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Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying 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.
Contributors
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- By Yasir Abu-Omar, Matthew E. Atkins, Joseph E. Arrowsmith, Alan Ashworth, Rubia Baldassarri, Craig R. Bailey, David J. Barron, Christiana C. Burt, David Cardone, Coralie Carle, Jose Coddens, Alan M. Cohen, Simon Colah, Sarah Conolly, David J. Daly, Helen M. Daly, Stefan G. De Hert, Ravi J. De Silva, Mark Dougherty, John J. Dunning, Maros Elsik, Betsy Evans, Florian Falter, Nigel Farnum, Jens Fassl, Juliet E. Foweraker, Simon P. Fynn, Andrew I. Gardner, Margaret I. Gillham, Martin J. Goddard, Maximilien J. Gourdin, Jon Graham, Stephen J. Gray, Cameron Graydon, Fabio Guarracino, Roger M. O. Hall, Michael Haney, Charles W. Hogue, Ben W. Howes, Bevan Hughes, Siân I. Jaggar, David P. Jenkins, Jörn Karhausen, Todd Kiefer, Khalid Khan, Andrew A. Klein, John D. Kneeshaw, Andrew C. Knowles, Catherine V. Koffel, R. Clive Landis, Trevor W. R. Lee, Clive J. Lewis, Jonathan H. Mackay, Amod Manocha, Jonathan B. Mark, Sarah Marstin, William T. McBride, Kenneth H. McKinlay, Alan F. Merry, Berend Mets, Britta Millhoff, Kevin P. Morris, Samer A. M. Nashef, Andrew Neitzel, Stephane Noble, Rabi Panigrahi, Barbora Parizkova, J. M. Tom Pierce, Mihai V. Podgoreanu, Hans-Joachim Priebe, Paul Quinton, C. Ramaswamy Rajamohan, Doris M. Rassl, Tom Rawlings, Fiona E. Reynolds, Andrew J. Richardson, David Riddington, Andrew Roscoe, Paul H. M. Sadleir, Ving Yuen See Tho, Herve Schlotterbeck, Maura Screaton, Shitalkumar Shah, Harjot Singh, Jon H. Smith, M. L. Srikanth, Yeewei W. Teo, Kamen P. Valchanov, Jean-Pierre van Besouw, Isabeau A. Walker, Stephen T. Webb, Francis C. Wells, John Whitbread, Charles Willmott, Patrick Wouters
- Edited by Jonathan H. Mackay, Joseph E. Arrowsmith
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- Book:
- Core Topics in Cardiac Anesthesia
- Published online:
- 05 April 2012
- Print publication:
- 15 March 2012, pp x-xiii
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Studies on pigment-activating substances in animals I. The separation by paper electrophoresis of chromactivating substances in arthropods
- Francis G. W. Knowles, David B. Carlisle, Marie Dupont-Raabe
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- Journal:
- Journal of the Marine Biological Association of the United Kingdom / Volume 34 / Issue 3 / October 1955
- Published online by Cambridge University Press:
- 11 May 2009, pp. 611-635
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It has been established that many substances can bring about a change in position of pigments in crustacean chromatophores (Florey, 1951). The extracts of certain animal tissues (pituitary, crustacean sinus-gland and post-commissure organs, insect brain and corpora cardiaca) are especially active (Brown, 1940; Knowles, 1953; Dupont-Raabe, 1952; Thomsen, 1943); there is evidence that these tissues intervene in the normal colour change of the animals which possess them and that their products may properly be considered as hormones. On the other hand, many species which do not themselves possess chromatophores (oligochaetes, molluscs, and many insects) have nevertheless been shown to contain substances in their tissues which will, after injection into crustaceans, initiate pigment movements (Scharrer, 1954). It has not yet been ascertained whether these pigment-activating substances chemically resemble normal colour-change hormones or whether the pigment movements they produce are pharmacodynamic effects irrelevant in the study of colour physiology.