola-Ayele, F, Tortorella, A, Turecki, G, Veeh, J, Vieta, E, Witt, SH, Roberts, G, Zandi, PP, Alda, M, Bauer, M, McMahon, FJ, Mitchell, PB, Schulze, TG, Rietschel, M, and Baune, BT
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- 2022
20. Indoleamine 2,3-dioxygenase activity in bipolar disorder
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Fellendorf, F., Maget, A., Queissner, R., Manchia, M., Birner, A., Bengesser, S.A., Lenger, M., Tmava-Berisha, A., Dalkner, N., Fuchs, D., Gostner, J., and Reininghaus, E.Z.
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- 2022
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21. Relationships between metabolic syndrome, body mass index and dark triad personality traits in individuals with affective disorders
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Schönthaler, E., Brugger, F., Baranyi, A., Reininghaus, E., and Dalkner, N.
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- 2022
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22. The accuracy of self-assessment in the Wisconsin card sorting test performance in schizophrenia and bipolar disorder
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Dalkner, N., Gorora, M., Moore, R.C., Depp, C.A., Pinkham, A.E., and Harvey, P.D.
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- 2022
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23. Artificial intelligence enabled playful enhancement of resilience and self-efficacy - the AI-REFIT project
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Reininghaus, E., Lenger, M., Guggemos, S., Dalkner, N., Fleischmann, E., Dietrich, A., Mosbacher, J., Fellner, M., Götz, G., Spat, S., Lutz, T., Russegger, S., Pszeida, M., Schneeberger, M., Draxler, S., and Paletta, L.
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- 2022
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24. Believing processes in individuals with affective disorders during the COVID-19 pandemic
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Fleischmann, E., Tietz, S.L., Wagner-Skacel, J., Angel, H.F., Ratzenhofer, M., Fellendorf, F.T., Schönthaler, E., Bengesser, S.A., Häussl, A., Tmava-Berisha, A., Lenger, M., Körner, C., Seitz, R.J., Reininghaus, E.Z., and Dalkner, N.
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- 2022
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25. The use of a socially assistive robot in individuals with depression during acute psychiatric inpatient treatment – preliminary RCT results
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Haeussl, A., Lenger, M., Dalkner, N., Guggemos, S., Russegger, S., Lodron, G., Uray, M., Orgel, T., Draxler, S., Weiss, W., Pszeida, M., Schneeberger, M., Zuschnegg, J., Lindner-Rabl, S., Schüssler, S., Roller-Wirnsberger, R., Fellner, M., Hartmann, R., Zweytik, E., Pötz, G., Saran, N., Fruhmann, T., Hauptmann, P., Pratter, U., Spat, S., Pfister, R., Macher, M., Ceron, K., Grossegger, C., Sokolov, O., Danilov, M., Reininghaus, E., and Paletta, L.
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- 2022
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26. Physical health profile and associated behavior during the covid-19 pandemic in patients with bipolar disorder
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Sperling, J., Dalkner, N., Berndt, C., Fleischman, E., Ratzenhofer, M., Martini, J., Pfennig, A., Bauer, M., Reiningshaus, E., and Vinberg, M.
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- 2022
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27. Future directions in the field of Bipolar Disorder
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Bauer, M., Bechdolf, A., Bellivier, F., Bergink, V., Ceylan, D., Correll, C.U., Etain, B., Fagiolini, A., Geddes, J., Gonzalez-Pinto, A., Goodwin, G., Hajek, T., Henry, C., Kessing, L.V., Kupka, R., Lagerberg, T.V., Landen, M., Licht, R.W., Martinez-Cengotitabengoa, M., Morken, G., Nielsen, R.E., Rietschel, M., Ritter, P., Schulze, T., Scott, J., Severus, E., Squassina, A., Suwalska, A., Vieta, E., Yildiz, A., Reininghaus, E.Z., Dalkner, N., Wels, L., Stijic, M., Reif, A., Manchia, M., and Andreassen, O.A.
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- 2024
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28. Sex differences in zonulin in affective disorders and associations with current mood symptoms
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Maget, A, primary, Dalkner, N, additional, Hamm, C, additional, Bengesser, SA, additional, Fellendorf, FT, additional, Platzer, M, additional, Queissner, R, additional, Birner, A, additional, Lenger, M, additional, Mörkl, S, additional, Kohlhammer-Dohr, A, additional, Rieger, A, additional, Seidl, M, additional, Mendel, L, additional, Färber, T, additional, Wetzlmair, L, additional, Schwalsberger, K, additional, Amberger-Otti, DV, additional, Schöggl, H, additional, Lahousen, T, additional, Leitner-Afschar, B, additional, Unterweger, R, additional, Zelzer, S, additional, Mangge, H, additional, and Reininghaus, EZ, additional
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- 2021
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29. Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls
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Bengesser, S. A., primary, Hohenberger, H., additional, Tropper, B., additional, Dalkner, N., additional, Birner, A., additional, Fellendorf, F. T., additional, Platzer, M., additional, Rieger, A., additional, Maget, A., additional, Hamm, C., additional, Queissner, R., additional, Pilz, R., additional, Bauer, K., additional, Lenger, M., additional, Mörkl, S., additional, Wagner-Skacel, J., additional, Kapfhammer, H. P., additional, Meier-Allard, N., additional, Stracke, A., additional, Holasek, S. J., additional, Murphy, L., additional, and Reininghaus, E. Z., additional
- Published
- 2021
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30. An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes
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Scott, J., Etain, B., Manchia, M., Brichant-Petitjean, C., Geoffroy, P. A., Schulze, T., Alda, M., Bellivier, F., Amare, A., Ardau, R., Backlund, L., Baune, B., Barboza, A., Benabarre, A., Chaumette, B., Chen, H., Chillotti, C., Clark, S., Colom, F., Del Zompo, M., Dalkner, N., Dantas, C., Ferentinos, P., Garnham, J., Jamain, S., Jimenez, E., Khan, J. -P., Kuo, P., Lavebratt, C., Maj, M., Millischer, V., Monteleone, P., Pisanu, C., Potash, J., Reif, A., Reininghaus, E., Schalling, M., Schofield, P., Schubert, K., Severino, G., Slaney, C., Smith, D., Squassina, A., Tondo, L., Vieta, E., and Witt, S.
- Subjects
Male ,psychometrics ,Bipolar Disorder ,Scale (ratio) ,Computer science ,media_common.quotation_subject ,Sample (statistics) ,Lithium ,Machine learning ,computer.software_genre ,clinimetrics ,03 medical and health sciences ,0302 clinical medicine ,Multidimensional index ,Humans ,genetics ,Quality (business) ,clinical phenotypes ,Biological Psychiatry ,Reliability (statistics) ,Retrospective Studies ,media_common ,Interpretability ,business.industry ,Confounding ,Reproducibility of Results ,Alda scale ,030227 psychiatry ,Psychiatry and Mental health ,Phenotype ,lithium response ,Lithium Compounds ,Female ,Artificial intelligence ,Construct (philosophy) ,business ,computer ,030217 neurology & neurosurgery - Abstract
Objectives The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies.
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- 2019
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31. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- Author
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Mullins, N. Forstner, A.J. O’Connell, K.S. Coombes, B. Coleman, J.R.I. Qiao, Z. Als, T.D. Bigdeli, T.B. Børte, S. Bryois, J. Charney, A.W. Drange, O.K. Gandal, M.J. Hagenaars, S.P. Ikeda, M. Kamitaki, N. Kim, M. Krebs, K. Panagiotaropoulou, G. Schilder, B.M. Sloofman, L.G. Steinberg, S. Trubetskoy, V. Winsvold, B.S. Won, H.-H. Abramova, L. Adorjan, K. Agerbo, E. Al Eissa, M. Albani, D. Alliey-Rodriguez, N. Anjorin, A. Antilla, V. Antoniou, A. Awasthi, S. Baek, J.H. Bækvad-Hansen, M. Bass, N. Bauer, M. Beins, E.C. Bergen, S.E. Birner, A. Bøcker Pedersen, C. Bøen, E. Boks, M.P. Bosch, R. Brum, M. Brumpton, B.M. Brunkhorst-Kanaan, N. Budde, M. Bybjerg-Grauholm, J. Byerley, W. Cairns, M. Casas, M. Cervantes, P. Clarke, T.-K. Cruceanu, C. Cuellar-Barboza, A. Cunningham, J. Curtis, D. Czerski, P.M. Dale, A.M. Dalkner, N. David, F.S. Degenhardt, F. Djurovic, S. Dobbyn, A.L. Douzenis, A. Elvsåshagen, T. Escott-Price, V. Ferrier, I.N. Fiorentino, A. Foroud, T.M. Forty, L. Frank, J. Frei, O. Freimer, N.B. Frisén, L. Gade, K. Garnham, J. Gelernter, J. Giørtz Pedersen, M. Gizer, I.R. Gordon, S.D. Gordon-Smith, K. Greenwood, T.A. Grove, J. Guzman-Parra, J. Ha, K. Haraldsson, M. Hautzinger, M. Heilbronner, U. Hellgren, D. Herms, S. Hoffmann, P. Holmans, P.A. Huckins, L. Jamain, S. Johnson, J.S. Kalman, J.L. Kamatani, Y. Kennedy, J.L. Kittel-Schneider, S. Knowles, J.A. Kogevinas, M. Koromina, M. Kranz, T.M. Kranzler, H.R. Kubo, M. Kupka, R. Kushner, S.A. Lavebratt, C. Lawrence, J. Leber, M. Lee, H.-J. Lee, P.H. Levy, S.E. Lewis, C. Liao, C. Lucae, S. Lundberg, M. MacIntyre, D.J. Magnusson, S.H. Maier, W. Maihofer, A. Malaspina, D. Maratou, E. Martinsson, L. Mattheisen, M. McCarroll, S.A. McGregor, N.W. McGuffin, P. McKay, J.D. Medeiros, H. Medland, S.E. Millischer, V. Montgomery, G.W. Moran, J.L. Morris, D.W. Mühleisen, T.W. O’Brien, N. O’Donovan, C. Olde Loohuis, L.M. Oruc, L. Papiol, S. Pardiñas, A.F. Perry, A. Pfennig, A. Porichi, E. Potash, J.B. Quested, D. Raj, T. Rapaport, M.H. DePaulo, J.R. Regeer, E.J. Rice, J.P. Rivas, F. Rivera, M. Roth, J. Roussos, P. Ruderfer, D.M. Sánchez-Mora, C. Schulte, E.C. Senner, F. Sharp, S. Shilling, P.D. Sigurdsson, E. Sirignano, L. Slaney, C. Smeland, O.B. Smith, D.J. Sobell, J.L. Søholm Hansen, C. Soler Artigas, M. Spijker, A.T. Stein, D.J. Strauss, J.S. Świątkowska, B. Terao, C. Thorgeirsson, T.E. Toma, C. Tooney, P. Tsermpini, E.-E. Vawter, M.P. Vedder, H. Walters, J.T.R. Witt, S.H. Xi, S. Xu, W. Yang, J.M.K. Young, A.H. Young, H. Zandi, P.P. Zhou, H. Zillich, L. Adolfsson, R. Agartz, I. Alda, M. Alfredsson, L. Babadjanova, G. Backlund, L. Baune, B.T. Bellivier, F. Bengesser, S. Berrettini, W.H. Blackwood, D.H.R. Boehnke, M. Børglum, A.D. Breen, G. Carr, V.J. Catts, S. Corvin, A. Craddock, N. Dannlowski, U. Dikeos, D. Esko, T. Etain, B. Ferentinos, P. Frye, M. Fullerton, J.M. Gawlik, M. Gershon, E.S. Goes, F.S. Green, M.J. Grigoroiu-Serbanescu, M. Hauser, J. Henskens, F. Hillert, J. Hong, K.S. Hougaard, D.M. Hultman, C.M. Hveem, K. Iwata, N. Jablensky, A.V. Jones, I. Jones, L.A. Kahn, R.S. Kelsoe, J.R. Kirov, G. Landén, M. Leboyer, M. Lewis, C.M. Li, Q.S. Lissowska, J. Lochner, C. Loughland, C. Martin, N.G. Mathews, C.A. Mayoral, F. McElroy, S.L. McIntosh, A.M. McMahon, F.J. Melle, I. Michie, P. Milani, L. Mitchell, P.B. Morken, G. Mors, O. Mortensen, P.B. Mowry, B. Müller-Myhsok, B. Myers, R.M. Neale, B.M. Nievergelt, C.M. Nordentoft, M. Nöthen, M.M. O’Donovan, M.C. Oedegaard, K.J. Olsson, T. Owen, M.J. Paciga, S.A. Pantelis, C. Pato, C. Pato, M.T. Patrinos, G.P. Perlis, R.H. Posthuma, D. Ramos-Quiroga, J.A. Reif, A. Reininghaus, E.Z. Ribasés, M. Rietschel, M. Ripke, S. Rouleau, G.A. Saito, T. Schall, U. Schalling, M. Schofield, P.R. Schulze, T.G. Scott, L.J. Scott, R.J. Serretti, A. Shannon Weickert, C. Smoller, J.W. Stefansson, H. Stefansson, K. Stordal, E. Streit, F. Sullivan, P.F. Turecki, G. Vaaler, A.E. Vieta, E. Vincent, J.B. Waldman, I.D. Weickert, T.W. Werge, T. Wray, N.R. Zwart, J.-A. Biernacka, J.M. Nurnberger, J.I. Cichon, S. Edenberg, H.J. Stahl, E.A. McQuillin, A. Di Florio, A. Ophoff, R.A. Andreassen, O.A. HUNT All-In Psychiatry
- Abstract
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
- Published
- 2021
32. HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
- Author
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Le Clerc, S, Lombardi, L, Baune, BT, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, JR, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, Colom, F, Millischer, V, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O’Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Pisanu, C, Squassina, A, Le Clerc, S, Lombardi, L, Baune, BT, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, JR, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, Colom, F, Millischer, V, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O’Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Pisanu, C, and Squassina, A
- Abstract
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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- 2021
33. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- Author
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Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, Andreassen, OA, Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, and Andreassen, OA
- Abstract
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
- Published
- 2021
34. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
- Author
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Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, Y-H, Shekhtman, T, AdIi, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, K, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Etain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, JR, Kittel-Schneider, S, Kliwicki, S, Koenig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Noethen, MM, Novak, T, O'Donovan, C, Ozaki, N, Osby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, Vieta, E, Veeh, J, Witt, SH, Wright, A, Zandi, PP, Mitchell, PB, Bauer, M, Alda, M, Rietschel, M, McMahon, FJ, Schulze, TG, Baune, BT, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, Y-H, Shekhtman, T, AdIi, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, K, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Etain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, JR, Kittel-Schneider, S, Kliwicki, S, Koenig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, SL, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Noethen, MM, Novak, T, O'Donovan, C, Ozaki, N, Osby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, Vieta, E, Veeh, J, Witt, SH, Wright, A, Zandi, PP, Mitchell, PB, Bauer, M, Alda, M, Rietschel, M, McMahon, FJ, Schulze, TG, and Baune, BT
- Abstract
Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findin
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- 2021
35. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
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Schubert, KO, Thalamuthu, A, Amare, AT, Frank, J, Streit, F, Adl, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Marie-Claire, C, Cearns, M, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Clark, SR, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Degenhardt, F, Del Zompo, M, DePaulo, JR, Etain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Heilbronner, U, Herms, S, Hoffmann, P, Hou, L, Hsu, Y-H, Jamain, S, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, J, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, Koenig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Noethen, MM, Novak, T, O'Donovan, C, Ozaki, N, Oesby, U, Papiol, S, Pfennig, A, Pisanu, C, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Tekola-Ayele, F, Tortorella, A, Turecki, G, Veeh, J, Vieta, E, Witt, SH, Roberts, G, Zandi, PP, Alda, M, Bauer, M, McMahon, FJ, Mitchell, PB, Schulze, TG, Rietschel, M, Baune, BT, Schubert, KO, Thalamuthu, A, Amare, AT, Frank, J, Streit, F, Adl, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Marie-Claire, C, Cearns, M, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Clark, SR, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Degenhardt, F, Del Zompo, M, DePaulo, JR, Etain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Heilbronner, U, Herms, S, Hoffmann, P, Hou, L, Hsu, Y-H, Jamain, S, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, J, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, Koenig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Noethen, MM, Novak, T, O'Donovan, C, Ozaki, N, Oesby, U, Papiol, S, Pfennig, A, Pisanu, C, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Tekola-Ayele, F, Tortorella, A, Turecki, G, Veeh, J, Vieta, E, Witt, SH, Roberts, G, Zandi, PP, Alda, M, Bauer, M, McMahon, FJ, Mitchell, PB, Schulze, TG, Rietschel, M, and Baune, BT
- Abstract
Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
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- 2021
36. Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls.
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Bengesser, S. A., Hohenberger, H., Tropper, B., Dalkner, N., Birner, A., Fellendorf, F. T., Platzer, M., Rieger, A., Maget, A., Hamm, C., Queissner, R., Pilz, R., Bauer, K., Lenger, M., Mörkl, S., Wagner-Skacel, J., Kapfhammer, H. P., Meier-Allard, N., Stracke, A., and Holasek, S. J.
- Subjects
CIRCADIAN rhythms ,MOLECULAR clock ,GENE expression ,BIPOLAR disorder ,MONONUCLEAR leukocytes ,BODY mass index - Abstract
Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression. ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n = 81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression. ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta
2 = 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.). Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown. [ABSTRACT FROM AUTHOR]- Published
- 2022
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37. The relation between interhemispheric microstructural deficits and illness course in bipolar disorder
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Queissner, R., primary, Seiler, S., additional, Birner, A., additional, Tschernegg, M., additional, Pilz, R., additional, Dalkner, N., additional, Bengesser, S., additional, Platzer, M., additional, Fellendorf, F., additional, Hamm, C., additional, Maget, A., additional, Wagner-Skacel, J., additional, Reininghaus, B., additional, and Reininghaus, E., additional
- Published
- 2019
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38. 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
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Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O'Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O'Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, and Turecki, G
- 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%
- Published
- 2018
39. The role of tryptophan metabolism and food craving in the relationship between obesity and bipolar disorder
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Dalkner, N., primary, Platzer, M., additional, Bengesser, S.A., additional, Birner, A., additional, Fellendorf, F.T., additional, Queissner, R., additional, Painold, A., additional, Mangge, H., additional, Fuchs, D., additional, Reininghaus, B., additional, Kapfhammer, H.P., additional, Holasek, S.J., additional, and Reininghaus, E.Z., additional
- Published
- 2018
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40. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
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Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. 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J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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Artigas M., Van der Auwera S., Azevedo M.H., Bass N., Bau C.H.D., Baune B.T., Bellivier F., Berger K., Biernacka J.M., Bigdeli T.B., Binder E.B., Boehnke M., Boks M.P., Bosch R., Braff D.L., Bryant R., Budde M., Byrne E.M., Cahn W., Casas M., Castelao E., Cervilla J.A., Chaumette B., Cichon S., Corvin A., Craddock N., Craig D., Degenhardt F., Djurovic S., Edenberg H.J., Fanous A.H., Foo J.C., Forstner A.J., Frye M., Fullerton J.M., Gatt J.M., Gejman P.V., Giegling I., Grabe H.J., Green M.J., Grevet E.H., Grigoroiu-Serbanescu M., Gutierrez B., Guzman-Parra J., Hamilton S.P., Hamshere M.L., Hartmann A., Hauser J., Heilmann-Heimbach S., Hoffmann P., Ising M., Jones I., Jones L.A., Jonsson L., Kahn R.S., Kelsoe J.R., Kendler K.S., Kloiber S., Koenen K.C., Kogevinas M., Konte B., Krebs M.-O., Landen M., Lawrence J., Leboyer M., Lee P.H., Levinson D.F., Liao C., Lissowska J., Lucae S., Mayoral F., McElroy S.L., McGrath P., McGuffin P., McQuillin A., Medland S.E., Mehta D., Melle I., Milaneschi Y., Mitchell P.B., Molina E., Morken G., Mortensen P.B., Muller-Myhsok B., Nievergelt C., Nimgaonkar V., Nothen M.M., O'Donovan M.C., Ophoff R.A., Owen M.J., Pato C., Pato M.T., Penninx B.W.J.H., Pimm J., Pistis G., Potash J.B., Power R.A., Preisig M., Quested D., Ramos-Quiroga J.A., Reif A., Ribases M., Richarte V., Rietschel M., Rivera M., Roberts A., Roberts G., Rouleau G.A., Rovaris D.L., Rujescu D., Sanchez-Mora C., Sanders A.R., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Shi J., Shyn S.I., Sirignano L., Sklar P., Smeland O.B., Smoller J.W., Sonuga-Barke E.J.S., Spalletta G., Strauss J.S., Swiatkowska B., Trzaskowski M., Turecki G., Vilar-Ribo L., Vincent J.B., Volzke H., Walters J.T.R., Shannon Weickert C., Weickert T.W., Weissman M.M., Williams L.M., Wray N.R., Zai C.C., Ashley-Koch A.E., Beckham J.C., Hauser E.R., Hauser M.A., Kimbrel N.A., Lindquist J.H., McMahon B., Oslin D.W., Qin X., Mattheisen M., Abdellaoui A., Adams M.J., Agerbo E., Andlauer 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LD SCORE REGRESSION ,Genome-wide association study ,Suicide, Attempted ,3124 Neurology and psychiatry ,0302 clinical medicine ,Risk Factors ,Insomnia ,Suicide attempt ,GWAS ,Suïcidi ,Depression (differential diagnoses) ,Cause of death ,Psychiatry ,0303 health sciences ,Factors de risc en les malalties ,Mental Disorders ,Genetic Correlation ,Genome-wide Association Study ,Pleiotropy ,Polygenicity ,Suicide ,Suicide Attempt ,DEPRESSION ,3. Good health ,Genetic correlation ,Genome-Wide Association Study ,Humans ,Polymorphism, Single Nucleotide ,Depressive Disorder, Major ,Mental illness ,Cohort ,SEX ,medicine.symptom ,Human ,medicine.medical_specialty ,Risk factors in diseases ,BF ,Locus (genetics) ,BEHAVIORS ,Psykiatri ,EVENTS ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,ddc:610 ,GENOME-WIDE ASSOCIATION ,IDEATION ,Socioeconomic status ,METAANALYSIS ,Biological Psychiatry ,030304 developmental biology ,business.industry ,Risk Factor ,Genetic architecture ,THOUGHTS ,RC0321 ,business ,Malalties mentals ,030217 neurology & neurosurgery - Abstract
Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
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- 2022
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41. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
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K., Padyukov, L., Pantel, J., Papezova, H., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Roberts, M., Rujescu, D., Rybakowski, F., Scherag, A., Schmidt, U., Seitz, J., Slachtova, L., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Southam, L., Strober, M., Tortorella, A., Tozzi, F., Treasure, J., Tziouvas, K., van Elburg, A. A., Wade, T. D., Wagner, G., Walton, E., Watson, H. J., Wichmann, H. -E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Adams, M. J., Andlauer, T. F. M., Berger, K., Binder, E. B., Boomsma, D. I., Castelao, E., Colodro-Conde, L., Direk, N., Docherty, A. R., Domenici, E., Domschke, K., Dunn, E. C., Foo, J. C., D, e. Geus E. J. C., Grabe, H. J., Hamilton, S. P., Horn, C., Hottenga, J. -J., Howard, D., Ising, M., Kloiber, S., Levinson, D. F., Lewis, G., Magnusson, P. K. E., Mbarek, H., Middeldorp, C. M., Mostafavi, S., Nyholt, D. R., Penninx, B. W., Peterson, R. E., Pistis, G., Porteous, D. J., Preisig, M., Quiroz, J. A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
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Netherlands Twin Register (NTR) ,cross-disorder genetics ,Medizin ,Genome-wide association study ,Tourette syndrome ,functional genomics ,gene expression ,genetic architecture ,genetic correlation ,GWAS ,neurodevelopment ,pleiotropy ,psychiatric disorders ,Psychiatric genetics ,0302 clinical medicine ,Pleiotropy ,functional genomic ,WIDE ASSOCIATION ,cross-disorder genetic ,0303 health sciences ,Mental Disorders ,Genetic Pleiotropy ,HUMAN BRAIN ,INSIGHTS ,Autism spectrum disorder ,Schizophrenia ,DISEASES ,GENETIC CORRELATIONS ,medicine.medical_specialty ,Neurogenesis ,Quantitative Trait Loci ,BF ,Biology ,GENOTYPE IMPUTATION ,Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics ,Article ,General Biochemistry, Genetics and Molecular Biology ,psychiatric disorder ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Genetic Predisposition to Disease ,Bipolar disorder ,TRANSCRIPTOME ,Psychiatry ,030304 developmental biology ,Gwas ,Psychiatric Genetics ,Cross-disorder Genetics ,Functional Genomics ,Gene Expression ,Genetic Architecture ,Genetic Correlation ,Neurodevelopment ,Psychiatric Disorders ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,IDENTIFICATION ,MUTATIONS ,medicine.disease ,Genetic architecture ,DEMETHYLASE ,RC0321 ,1182 Biochemistry, cell and molecular biology ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
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- 2019
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42. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
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Michael McCarthy, Claire O'Donovan, Urs Heilbronner, Ichiro Kusumi, Eduard Vieta, Liping Hou, Hsi-Chung Chen, Claire Slaney, Maria Grigoroiu-Serbanescu, Kazufumi Akiyama, Michael Bauer, Janusz K. Rybakowski, Frank Bellivier, Marion Leboyer, Katzutaka Shimoda, Palmiero Monteleone, Cristiana Cruceanu, Alessio Squassina, Stephanie H. Witt, Tadafumi Kato, Giovanni Severino, Alfonso Tortorella, J. Raymond DePaulo, Martin Alda, Louise Frisén, Mazda Adl, Martin Schalling, Per Hoffmann, Susan G. Leckband, Jean-Pierre Kahn, Jean-Michel Aubry, Francis J. McMahon, Sven Cichon, Alexandre Dayer, Tatyana Shekhtman, Franziska Degenhardt, James B. Potash, Bruno Etain, Joseph Frank, Antonio Benabarre, Bernhard T. Baune, Gloria Roberts, Ryota Hashimoto, Tomas Novak, Paul D. Shilling, Julia Veeh, Joanna M. Biernacka, Barbara König, Peter Falkai, Philip B. Mitchell, Urban Ösby, Esther Jiménez, Sébastien Gard, Mark A. Frye, Sarah Kittel-Schneider, Layla Kassem, Fasil Tekola-Ayele, Armin Birner, Cynthia Marie-Claire, Raffaella Ardau, Abesh Kumar Bhattacharjee, Stéphane Jamain, Julie Garnham, Guy A. Rouleau, Caterina Chillotti, Piotr M. Czerski, Thomas G. Schulze, Gustavo Turecki, Anbupalam Thalamuthu, Claudia Pisanu, Azmeraw T. Amare, Marina Mitjans, Sergi Papiol, Mario Maj, Bárbara Arias, Janice M. Fullerton, Nina Dalkner, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Eva Z. Reininghaus, Fernando S. Goes, Lena Backlund, Francesc Colom, Catharina Lavebratt, Christian Simhandl, Marcella Rietschel, Micah Cearns, Mikael Landén, Norio Ozaki, Gonzalo Laje, Barbara W. Schweizer, Nirmala Akula, Andrea Pfennig, Yi-Hsiang Hsu, John R. Kelsoe, Lina Martinsson, Markus M. Nöthen, Caroline M. Nievergelt, Pavla Stopkova, Mirko Manchia, Susan L. McElroy, Peter P. Zandi, Scott R. Clark, Joanna Hauser, Andreas J. Forstner, Po-Hsiu Kuo, Andreas Reif, Maria Del Zompo, Paul Grof, Fabian Streit, Ewa Ferensztajn-Rochowiak, Pablo Cervantes, Thomas Stamm, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Marie-Claire, C., Cearns, M., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Clark, S. R., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Etain, B., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Heilbronner, U., Herms, S., Hoffmann, P., Hou, L., Hsu, Y. -H., Jamain, S., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J., Kittel-Schneider, S., Ferensztajn-Rochowiak, E., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Maj, M., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Papiol, S., Pfennig, A., Pisanu, C., Potash, J. B., Reif, A., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shekhtman, T., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Tekola-Ayele, F., Tortorella, A., Turecki, G., Veeh, J., Vieta, E., Witt, S. H., Roberts, G., Zandi, P. P., Alda, M., Bauer, M., Mcmahon, F. J., Mitchell, P. B., Schulze, T. G., Rietschel, M., and Baune, B. T.
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Oncology ,Multifactorial Inheritance ,Treatment response ,medicine.medical_specialty ,Lithium (medication) ,Bipolar disorder ,Poor responder ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Lithium ,DISEASE ,Article ,Cellular and Molecular Neuroscience ,Risk Factors ,Internal medicine ,medicine ,Humans ,Manic-depressive illness ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Depressió psíquica ,METAANALYSIS ,Biological Psychiatry ,Depression (differential diagnoses) ,MANIA ,Depressive Disorder ,Depressive Disorder, Major ,Trastorn bipolar ,Depression ,business.industry ,Major ,medicine.disease ,Pathway analysis ,Liti ,COMPARATIVE EFFICACY ,Psychiatry and Mental health ,Mental depression ,Schizophrenia ,Polygenic risk score ,Esquizofrènia ,Pharmacogenomics ,business ,RC321-571 ,medicine.drug - Abstract
Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
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- 2021
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43. Characterisation of age and polarity at onset in bipolar disorder
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Kalman, Janos, Olde Loohuis, Loes, Vreeker, Annabel, Mcquillin, Andrew, Stahl, Eli, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie, Anderson-Schmidt, Heike, Andreassen, Ole, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade, Boks, Marco, Bromet, Evelyn, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott, Comes, Ashley, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David, Croarkin, Paul, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, del Zompo, Maria, Depaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas, Frye, Mark, Fullerton, Janice, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene, Kelsoe, John, Kennedy, James, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James, Kranz, Thorsten, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William, Leboyer, Marion, Li, Qingqin, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, Mayoral, Fermin, Mcelroy, Susan, Mcinnis, Melvin, McIntosh, Andrew, Medeiros, Helena, Melle, Ingrid, Milanova, Vihra, Mitchell, Philip, Monteleone, Palmiero, Monteleone, Alessio Maria, Nöthen, Markus, Novak, Tomas, Nurnberger, John, O'Brien, Niamh, O'Connell, Kevin, O'Donovan, Claire, O'Donovan, Michael, Opel, Nils, Ortiz, Abigail, Owen, Michael, Pålsson, Erik, Pato, Carlos, Pato, Michele, Pawlak, Joanna, Pfarr, Julia-Katharina, Pisanu, Claudia, Potash, James, Rapaport, Mark, Reich-Erkelenz, Daniela, Reif, Andreas, Reininghaus, Eva, Repple, Jonathan, Richard-Lepouriel, Hélène, Rietschel, Marcella, Ringwald, Kai, Roberts, Gloria, Rouleau, Guy, Schaupp, Sabrina, Scheftner, William, Schmitt, Simon, Schofield, Peter, Schubert, K Oliver, Schulte, Eva, Schweizer, Barbara, Senner, Fanny, Severino, Giovanni, Sharp, Sally, Slaney, Claire, Smeland, Olav, Sobell, Janet, Squassina, Alessio, Stopkova, Pavla, Strauss, John, Tortorella, Alfonso, Turecki, Gustavo, Twarowska-Hauser, Joanna, Veldic, Marin, Vieta, Eduard, Vincent, John, Xu, Wei, Zai, Clement, Zandi, Peter, Di Florio, Arianna, Smoller, Jordan, Biernacka, Joanna, Mcmahon, Francis, Alda, Martin, Müller-Myhsok, Bertram, Koutsouleris, Nikolaos, Falkai, Peter, Freimer, Nelson, Andlauer, Till, Schulze, Thomas, Ophoff, Roel, Depaulo, J. Raymond, Schubert, K. Oliver, Andlauer, Till F.M., Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etain, Bruno, Child and Adolescent Psychiatry / Psychology, Psychiatry, Kalman, J. L., Loohuis, L. M. O., Vreeker, A., Mcquillin, A., Stahl, E. A., Ruderfer, D., Grigoroiu-Serbanescu, M., Panagiotaropoulou, G., Ripke, S., Bigdeli, T. B., Stein, F., Meller, T., Meinert, S., Pelin, H., Streit, F., Papiol, S., Adams, M. J., Adolfsson, R., Adorjan, K., Agartz, I., Aminoff, S. R., Anderson-Schmidt, H., Andreassen, O. A., Ardau, R., Aubry, J. -M., Balaban, C., Bass, N., Baune, B. T., Bellivier, F., Benabarre, A., Bengesser, S., Berrettini, W. H., Boks, M. P., Bromet, E. J., Brosch, K., Budde, M., Byerley, W., Cervantes, P., Chillotti, C., Cichon, S., Clark, S. R., Comes, A. L., Corvin, A., Coryell, W., Craddock, N., Craig, D. W., Croarkin, P. E., Cruceanu, C., Czerski, P. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Djurovic, S., Edenberg, H. J., Al Eissa, M., Elvsashagen, T., Etain, B., Fanous, A. H., Fellendorf, F., Fiorentino, A., Forstner, A. J., Frye, M. A., Fullerton, J. M., Gade, K., Garnham, J., Gershon, E., Gill, M., Goes, F. S., Gordon-Smith, K., Grof, P., Guzman-Parra, J., Hahn, T., Hasler, R., Heilbronner, M., Heilbronner, U., Jamain, S., Jimenez, E., Jones, I., Jones, L., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kennedy, J. L., Kircher, T., Kirov, G., Kittel-Schneider, S., Klohn-Saghatolislam, F., Knowles, J. A., Kranz, T. M., Lagerberg, T. V., Landen, M., Lawson, W. B., Leboyer, M., Li, Q. S., Maj, M., Malaspina, D., Manchia, M., Mayoral, F., Mcelroy, S. L., Mcinnis, M. G., Mcintosh, A. M., Medeiros, H., Melle, I., Milanova, V., Mitchell, P. B., Monteleone, P., Monteleone, A. M., Nothen, M. M., Novak, T., Nurnberger, J. I., O'Brien, N., O'Connell, K. S., O'Donovan, C., O'Donovan, M. C., Opel, N., Ortiz, A., Owen, M. J., Palsson, E., Pato, C., Pato, M. T., Pawlak, J., Pfarr, J. -K., Pisanu, C., Potash, J. B., Rapaport, M. H., Reich-Erkelenz, D., Reif, A., Reininghaus, E., Repple, J., Richard-Lepouriel, H., Rietschel, M., Ringwald, K., Roberts, G., Rouleau, G., Schaupp, S., Scheftner, W. A., Schmitt, S., Schofield, P. R., Schubert, K. O., Schulte, E. C., Schweizer, B., Senner, F., Severino, G., Sharp, S., Slaney, C., Smeland, O. B., Sobell, J. L., Squassina, A., Stopkova, P., Strauss, J., Tortorella, A., Turecki, G., Twarowska-Hauser, J., Veldic, M., Vieta, E., Vincent, J. B., Xu, W., Zai, C. C., Zandi, P. P., Di Florio, A., Smoller, J. W., Biernacka, J. M., Mcmahon, F. J., Alda, M., Muller-Myhsok, B., Koutsouleris, N., Falkai, P., Freimer, N. B., Andlauer, T. F. M., Schulze, T. G., and Ophoff, R. A.
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Paper ,Multifactorial Inheritance ,medicine.medical_specialty ,Autism Spectrum Disorder ,Bipolar disorder ,MESH: Age of Onset ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Medizin ,GWAS ,age at onset ,polarity at onset ,polygenic score ,MESH: Depressive Disorder, Major ,BF ,Genome-wide association study ,Disease ,Psykiatri ,SDG 3 - Good Health and Well-being ,ddc:150 ,Polarity at onset ,Internal medicine ,MESH: Bipolar Disorder ,Polygenic score ,medicine ,Humans ,Academic Psychiatry ,Age of Onset ,Genetic association ,Psychiatry ,MESH: Autism Spectrum Disorder ,Depressive Disorder, Major ,MESH: Humans ,business.industry ,Age at onset ,Heritability ,medicine.disease ,Genetic architecture ,ddc ,Psychiatry and Mental health ,Schizophrenia ,Autism spectrum disorder ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,MESH: Genome-Wide Association Study ,RC0321 ,MESH: Multifactorial Inheritance ,business ,Genome-Wide Association Study - Abstract
BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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- 2021
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44. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
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James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno
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Multifactorial Inheritance ,Bipolar Disorder ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Medizin ,Genome-wide association study ,Major Histocompatibility Complex/genetics ,Major Histocompatibility Complex ,0302 clinical medicine ,Risk Factors ,MESH: Risk Factors ,MESH: Bipolar Disorder ,Chromosomes, Human ,Spectrum disorder ,Genetics ,0303 health sciences ,Bipolar Disorder/genetics ,MESH: Genetic Predisposition to Disease ,MESH: Case-Control Studies ,Phenotype ,Schizophrenia ,Synaptic signaling ,Case-Control Studie ,Human ,Quantitative Trait Loci ,Biology ,MESH: Phenotype ,MESH: Chromosomes, Human ,Article ,03 medical and health sciences ,MESH: Major Histocompatibility Complex ,SDG 3 - Good Health and Well-being ,ddc:570 ,medicine ,Humans ,Genetic Predisposition to Disease ,Bipolar disorder ,Multifactorial Inheritance/genetics ,MESH: Genome, Human ,030304 developmental biology ,MESH: Humans ,Genome, Human ,Risk Factor ,Chromosomes, Human/genetics ,Mental illness ,medicine.disease ,MESH: Quantitative Trait Loci ,Human genetics ,Psychologie ,Case-Control Studies ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,MESH: Genome-Wide Association Study ,Expression quantitative trait loci ,MESH: Multifactorial Inheritance ,Quantitative Trait Loci/genetics ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
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- 2021
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45. Cognitive Function in Individuals with Chronic Hypoparathyroidism - A Prospective Observational Study.
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Tmava-Berisha A, Fahrleitner-Pammer A, Stross T, Geiger S, Geiger C, Fellendorf F, Scherkl M, Finner A, Holl A, Dalkner N, Reininghaus E, and Amrein K
- Abstract
Objective: "Brain fog" is a frequently reported, distressing experience among individuals with chronic hypoparathyroidism, characterized by reduced concentration and reduced ability to perform day-to-day tasks. However, evidence linking chronic hypoparathyroidism to cognitive impairment is limited and inconsistent. This study aimed to explore cognitive function in these patients using a validated neurocognitive test battery, compare results with a matched healthy control group, and analyze the frequency of cognitive impairment based on normative data., Methods: The participants' cognitive performance was tested using a cognitive test battery, including the Trail Making Test A/B, the Color-Word Interference Test, and the California Verbal Learning Test. These tests were used to evaluate the cognitive domains of "attention and processing speed," "verbal learning and memory, " and "executive function." In total, 30 individuals with hypoparathyroidism and 30 healthy controls were included., Results: 24 patients were women (80.0%), with a median age of 44.5±13.1 and a median disease duration of 8.7 years (±5.3). Individuals with chronic hypoparathyroidism showed poorer cognitive performance in "attention and processing speed" (F(1,57) = 8.65, p = 0.005*, η² = 0.13) compared to healthy controls. A significantly higher percentage of patients had cognitive deficits in both "attention and processing speed" (56.7% vs. 3.3%) and "executive function" (60.0% vs. 16.7%)., Conclusions: This study provides evidence that cognitive dysfunction, particularly in "attention and processing speed" is common in chronic hypoparathyroidism. Recognizing cognitive impairment in these patients is crucial, especially when discussing workability. Neuropsychological training as an adjunct therapy strategy may be beneficial in managing these cognitive deficits., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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46. Fine-mapping genomic loci refines bipolar disorder risk genes.
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Koromina M, Ravi A, Panagiotaropoulou G, Schilder BM, Humphrey J, Braun A, Bidgeli T, Chatzinakos C, Coombes B, Kim J, Liu X, Terao C, O 'Connell KS, Adams M, Rolf A, Alda M, Alfredsson L, Andlauer TFM, Andreassen OA, Antoniou A, Baune BT, Bengesser S, Biernacka J, Boehnke M, Bosch R, Cairns MJ, Carr VJ, Casas M, Catts S, Cichon S, Corvin A, Craddock N, Dafnas K, Dalkner N, Dannlowski U, Degenhardt F, Florio AD, Dikeos D, Fellendorf FT, Ferentinos P, Forstner AJ, Forty L, Frye M, Fullerton JM, Gawlik M, Gizer IR, Gordon-Smith K, Green MJ, Grigoroiu-Serbanescu M, Guzman-Parra J, Hahn T, Henskens F, Hillert J, Jablensky AV, Jones L, Jones I, Jonsson L, Kelsoe JR, Kircher T, Kirov G, Kittel-Schneider S, Kogevinas M, Landén M, Leboyer M, Lenger M, Lissowska J, Lochner C, Loughland C, MacIntyre D, Martin NG, Maratou E, Mathews CA, Mayoral F, McElroy SL, McGregor NW, McIntosh A, McQuillin A, Michie P, Mitchell PB, Moutsatsou P, Mowry B, Müller-Myhsok B, Myers RM, Nenadić I, Nievergelt C, Nöthen MM, Nurnberger J, O 'Donovan M, O'Donovan C, Ophoff RA, Owen MJ, Pantelis C, Pato C, Pato MT, Patrinos GP, Pawlak JM, Perlis RH, Porichi E, Posthuma D, Ramos-Quiroga JA, Reif A, Reininghaus EZ, Ribasés M, Rietschel M, Schall U, Schofield PR, Schulze TG, Scott L, Scott RJ, Serretti A, Weickert CS, Smoller JW, Artigas MS, Stein DJ, Streit F, Toma C, Tooney P, Vawter MP, Vieta E, Vincent JB, Waldman ID, Weickert T, Witt SH, Hong KS, Ikeda M, Iwata N, Świątkowska B, Won HH, Edenberg HJ, Ripke S, Raj T, Coleman JRI, and Mullins N
- Abstract
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, CRTC3, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, DPH1, GSDMB, MED24 and THRA in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of BD polygenic risk scores across diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI)., Competing Interests: Competing interests OAA has served as a speaker for Janssen, Lundbeck, and Sunovion and as a consultant for Cortechs.ai. SKS has served as speaker for Janssen, Takeda and Medice Arzneimittel Puetter GmbH & CoKG. EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Abbvie, Adamed, Angelini, Biogen, Biohaven, Boehringer Ingelheim, Casen-Recordati, Celon, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo Smith-Kline, Idorsia, Janssen, Johnson & Johnson, Lundbeck, Newron, Novartis, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris. PBM has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for lectures, and Janssen (Australia) for advisory board membership. MOD and MJO have received grants from Akrivia Health and Takeda Pharmaceuticals for work unrelated to this project.
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- 2024
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47. Theory of mind abilities during the course of bipolar disorder: A longitudinal study using mixed models.
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Stix K, Dalkner N, Bengesser SA, Birner A, Fellendorf FT, Häussl A, Lenger M, Maget A, Painold A, Platzer M, Queissner R, Schmiedhofer F, Schönthaler E, Schwerdtfeger A, Stross T, Tmava-Berisha A, Weber B, Unterrainer HF, and Reininghaus EZ
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- Humans, Female, Male, Longitudinal Studies, Adult, Middle Aged, Neuropsychological Tests, Bipolar Disorder psychology, Bipolar Disorder physiopathology, Theory of Mind physiology
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Theory of mind (ToM) deficits, difficulties in recognizing the intentions, propensities, and beliefs of others have been shown in individuals with bipolar disorder in several studies; however, it is not yet elucidated how ToM abilities changes over the course of bipolar disorder and is related to illness symptoms. This is one of the first longitudinal studies to compare the ToM abilities of euthymic bipolar individuals and healthy controls over a four and a half years period. ToM abilities were measured using the Reading the Mind in the Eyes Test (RMET). A total of 91 euthymic bipolar individuals and 91 healthy controls were included in the analyses. Linear mixed models were used to compare ToM abilities of bipolar individuals and healthy controls. It was found that bipolar individuals scored lower on average on the RMET than healthy controls and that these RMET scores were stable over four and a half years. The results of this study suggest that ToM deficits are a stable (possibly endophenotypic) trait of bipolar disorder. This understanding can contribute to better identification, assessment, and treatment strategies for individuals with bipolar disorder, ultimately improving their overall care and outcome., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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48. Toxoplasma gondii IgG serointensity and cognitive function in bipolar disorder.
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Rensch P, Postolache TT, Dalkner N, Stross T, Constantine N, Dagdag A, Wadhawan A, Mohyuddin F, Lowry CA, Joseph J, Birner A, Fellendorf FT, Finner A, Lenger M, Maget A, Painold A, Queissner R, Schmiedhofer F, Smolle S, Tmava-Berisha A, and Reininghaus EZ
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Background: Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder., Methods: A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ., Results: In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=-0.539, p = 0.005), long delay free recall (r=-0.423, p = 0.035), and immediate recall sum trial 1-5 (r=-0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed., Conclusions: This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships., (© 2024. The Author(s).)
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- 2024
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49. Better understanding of c-reactive protein and leukocytes in psychiatric inpatients with affective disorders: A biopsychosocial approach.
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Kölblinger F, Schönthaler EM, Baranyi A, Stross T, Fellendorf FT, von Lewinski D, Queissner R, Reininghaus EZ, and Dalkner N
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Background: Affective disorders (AD) have been linked to inflammatory processes, although the underlying mechanisms of this relationship are still not fully elucidated. It is hypothesized that demographic, somatic, lifestyle, and personality variables predict inflammatory parameters in AD., Aim: To identify biopsychosocial factors contributing to inflammation in AD measured with two parameters, C-reactive protein (CRP) and leukocytes., Methods: This observational study investigated 186 hospital inpatients diagnosed with AD using demographic parameters, serum inflammatory markers, somatic variables, psychological questionnaires, and lifestyle parameters. Hierarchical regression analyses were used to predict inflammatory markers from demographic, somatic, lifestyle, and personality variables., Results: Analyses showed that 33.8% of the variance of CRP was explained by body mass index and other somatic medication ( e.g. anti-diabetics), age and education, and age of affective disorder diagnosis. For leukocytes, 20.1% of the variance was explained by smoking, diet, metabolic syndrome (MetS), and anti-inflammatory medication ( e.g. non-steroidal anti-inflammatory drugs). Other psychiatric or behavioural variables did not reach significance., Conclusion: Metabolic components seem important, with mounting evidence for a metabolic affective disorder subtype. Lifestyle modifications and psychoeducation should be employed to prevent or treat MetS in AD., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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50. Changes in tryptophan breakdown associated with response to multimodal treatment in depression.
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Reininghaus EZ, Lenger M, Schönthaler EMD, Fellendorf FT, Stross T, Schwarz M, Moll N, Reininghaus B, and Dalkner N
- Abstract
Background: Research on depression showed that dysregulations in tryptophan (TRP), kynurenine (KYN), and its KYN pathway metabolites are key aspects in the development and maintenance of depressive symptoms. In our previous reports, we described sex-specific changes in TRP breakdown as well as changes in KYN and KYN/TRP in association with treatment response and inflammatory and metabolic parameters. However, results of treatment effects on KYN pathway metabolites as well as how pathway changes are related to treatment response remain sparse., Objective: We investigated potential changes of KYN and KYN pathway metabolites in association with therapeutic response of individuals with depression during a six-week multimodal psychiatric rehabilitation program., Methods: 87 participants were divided into treatment responders and non-responders (48 responders, 39 non-responders; 38 male, 49 female; M
age = 51.09; SDage = 7.70) using scores of psychological questionnaires. KYN pathway metabolites serum concentrations as well as their ratios were collected using high performance liquid chromatography. Changes over time (time of admission (t1) vs. time of discharge (t2)) were calculated using repeated measure analyses of (co)variance., Results: Non-responders exhibited higher levels of 3-Hydroxyanthralinic acid (3-HAA), nicotinic acid (NA), and 3-HAA/KYN, independently of measurement time. NA levels decreased, while 3-HAA levels increased over time in both groups, independently of treatment response. 3-HK/KYN levels decreased, while KYN levels increased in non-responders, but not in responders over time., Discussion: The results indicate that some compounds of the KYN pathway metabolites can be altered through multimodal long-term interventions in association with treatment response. Especially the pathway degrading KYN further down to 3-HAA and 3-HK/KYN might be decisive for treatment response in depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Reininghaus, Lenger, Schönthaler, Fellendorf, Stross, Schwarz, Moll, Reininghaus and Dalkner.)- Published
- 2024
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