3 results
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.
Infection of sheep and monkeys with Langat virus: cross-protection against other viruses of the Russian spring-summer complex
- K. J. O'Reilly, C. E. Gordon Smith, Dolores A. McMahon, A. L. Wilson, J. M. Robertson
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- Journal:
- Journal of Hygiene / Volume 63 / Issue 2 / June 1965
- Published online by Cambridge University Press:
- 15 May 2009, pp. 213-221
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1. The susceptibility of sheep to infection with Langat virus has been studied. No viraemia or symptoms were detected in sheep inoculated either subcutaneously or intracerebrally.
2. Only those sheep inoculated intracerebrally with 106·0–108·0 mouse IC LD 50 of virus developed significant quantities of neutralizing antibody.
3. Two-thirds of sheep vaccinated with varying doses of Langat virus withstood subcutaneous challenge of louping-ill virus followed by intracerebral starch. All the intracerebrally vaccinated sheep survived this form of challenge but no sheep, whether vaccinated subcutaneously or intracerebrally, withstood intracerebral challenge of louping ill.
4. In a field trial, three of ten hoggs vaccinated with Langat virus and exposed to natural louping ill infection at Camlarg and Dalcairnie died of the disease compared with all eight of the non-vaccinated hoggs. At Knockgray, there was no louping ill infection, but 93% of the hoggs from this hirsel developed louping ill antibody after transfer to Camlarg.
5. Monkeys infected intracerebrally, subcutaneously or orally with Langat virus showed a low titre viraemia without clinical symptoms or histological changes in the brain and developed high titres of antibody. Vaccinated monkeys challenged with either Central European tick-borne encephalitis or Kyasanur Forest disease viruses remained healthy compared with control monkeys which showed evidence of disease.
The epidemiology of louping ill in Ayrshire: the first year of studies in sheep
- C. E. Gordon Smith, Dolores A McMahon, K. J O'Reilly, A. L Wilson, J. M Robertson
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- Journal:
- Journal of Hygiene / Volume 62 / Issue 1 / March 1964
- Published online by Cambridge University Press:
- 15 May 2009, pp. 53-68
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1. Following an epizootic of louping ill on certain farms in south-west Ayrshire in 1960, a long-term study of several farms was initiated.
2. The flocks on two hirsels of one farm were studied during spring and early summer of 1961. Although only one lamb death was confirmed as due to louping ill, the infection rates in sentinel hoggs on the two hirsels were 50–60. and 11% respectively. The difference between the hirsels is probably attributable to the difference in the amount of tick habitat on them.
3. The ewes were bled in March and June and their lambs in June. Haemagglutinin inhibition (HI) and neutralization tests revealed that the HI antibody is much shorter lasting than neutralizing antibody. Many ewes, therefore, had neutralizing but not HI antibody. Otherwise agreement between the tests was good. In March almost all the ewes aged 3 years or more had antibody. Of the gimmers (2-year-olds) about two-thirds on one hirsel and one-third on the other had antibody in March: by June almost all the former and about half of the latter had antibody.
4. About two-thirds of the lambs had the same antibody status as their mothers in June and almost all the rest had less antibody than their mothers. Serological evidence suggestive of louping ill without recognizable clinical disease was found in six lambs and a further lamb recovered from clinical disease.
5. Revaccination of two-thirds of the flock failed to cause any detectable change in antibody status.
6. The epidemiology and pathogenesis are discussed in relation to immunity and infection rates, and to the design of control measures.
We are greatly indebted to the late Mr James Murdoch at Dalmellington, Mr John Murdoch at Dalcairnie Farm, and Mr David Murdoch at Knockgray Farm for permission to work on their farms and for all the help they gave us during the study.