2 results
Evidence of an interaction between FXR1 and GSK3β polymorphisms on levels of Negative Symptoms of Schizophrenia and their response to antipsychotics
- Antonio Rampino, Silvia Torretta, Barbara Gelao, Federica Veneziani, Matteo Iacoviello, Aleksandra Marakhovskaya, Rita Masellis, Ileana Andriola, Leonardo Sportelli, Giulio Pergola, Alessandra Minelli, Chiara Magri, Massimo Gennarelli, Antonio Vita, Jean Martin Beaulieu, Alessandro Bertolino, Giuseppe Blasi
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 19 April 2021, e39
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Background
Genome-Wide Association Studies (GWASs) have identified several genes associated with Schizophrenia (SCZ) and exponentially increased knowledge on the genetic basis of the disease. In addition, products of GWAS genes interact with neuronal factors coded by genes lacking association, such that this interaction may confer risk for specific phenotypes of this brain disorder. In this regard, fragile X mental retardation syndrome-related 1 (FXR1) gene has been GWAS associated with SCZ. FXR1 protein is regulated by glycogen synthase kinase-3β (GSK3β), which has been implicated in pathophysiology of SCZ and response to antipsychotics (APs). rs496250 and rs12630592, two eQTLs (Expression Quantitative Trait Loci) of FXR1 and GSK3β, respectively, interact on emotion stability and amygdala/prefrontal cortex activity during emotion processing. These two phenotypes are associated with Negative Symptoms (NSs) of SCZ suggesting that the interaction between these SNPs may also affect NS severity and responsiveness to medication.
MethodsTo test this hypothesis, in two independent samples of patients with SCZ, we investigated rs496250 by rs12630592 interaction on NS severity and response to APs. We also tested a putative link between APs administration and FXR1 expression, as already reported for GSK3β expression.
ResultsWe found that rs496250 and rs12630592 interact on NS severity. We also found evidence suggesting interaction of these polymorphisms also on response to APs. This interaction was not present when looking at positive and general psychopathology scores. Furthermore, chronic olanzapine administration led to a reduction of FXR1 expression in mouse frontal cortex.
DiscussionOur findings suggest that, like GSK3β, FXR1 is affected by APs while shedding new light on the role of the FXR1/GSK3β pathway for NSs of SCZ.
The science of EChO
- Giovanna Tinetti, James Y-K. Cho, Caitlin A. Griffith, Olivier Grasset, Lee Grenfell, Tristan Guillot, Tommi T. Koskinen, Julianne I. Moses, David Pinfield, Jonathan Tennyson, Marcell Tessenyi, Robin Wordsworth, Alan Aylward, Roy van Boekel, Angioletta Coradini, Therese Encrenaz, Ignas Snellen, Maria R. Zapatero-Osorio, Jeroen Bouwman, Vincent Coudé du Foresto, Mercedes Lopez-Morales, Ingo Mueller-Wodarg, Enric Pallé, Franck Selsis, Alessandro Sozzetti, Jean-Philippe Beaulieu, Thomas Henning, Michael Meyer, Giuseppina Micela, Ignasi Ribas, Daphne Stam, Mark Swain, Oliver Krause, Marc Ollivier, Emanuele Pace, Bruce Swinyard, Peter A.R. Ade, Nick Achilleos, Alberto Adriani, Craig B. Agnor, Cristina Afonso, Carlos Allende Prieto, Gaspar Bakos, Robert J. Barber, Michael Barlow, Peter Bernath, Bruno Bézard, Pascal Bordé, Linda R. Brown, Arnaud Cassan, Céline Cavarroc, Angela Ciaravella, Charles Cockell, Athéna Coustenis, Camilla Danielski, Leen Decin, Remco De Kok, Olivier Demangeon, Pieter Deroo, Peter Doel, Pierre Drossart, Leigh N. Fletcher, Matteo Focardi, Francois Forget, Steve Fossey, Pascal Fouqué, James Frith, Marina Galand, Patrick Gaulme, Jonay I. González Hernández, Davide Grassi, Matt J. Griffin, Ulrich Grözinger, Manuel Guedel, Pactrick Guio, Olivier Hainaut, Robert Hargreaves, Peter H. Hauschildt, Kevin Heng, David Heyrovsky, Ricardo Hueso, Pat Irwin, Lisa Kaltenegger, Patrick Kervella, David Kipping, Geza Kovacs, Antonino La Barbera, Helmut Lammer, Emmanuel Lellouch, Giuseppe Leto, Mercedes Lopez Morales, Miguel A. Lopez Valverde, Manuel Lopez-Puertas, Christophe Lovi, Antonio Maggio, Jean-Pierre Maillard, Jesus Maldonado Prado, Jean-Baptiste Marquette, Francisco J. Martin-Torres, Pierre Maxted, Steve Miller, Sergio Molinari, David Montes, Amaya Moro-Martin, Olivier Mousis, Napoléon Nguyen Tuong, Richard Nelson, Glenn S. Orton, Eric Pantin, Enzo Pascale, Stefano Pezzuto, Ennio Poretti, Raman Prinja, Loredana Prisinzano, Jean-Michel Réess, Ansgar Reiners, Benjamin Samuel, Jorge Sanz Forcada, Dimitar Sasselov, Giorgio Savini, Bruno Sicardy, Alan Smith, Lars Stixrude, Giovanni Strazzulla, Gautam Vasisht, Sandrine Vinatier, Serena Viti, Ingo Waldmann, Glenn J. White, Thomas Widemann, Roger Yelle, Yuk Yung, Sergey Yurchenko
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- Journal:
- Proceedings of the International Astronomical Union / Volume 6 / Issue S276 / October 2010
- Published online by Cambridge University Press:
- 10 November 2011, pp. 359-370
- Print publication:
- October 2010
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The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are?
In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life.
The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole.
EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates.