Bruno Etain

Publications (55) View all

• Article: [Trouble bipolaire à début précoce : validation par les études de mélange et les biomarqueurs.]

  Pierre Alexis Geoffroy, Bruno Etain, Stéphane Jamain, Frank Bellivier, Marion Leboyer
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  ABSTRACT: Objectifs : Le trouble bipolaire (TB) est une maladie multifactorielle de présentation clinique hétérogène, en particulier au niveau de l'âge de début (ADD). La pertinence d'un tel indicateur a été discutée et il est proposé dans les futures classifications nosographiques. Méthode : Nous avons effectué la synthèse systématique des études de mélange de distributions (ou dites d'admixture) ainsi que les biomarqueurs du TB à début précoce (TBDP). Résultats : Plusieurs arguments cliniques montrent que le TBDP est un sous-groupe cliniquement homogène qui présente des caractéristiques sévères et récurrentes. Huit études de mélange ont démontré l'existence de trois sous-groupes de patients souffrant du TB selon l'ADD (précoce, intermédiaire, et tardif) avec deux valeurs seuils de 21 (21,33 ans [ET 1,41]) et 35 ans (34,67 ans [ET 5,52]). Le sous-groupe du TBDP est caractérisé par : un taux plus élevé de tentatives de suicide, des cycles rapides, des mésusages d'alcool et drogues, des symptômes psychotiques et des comorbidités anxieuses. Des données génétiques, biologiques, d'imagerie et cognitives peuvent être considérées comme étant des marqueurs possibles de validité externe du TBDP. L'ajout de l'ADD dans les algorithmes de décision thérapeutique pourrait être intéressant même si le niveau de preuve est à consolider. Conclusion : La fréquence importante du TBDP (44,80 %) devrait pousser les cliniciens à une plus grande vigilance afin qu'ils apportent des stratégies préventives, un diagnostic et un traitement précoce à ces patients au tableau clinique particulièrement sévère. Cette pertinence clinique fait que le prochain DSM-5 devrait inclure l'ADD en tant que caractéristique du TB.
  Canadian journal of psychiatry. Revue canadienne de psychiatrie 04/2013; 58(4):240-248. · 2.42 Impact Factor
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  Available from: Pierre Alexis Geoffroy

  Article: Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset.

  Pierre Alexis Geoffroy, Bruno Etain, Jan Scott, Chantal Henry, Stéphane Jamain, Marion Leboyer, Frank Bellivier
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  ABSTRACT: Bipolar disorder is a multifactorial psychiatric disorder with developmental and progressive neurophysiological alterations. This disorder is typically characterized by cyclical and recurrent episodes of mania and depression but is heterogeneous in its clinical presentation and outcome. Although the DSM-IV-TR criteria identify several features that are of phenomenological relevance, these are of less utility for defining homogeneous subgroups, for analyses of correlations with biomarkers or for directing focused medication strategies. We provide a comprehensive review of existing evidence regarding to age at onset in bipolar disorder. Eight admixture studies demonstrate three homogeneous subgroups of patients with bipolar disorder identified according to age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years. It is suggested that the early-onset subgroup has specific clinical features and outcomes different from those of the other subgroups. Early-onset subgroup may be considered a more suitable clinical phenotype for the identification of susceptibility genes with recent data demonstrating associations with genetic variants specifically in this subgroup. The use of age at onset as a specifier may also facilitate the identification of other biological markers for use in brain imaging, circadian, inflammatory and cognitive research. A key challenge is posed by the use of age at onset in treatment decision algorithms, although further research is required to increase the evidence-base. We discuss three potential benefits of specifying age at onset, namely: focused medication strategies, the targeted prevention of specific comorbid conditions and decreasing the duration of untreated illness. We argue that age at onset should be included as a specifier for bipolar disorders.
  Journal of Physiology-Paris 03/2013; · 1.31 Impact Factor
• Article: The HLA-G low expressor genotype is associated with protection against Bipolar Disorder.

  Monojit Debnath, Marc Busson, Stéphane Jamain, Bruno Etain, Nora Hamdani, José Oliveira, Wahid Boukouaci, Kahina Amokrane, Hélène Moins-Teisserenc, Mohamed Lajnef, Djaouida Bengoufa, Alain Malafosse, Frank Bellivier, Chantal Henry, Jean-Pierre Kahn, Rajagopal Krishnamoorthy, Dominique Charron, Marion Leboyer, Ryad Tamouza
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  ABSTRACT: Implication of immune processes in bipolar disorder (BD) has recently gained increasing attention. Tolerogenic molecules, among which HLA-G plays a prominent role, mediate the modulation of such processes. The HLA-G locus is characterized by a high number of polymorphisms including a functionally relevant 14 base pair (bp) insertion/deletion (Ins/Del) allele affecting the HLA-G expression. Here, we analyzed the distribution of this polymorphism in 561 BD patients and 161 healthy and found that the HLA-G 14bp Ins/Ins genotype was significantly more prevalent in healthy controls than in patients (corrected p; pc = 0.032) and that the prevalence of such protective genotype is lower among patients born during the winter season as compared to those born in other periods (pc = 0.006). Possible mechanisms between low HLA G expression and resistance to infections as well as potential relationships between infections in early life and susceptibility to BD are discussed.
  Human immunology 12/2012; · 2.55 Impact Factor
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  Available from: Pierre Alexis Geoffroy

  Article: Combination Therapy for Manic Phases: A Critical Review of a Common Practice.

  Pierre Alexis Geoffroy, Bruno Etain, Chantal Henry, Frank Bellivier
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  ABSTRACT: All relevant guidelines recommend monotherapy as the initial treatment for manic phases of bipolar disorder (BD), with combination therapy reserved for severe cases or as a subsequent choice. However, in routine practice, monotherapy is often not sufficiently effective for acute and/or maintenance therapy. As a consequence, most patients are given combination therapies. An extensive search concerning combination treatment for manic episodes was conducted for relevant international randomized controlled studies, treatment guidelines and comprehensive reviews published since 1980. The scientific literature is sufficiently rich to validate the superiority of combination therapy over monotherapy in the manic phase in terms of efficacy and prevention of relapse; its safety profile is acceptable. Side effects are more frequent with combination therapy as a whole than with monotherapy, and discontinuation rates due to adverse events are higher. Continued administration of antipsychotics after a manic phase is controversial: drug classification, the course of the disease and the predominant polarity should all be considered before treatment is continued. Combinations including olanzapine and asenapine and to a lesser extent risperidone are associated with weight gain, those including quetiapine, haloperidol and asenapine with sedation, and those including aripiprazole with akathisia. This review of literature leads us to suggest that combination therapy including an atypical antipsychotic with lithium or valproate may be considered as a first-line approach. An appropriate algorithm for making decisions about combination treatment needs to be developed and included in future guidelines.
  CNS Neuroscience & Therapeutics 10/2012; · 4.44 Impact Factor
• Article: Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder.

  Bruno Etain, Anne Dumaine, Frank Bellivier, Cécile Pagan, Laetitia Francelle, Hany Goubran-Botros, Sarah Moreno, Jasmine Deshommes, Khaled Moustafa, Katia Le Dudal, Flavie Mathieu, Chantal Henry, Jean-Pierre Kahn, Jean-Marie Launay, Thomas W Mühleisen, Sven Cichon, Thomas Bourgeron, Marion Leboyer, Stéphane Jamain
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  ABSTRACT: Patients affected by bipolar disorder (BD) frequently report abnormalities in sleep/wake cycles. In addition, they showed abnormal oscillating melatonin secretion, a key regulator of circadian rhythms and sleep patterns. The acetylserotonin O-methyltransferase (ASMT) is a key enzyme of the melatonin biosynthesis and has recently been associated with psychiatric disorders such as autism spectrum disorders and depression. In this paper, we analysed rare and common variants of ASMT in patients with BD and unaffected control subjects and performed functional analysis of these variants by assaying the ASMT activity in their B-lymphoblastoid cell lines. We sequenced the coding and the regulatory regions of the gene in a discovery sample of 345 patients with BD and 220 controls. We performed an association study on this discovery sample using common variants located in the promoter region and showed that rs4446909 was significantly associated with BD (P= 0.01) and associated with a lower mRNA level (P< 10(-4)) and a lower enzymatic activity (P< 0.05) of ASMT. A replication study and a meta-analysis using 480 independent patients with BD and 672 controls confirmed the significant association between rs4446909 and BD (P= 0.002). These results correlate with the general lower ASMT enzymatic activity observed in patients with BD (P= 0.001) compared with controls. Finally, several deleterious ASMT mutations identified in patients were associated with low ASMT activity (P= 0.01). In this study, we determined how rare and common variations in ASMT might play a role in BD vulnerability and suggest a general role of melatonin as susceptibility factor for BD.
  Human Molecular Genetics 06/2012; 21(18):4030-7. · 7.64 Impact Factor