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Association of an UCP4 (SLC25A27) haplotype with ultra-resistant schizophrenia

    Fayçal Mouaffak

    INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, U894 Centre de Psychiatrie et Neurosciences, Paris, France and Centre Hospitalier Sainte-Anne, CERC, Service Hospitalo-universitaire, 7 rue Cabanis, 75014 Paris, France and Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France

    ,
    Oussama Kebir

    INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, U894 Centre de Psychiatrie et Neurosciences, Paris, France and Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France

    ,
    Alfredo Bellon

    INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, U894 Centre de Psychiatrie et Neurosciences, Paris, France and Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France

    ,
    Raphael Gourevitch

    Centre Hospitalier Sainte-Anne, CERC, Service Hospitalo-universitaire, 7 rue Cabanis, 75014 Paris, France

    ,
    Sylvie Tordjman

    Centre Hospitalier Guillaume Régnier, Service Hospitalo-Universitaire de Psychiatrie de l’Enfant et de l’Adolescent, Rennes, France

    ,
    Annie Viala

    Centre Hospitalier Sainte-Anne, Secteur 13, 1, rue Cabanis, 75014 Paris, France

    ,
    Bruno Millet

    INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, U894 Centre de Psychiatrie et Neurosciences, Paris, France and Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France and Centre Hospitalier Guillaume Régnier, Service Hospitalo-Universitaire de Psychiatrie, CIC, Rennes, France

    ,
    Nematollah Jaafari

    Centre Hospitalier Henri Laborit, Service Hospitalo-Universitaire de Psychiatrie; CIC-P INSERM U 802 Université de médecine et de pharmacie, CHU de Poitiers, 86000 Poitiers, France

    ,
    Jean Pierre Olié

    INSERM, Laboratoire de Physiopathologie des Maladies Psychiatriques, U894 Centre de Psychiatrie et Neurosciences, Paris, France and Centre Hospitalier Sainte-Anne, CERC, Service Hospitalo-universitaire, 7 rue Cabanis, 75014 Paris, France and Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France

    &
    Marie Odile Krebs

    † Author for correspondence

    Centre Hospitalier Sainte-Anne, CERC, Service Hospitalo-universitaire, 7 rue Cabanis, 75014 Paris, France and Université Paris Descartes, Faculté de Médecine Paris Descartes, Paris, France.

    Published Online:https://doi.org/10.2217/pgs.10.179

    Aims: Neuronal uncoupling proteins are involved in the regulation of reactive oxygen species production and intracellular calcium homeostasis, and thus, play a neuroprotective role. In order to explore the potential consequences of neuronal uncoupling proteins variants we examined their association in a sample of Caucasian patients suffering from schizophrenia and phenotyped them according to antipsychotic response. Materials & methods: Using a case–control design, we compared the frequencies of 15 genetic variants spanning UCP2, UCP4 and UCP5 in 106 French Caucasian patients suffering from schizophrenia and 127 healthy controls. In addition, patients with schizophrenia who responded to antipsychotic treatment were compared with patients with ultra-resistant schizophrenia (URS). This latter population presented no clinical, social and/or occupational remission despite at least two periods of treatment with conventional or atypical antipsychotic drugs and also with clozapine. Results: There were no differences in the distribution of the respective alleles between URS and responding patients. However, one haplotype spanning UCP4 was found to be significantly under-represented in URS patients. This relationship remained significant after multiple testing corrections. Conclusion: Although our sample is of limited size and not representative of schizophrenia as a whole, the association found between the URS group and the UCP4 haplotype is noteworthy as it may influence treatment outcome in schizophrenia.

    Original submitted 2nd August 2010; Revision submitted 1st November 2010.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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