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Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia

The Pharmacogenomics Journal volume 11, pages 267–273 (2011)Cite this article

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Abstract

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case–control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.

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Acknowledgements

We thank all the patients and healthy volunteers involved in this study. The Psydev Team is also composed of Sophie Leroy, Katia Ossian, Narjes Bendjemaa, Françoise Polides, Souhail Bannour and Marie-Josée Dos Santos. This work was supported by Institut National de la Santé et de la Recherche Médicale (Inserm), Centre Hospitalier Sainte Anne Hôpital Sainte-Anne and by the Fondation Pierre Deniker. This study was supported by the Collaborative Network for Family Study in Psychiatry (‘Réseau d’étude familiale en Psychiatry’, REFAPSY), supported by the Fondation Pierre Deniker: Hôpital Sainte-Anne, Paris SHU: MO Krebs; SM,13: Dr MN Vacheron, Dr A Viala; SM,17: Dr F Petitjean, Dr C Launay; SM,:18 Dr B Garnier, Dr B Dageyne; CMME, Paris: Pr J Guelfi, Dr C Even; Centre Hospitalier Spécialisé Les Mureaux : Dr G Naruse, Dr S Abbas, Dr A Anne, Dr T Loucif, Dr T Mouheb, Dr I Bardaune, Dr N Chellali-Gherab, Dr K Nissas, Dr P Cheminant; CH Guillaume Régnier, Rennes: Pr S Tordjman, Pr B Millet, Dr D Levoyer, Dr S Gault; Etablissement Public de Santé Erasme, Anthony: Dr JC Pascal, Dr M Shahidi; CHS Ville Evrard, Saint-Denis: Dr D Januel, Dr G Saba; Dr L Stamatiadis; CHU Strasbourg : Pr JM Danion, Dr A Baratta; Hôpital Sud, Grenoble: Pr T Bougerol, Dr M Polosan; Hôpital Laborit, Poitiers: Pr JL Senon, Dr N Jaafari, Dr S Rousse; CHU Bretonneau, Tours: Dr F Bonnet-Brilhault; Pr C Barthélémy; Fondation Lenval, Nice: Pr F Askenazy, Y Seddiki. We also acknowledge Afsaneh Gray for the English editing of the paper.

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Authors and Affiliations

  1. INSERM U894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Paris, France

    F Mouaffak, O Kebir, M Chayet, B Millet, A Bellon, J P Olié & M-O Krebs

  2. Service Hospitalo Universitaire, Centre Hospitalier Sainte-Anne, Paris, France

    F Mouaffak, M Chayet, J P Olié & M-O Krebs

  3. Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France

    F Mouaffak, O Kebir, B Millet, A Bellon, J P Olié & M-O Krebs

  4. Service Hospitalo-Universitaire de Psychiatrie de l’Enfant et de l’Adolescent CH Guillaume Régnier, Rennes, France

    S Tordjman

  5. Secteur 13, Centre Hospitalier Sainte-Anne, Paris, France

    M N Vacheron

  6. Service Hospitalo-Universitaire de Psychiatrie, CH Guillaume Régnier, Rennes, France

    B Millet

  7. Service Hospitalo-Universitaire de Psychiatrie, CH Henri Laborit, Poitiers, France

    N Jaafari

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  1. F Mouaffak
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Mouaffak, F., Kebir, O., Chayet, M. et al. Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia. Pharmacogenomics J 11, 267–273 (2011). https://doi.org/10.1038/tpj.2010.40

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