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Association of poly...
Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
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Amare, A. T. (author)
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Schubert, K. O. (author)
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Hou, L. (author)
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show more...
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Clark, S. R. (author)
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Papiol, S. (author)
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Cearns, M. (author)
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Heilbronner, U. (author)
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Degenhardt, F. (author)
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Tekola-Ayele, F. (author)
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Hsu, Y. H. (author)
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Shekhtman, T. (author)
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AdIi, M. (author)
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Akula, N. (author)
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Akiyama, K. (author)
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Ardau, R. (author)
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Arias, B. (author)
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Aubry, J. M. (author)
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- Backlund, L. (author)
- Karolinska Institutet
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Bhattacharjee, K. (author)
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Bellivier, F. (author)
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Benabarre, A. (author)
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Bengesser, S. (author)
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Biernacka, J. M. (author)
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Birner, A. (author)
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Brichant-Petitjean, C. (author)
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Cervantes, P. (author)
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Chen, H. C. (author)
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- Chillotti, C. (author)
- Karolinska Institutet
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Cichon, S. (author)
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Cruceanu, C. (author)
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Czerski, P. M. (author)
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Dalkner, N. (author)
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Dayer, A. (author)
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Del Zompo, M. (author)
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DePaulo, J. R. (author)
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Etain, B. (author)
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Jamain, S. (author)
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Falkai, P. (author)
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Forstner, A. J. (author)
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- Frisen, L. (author)
- Karolinska Institutet
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Frye, M. A. (author)
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Fullerton, J. M. (author)
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Gard, S. (author)
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Garnham, J. S. (author)
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Goes, F. S. (author)
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Grigoroiu-Serbanescu, M. (author)
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Grof, P. (author)
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Hashimoto, R. (author)
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Hauser, J. (author)
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Herms, S. (author)
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Hoffmann, P. (author)
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Hofmann, A. (author)
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Jimenez, E. (author)
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Kahn, J. P. (author)
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Kassem, L. (author)
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Kuo, P. H. (author)
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Kato, T. (author)
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Kelsoe, J. R. (author)
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Kittel-Schneider, S. (author)
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Kliwicki, S. (author)
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Konig, B. (author)
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Kusumi, I. (author)
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Laje, G. (author)
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- Landén, Mikael, 1966 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Lavebratt, C. (author)
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- Leboyer, M. (author)
- Karolinska Institutet
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Leckband, S. G. (author)
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Tortorella, A. (author)
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- Manchia, M. (author)
- Karolinska Institutet
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Martinsson, L. (author)
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McCarthy, M. J. (author)
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McElroy, S. L. (author)
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Colom, F. (author)
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Mitjans, M. (author)
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Mondimore, F. M. (author)
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Monteleone, P. (author)
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Nievergelt, C. M. (author)
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Nothen, M. M. (author)
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Novak, T. (author)
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O'Donovan, C. (author)
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Ozaki, N. (author)
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Osby, U. (author)
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Pfennig, A. (author)
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Potash, J. B. (author)
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Reif, A. (author)
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Reininghaus, E. (author)
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Rouleau, G. A. (author)
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Rybakowski, J. K. (author)
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Schalling, M. (author)
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Schofield, P. R. (author)
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Schweizer, B. W. (author)
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Severino, G. (author)
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Shilling, P. D. (author)
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Shimoda, K. (author)
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Simhandl, C. (author)
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Slaney, C. M. (author)
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Squassina, A. (author)
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Stamm, T. (author)
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Stopkova, P. (author)
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Maj, M. (author)
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Turecki, G. (author)
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Vieta, E. (author)
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Veeh, J. (author)
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Witt, S. H. (author)
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Wright, A. (author)
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Zandi, P. P. (author)
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Mitchell, P. B. (author)
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Bauer, M. (author)
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Alda, M. (author)
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Rietschel, M. (author)
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McMahon, F. J. (author)
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Schulze, T. G. (author)
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Baune, B. T. (author)
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(creator_code:org_t)
- 2020-03-16
- 2021
- English.
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 2457-2470
- Related links:
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https://research.vu....
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
Close
- 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 findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- pharmacological-treatments
- prophylactic lithium
- augmentation
- risk
- predictors
- genetics
- efficacy
- polarity
- therapy
- agents
- Biochemistry & Molecular Biology
- Neurosciences & Neurology
- Psychiatry
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Amare, A. T.
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Schubert, K. O.
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Hou, L.
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Clark, S. R.
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Papiol, S.
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Cearns, M.
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show more...
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Heilbronner, U.
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Degenhardt, F.
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Tekola-Ayele, F.
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Hsu, Y. H.
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Shekhtman, T.
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AdIi, M.
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Akula, N.
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Akiyama, K.
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Ardau, R.
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Arias, B.
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Aubry, J. M.
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Backlund, L.
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Bhattacharjee, K ...
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Bellivier, F.
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Benabarre, A.
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Bengesser, S.
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Biernacka, J. M.
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Birner, A.
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Brichant-Petitje ...
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Cervantes, P.
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Chen, H. C.
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Chillotti, C.
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Cichon, S.
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Cruceanu, C.
-
Czerski, P. M.
-
Dalkner, N.
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Dayer, A.
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Del Zompo, M.
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DePaulo, J. R.
-
Etain, B.
-
Jamain, S.
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Falkai, P.
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Forstner, A. J.
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Frisen, L.
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Frye, M. A.
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Fullerton, J. M.
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Gard, S.
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Garnham, J. S.
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Goes, F. S.
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Grigoroiu-Serban ...
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Grof, P.
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Hashimoto, R.
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Hauser, J.
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Herms, S.
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Hoffmann, P.
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Hofmann, A.
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Jimenez, E.
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Kahn, J. P.
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Kassem, L.
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Kuo, P. H.
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Kato, T.
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Kelsoe, J. R.
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Kittel-Schneider ...
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Kliwicki, S.
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Konig, B.
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Kusumi, I.
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Laje, G.
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Landén, Mikael, ...
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Lavebratt, C.
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Leboyer, M.
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Leckband, S. G.
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Tortorella, A.
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Manchia, M.
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Martinsson, L.
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McCarthy, M. J.
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McElroy, S. L.
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Colom, F.
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Mitjans, M.
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Mondimore, F. M.
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Monteleone, P.
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Nievergelt, C. M ...
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Nothen, M. M.
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Novak, T.
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O'Donovan, C.
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Ozaki, N.
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Osby, U.
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Pfennig, A.
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Potash, J. B.
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Reif, A.
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Reininghaus, E.
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Rouleau, G. A.
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Rybakowski, J. K ...
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Schalling, M.
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Schofield, P. R.
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Schweizer, B. W.
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Severino, G.
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Shilling, P. D.
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Shimoda, K.
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Simhandl, C.
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Slaney, C. M.
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Squassina, A.
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Stamm, T.
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Stopkova, P.
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Maj, M.
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Turecki, G.
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Vieta, E.
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Veeh, J.
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Witt, S. H.
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Wright, A.
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Zandi, P. P.
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Mitchell, P. B.
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Bauer, M.
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Alda, M.
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Rietschel, M.
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McMahon, F. J.
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Schulze, T. G.
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Baune, B. T.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Molecular Psychi ...
- By the university
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University of Gothenburg
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Karolinska Institutet