3 results
Comparison of sleep microarchitecture in screen failure subjects with insomnia complaints and randomized subjects from two phase 3 studies on insomnia disorder
- T. Di Marco, Y. Dauvilliers, T. Scammell, I. Djonlagic, A. Datta, G. Zammit, D. Seboek Kinter, N. Tjiptarto, J. Donoghue
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S269-S270
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Introduction
Daridorexant, a dual orexin receptor antagonist, was shown to be effective and safe in improving sleep and daytime functioning in subjects with insomnia in two Phase 3 studies. All patients screened had subjective insomnia, but many did not meet the study eligibility criteria.
ObjectivesAs the randomized subjects represent only a subsection of the real-world population, we analyzed differences in sleep microarchitecture between included and excluded subjects in both studies.
MethodsOut of 7016 screened subjects, 1851 randomized (included) subjects and 602 screen-failure (SF, excluded) subjects that had at least 1 scored eligibility polysomnography available, were included in this analysis. For the remaining SF subjects, no scored polysomnography was available. The randomized subjects met the DSM 5 insomnia disorder criteria and objective and subjective criteria for disrupted sleep. The main reasons for the 602 SF subjects were not meeting at least 1 objective sleep criteria for sleep onset latency, sleep maintenance, or total sleep time, however all excluded subjects had subjective insomnia. Delta (1-3Hz), theta (4-7Hz), alpha (8-12Hz), and beta (13-38Hz), band spectral power of sleep EEGs were estimated using multi-taper spectrograms (2s window/1s overlap). Relative power was computed using the sum of these four band powers within the 2s window as the denominator. The resulting relative and band power ratios were then aggregated to 30s epochs and assessed by sleep stages (N1, N2, N3, REM, Awake). Sleep spindles (amplitude, peak frequency, oscillation count, symmetry index, slow oscillation phase peak, duration, density, and dispersion) were calculated in N2 sleep using an open-source Luna package. Statistical analysis was done using a univariate analysis of spindle and spectral features via linear mixed-effects regression.
ResultsAge and sex distribution were similar between groups (Median age: 59vs59 years and 68%vs70% Females for included and excluded subjects, respectively). Included subjects had higher relative alpha power (5.6%; p<0.001) and lower relative delta power (-2.3%; p0.031) in N1 than excluded subjects. The mean relative spectral power did not differ significantly for other relative powers in N1 and for any relative powers in stages N2, N3, REM and AWAKE. Included subjects had lower spindle density (-9.8%; p0.005) than excluded subjects. Other spindle features did not significantly differ between the groups.
ConclusionsThis comparison of sleep architecture between included and excluded subjects, showed only minor differences in sleep microarchitecture. This suggests that the sleep microarchitecture of the randomized subjects is similar to a broader insomnia population that has subjective insomnia but that does not meet all eligibility criteria including objective and subjective sleep duration thresholds.
Disclosure of InterestT. Di Marco Employee of: Idorsia Pharmaceuticals Ltd, Y. Dauvilliers Consultant of: Idorsia Pharmaceuticals Ltd, T. Scammell Consultant of: Idorsia Pharmaceuticals Ltd, Neurocrine, Epilog, Roche and Jazz Pharmaceuticals, I. Djonlagic Grant / Research support from: NIH, Consultant of: Idorsia Pharmaceuticals Ltd, UCSD, A. Datta Consultant of: Idorsia Pharmaceuticals Ltd, Neurocrine, Epilog, Roche and Jazz Pharmaceuticals, G. Zammit Grant / Research support from: Idorsia Pharmaceuticals Ltd, Consultant of: Idorsia Pharmaceuticals Ltd, D. Seboek Kinter Employee of: Idorsia Pharmaceuticals Ltd, N. Tjiptarto Grant / Research support from: Idorsia Pharmaceuticals Ltd, J. Donoghue Grant / Research support from: Idorsia Pharmaceuticals Ltd.
The Parkes Pulsar Timing Array third data release
- Andrew Zic, Daniel J. Reardon, Agastya Kapur, George Hobbs, Rami Mandow, Małgorzata Curyło, Ryan M. Shannon, Jacob Askew, Matthew Bailes, N. D. Ramesh Bhat, Andrew Cameron, Zu-Cheng Chen, Shi Dai, Valentina Di Marco, Yi Feng, Matthew Kerr, Atharva Kulkarni, Marcus E. Lower, Rui Luo, Richard N. Manchester, Matthew T. Miles, Rowina S. Nathan, Stefan Osłowski, Axl F. Rogers, Christopher J. Russell, John M. Sarkissian, Mohsen Shamohammadi, Renée Spiewak, Nithyanandan Thyagarajan, Lawrence Toomey, Shuangqiang Wang, Lei Zhang, Songbo Zhang, Xing-Jiang Zhu
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 19 July 2023, e049
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We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.
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.