M C Mouren-Simeoni

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (106)184.97 Total impact

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    ABSTRACT: Autism spectrum disorders (ASD) are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2. The analysis of rare variations of 8 candidate genes among the 27 genes located in this region suggested SEZ6L2 as a compelling candidate. We further explored the role of SEZ6L2 variations by screening its coding part in a group of 452 individuals, including 170 patients with ASD and 282 individuals from different ethnic backgrounds of the Human Genome Diversity Panel (HGDP), complementing the previously reported screening. We detected 7 previously unidentified non-synonymous variations of SEZ6L2 in ASD patients. We also identified 6 non-synonymous variations present only in HGDP. When we merged our results with the previously published, no enrichment of non-synonymous variation in SEZ6L2 was observed in the ASD group compared with controls. Our results provide an extensive ascertainment of the genetic variability of SEZ6L2 in human populations and do not support a major role for SEZ6L2 sequence variations in the susceptibility to ASD.
    PLoS ONE 01/2011; 6(3):e17289. · 3.53 Impact Factor
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    ABSTRACT: Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.
    PLoS ONE 01/2010; 5(7):e11495. · 3.53 Impact Factor
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    Richard Delorme, Pauline Chaste, Marie Christine Mouren-Simeoni, Marion Leboyer
    Journal of the American Academy of Child and Adolescent Psychiatry 06/2009; 48(5):573; author reply 573-4. · 6.97 Impact Factor
  • E. Excoffier, G. Vila, E. Taupiac, M.-C. Mouren-Simeoni, M.-P. Bouvard
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    ABSTRACT: Social deficit is the core symptom of pervasive developmental disorder. In other child psychiatric disorders, social problems are also described but mainly as a result of the disease symptomatology. However, some recent studies suspect that in several disorders such as attention deficit hyperactive disorder, patients have an endogenous social disturbance. The aim of our research was to study abnormal child social behaviour in several disorders, using a dimensional approach. It is a preliminary validation study of the French version of the Children's Social Behaviour Questionnaire, a dimensional instrument constructed by Luteijn, Minderaa et al. Methodology Five clinical groups, according to the DSM IV criteria, formed a population of 103 children aged 6 to 16 years old : autistic disorder, attention deficit hyperactive disorder (ADHD), emotional disorder (anxious, depressed), mental retardation and normal children. Parents completed the Child Behaviour Checklist (CBCL) and the Children's Social Behaviour Questionnaire (CSBQ). The research worker and the child's physician completed a data form. The data form included information about medical history, development and socio-demographic criteria. The CBCL explored children's behaviours and general psychopathology, and included social dimensions (withdrawn, social problems, aggressive/delinquent behaviours, thought problems). The CSBQ, a dimensional questionnaire, explored children's social behaviours and included five dimensions : « acting-out », « social contact », « social insight », « social anxiety », « social stereotypes ». The English version of the CSBQ, validated with in the Netherlands Dutch population was translated into French and the translation was validated (double back translation). As the CBCL and CSBQ questionnaires are both dimensional instruments, dimensions have been compared. All instrument results were analysed separately ; correlations and comparisons were made between groups. Results Correlations between CSBQ and CBCL dimensions are consistent. Positive correlations exist for : « acting-out » dimension with « external behaviours », « aggressive behaviour » and « delinquent behaviour » ; « social contact » with « internal behaviours » and « withdrawn » ; « social Insight » with « social problems » and « attention problems » ; « social anxiety » with « anxious/depressed », « thought problems » and « internal behaviours » ; social stereotypes » with « thought problems ». Mean CSBQ results are as follows : 1. autistic group has the highest score for the « social contact » dimension, ADHD group has the highest score for the « acting-out » dimension, mental retardation group has the highest score for the « social insight » dimension. 2. comparisons between groups shows : significant difference between the autistic and ADHD groups for « social contact » and « social anxiety » but not for « social insight » and « acting-out » ; between the autistic and mental retardation groups, there is a significant difference for « social contact » but not for the other dimensions ; between the ADHD and mental retardation groups, there is a significant difference only for « acting-out » ; there is no significant difference between the ADHD and emotional groups ; control group has very low scores. CBCL results are : abnormal scores in all groups except normal control group, for « social problems » and « attention problems » ; abnormal scores in the autistic and emotional groups for « anxious/depressed », « withdrawn » and « internal behaviours » ; abnormal scores in the ADHD group for « aggressive behaviour », « delinquent behaviour » and « external behaviours » ; the « internal behaviours » score is borderline. Discussion Social behaviour profiles are different and characteristic for each disorder. However, social symptoms are not specific for one disorder and common social signs do exist between different disorders. Our results are concordant with the Luteijn study and literature data. The results support the hypothesis of a dimensional pathogenesis in social behaviour disturbance. We discuss the benefit of a dimensional approach to complete the categorical one. The Children's Social Behaviour Questionnaire seems to be an interesting instrument to explore social behaviour disturbances in several child disorders.
    Encephale-revue De Psychiatrie Clinique Biologique Et Therapeutique - ENCEPHALE. 01/2007; 33(4):585-591.
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    ABSTRACT: Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed. This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years). We report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another. These findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach.
    BMC Psychiatry 02/2006; 6:1. · 2.23 Impact Factor
  • G. Michel, D. Purper-Ouakil, M.-C. Mouren-Simeoni
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    ABSTRACT: Risk taking behaviour, which starts and develops during adolescence, now constitues a public health problems. The use of toxins, road accidents, high-risk sports, etc, are responsible, in the long-term, for considerable morbidity and mortality. After defining risk and risk taking behaviour we'll analyse in a developpemental approach the role of these behaviours during adolescence. We'll analyse the psychological vulnerability factors in risk taking behavior (behaviour factors, psychoenvironnemental factors, psychopathological factors, personality factors and self-evaluation capacities). In this article we were interested principally at four risk taking behaviours: a) risky sexual behaviour; b) high-risk sports; c) dangerous moped driving; d) psychoactive substance use. In the discussion, we'll focus on the heuristic and preventive approaches of risk taking behaviour during adolescence.
    Neuropsychiatrie de l'Enfance et de l'Adolescence. 01/2006; 54(1):62-76.
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    ABSTRACT: Age at onset (AAO) has been useful to explore the clinical, neurobiological and genetic heterogeneity of obsessive-compulsive disorder (OCD). However, none of the various thresholds of AAO used in previous studies have been validated, and it remains an unproven notion that AAO is a marker for different subtypes of OCD. If AAO is a clinical indicator of different biological subtypes, then subgroups based on distinct AAOs should have separate normal distributions as well as different clinical characteristics. Admixture analysis was used to determine the best-fitting model for the observed AAO of 161 OCD patients. The observed distribution of AAO in OCD is a mixture of two Gaussian distributions with mean ages of 11.1 +/- 4.1 and 23.5 +/- 11.1 years. The first distribution, defined by early-onset OCD, had increased frequency of Tourette's syndrome and increased family history of OCD. The second distribution, defined by late-onset OCD, showed elevated prevalence of general anxiety disorder and major depressive disorder. These results, based on a statistically validated AAO cut-off and those of previous studies on AAO in OCD, suggest that AAO is a crucial phenotypic characteristic in understanding the genetic basis of this disorder.
    Psychological Medicine 03/2005; 35(2):237-43. · 5.59 Impact Factor
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    ABSTRACT: In obsessive-compulsive disorder (OCD), clinical, neurobiological and genetic differences have been reported according to age at onset (AAO). Given the importance of identifying homogeneous subtypes in complex heterogeneous disorders such as OCD, it would be particularly useful to identify a specific cognitive profile associated with early-onset OCD. Although impaired cognition has repeatedly been demonstrated in OCD patients, discrepancies between studies have hampered the identification of a precise cognitive dysfunction. Executive dysfunction has often been reported, but findings have not always been replicated. The aim of this study was to assess executive functions in 30 patients according to their AAO. The sample consisted of 15 early-onset and 15 late-onset OCD patients and 22 normal controls, matched for age, sex and socio-economic status. Various aspects of executive function were assessed with five neuropsychological tests : Tower of London, Trail Making Test, Verbal Fluency, Design Fluency and Association Fluency. The 30 OCD patients obtained lower total scores than the controls in the Tower of London test and association fluency task (p < 0.05 and p < 0.001, respectively). Impairments were more marked for the earlyonset group, with no effect of gender or age at interview. Deficits in specific aspects of frontal lobe function were found in the OCD group and were particularly pronounced within the earlyonset group. These findings confirm clinical data suggesting that OCD patients can be subtyped according to age at onset and that OCD patients present unusual cognitive characteristics. They also support the hypothesis that earlyonset OCD might be a relevant subgroup characterised both by a particular clinical profile and by specific cognitive characteristics.
    Encephale-revue De Psychiatrie Clinique Biologique Et Therapeutique - ENCEPHALE. 01/2005; 31(6):666-671.
  • G Michel, M F Le Heuzey, D Purper-Ouakil, M C Mouren-Siméoni
    Revue de l'infirmière 07/2004;
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    ABSTRACT: - To study the types of psychiatric problem encountered in children infected with the human immunodeficiency virus (HIV) and their relationship to central nervous system disorder and the severity of infection. - 17 HIV-infected children presenting with psychiatric problems were included. Mental disorders were evaluated according to DSM-IV criteria. Neurological disorders and progressive encephalopathy (presence or absence) diagnosis were evaluated by clinical and radiological examination. The severity of infection was assessed by the percentage of CD4 lymphocytes. - The most frequent diagnoses were major depression (MDD: 47%) and attention deficit hyperactivity disorder (ADHD: 29%). Major depression diagnosis was significantly associated with neuroimaging or clinical neurological abnormalities (p < 0.01). In contrast, no association was found between hyperactivity diagnosed according to DSM-IV criteria and central nervous system disorder. Percentage of CD4 lymphocytes were close to 0 for more than 80% of children presenting with psychiatric complications. - The very low % of CD4 lymphocytes of these children suggest that the appearance of a psychiatric complication should be regarded as a factor indicating severe HIV infection. Depressive disorders may be a clinical form of encephalopathy.
    European Psychiatry 06/2004; 19(3):182-4. · 3.29 Impact Factor
  • F Ducuing, M F LeHeuzey, V Rouyer, M C Mouren-Simeoni
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    ABSTRACT: Continuous spikes and waves during slow wave sleep syndrome (CSWS) is a seldom form of epilepsy which may manifest by neurocognitive and/or psychiatric abnormalities, with or without clinical seizures. CASE REPORT: A 5-year-old child was presented with a language disorder and behaviour abnormalities. A standard electroencephalograph (EEG) showed left tempororolandic spikes waves without any electrical discharges. Cerebral imaging excluded an underlying expansive disease. A continuous EEG recording revealed a CSWS syndrome by showing continuous and diffuse spike waves during slow wave sleep. Thanks to antiepileptic medications and orthophonic therapy, evolution was positive. CONCLUSION: In complex cases of language and behavioural disorders, it is necessary to perform an EEG even in the absence of convulsive seizures, to diagnose a CSWS syndrome. Given the etiological and treatment difficulties concerning the CSWS, a treatment with antiepileptic seems necessary. EEG normalisation under antiepileptic medications usually leads to significant, although partial, neuropsychological improvement. Furthermore, orthophonic therapy seems useful as a complement to pharmacological treatment.
    Archives de Pédiatrie 05/2004; 11(4):347-9. · 0.36 Impact Factor
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    ABSTRACT: Several lines of evidence suggest that obsessive compulsive disorder (OCD) could be the consequence of glutamatergic dysfunction. We performed a case-control study in 156 patients and 141 controls and the transmission disequilibrium test in 124 parent-offspring trios to search for association between OCD and two kainate receptors, GRIK2 and GRIK3. Using three single nucleotide polymorphisms (SNP) in GRIK2 and one in GRIK3, we found no evidence for association in case-control or family-based analyses. Only the GRIK2 SNP I867, recently associated with autism, was less transmitted than expected (p < 0.03), supporting a functional role for this variant. These findings suggest the need for further investigation of the role of GRIK2 in OCD.
    Neuroreport 03/2004; 15(4):699-702. · 1.40 Impact Factor
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    ABSTRACT: To evaluate the type and frequency of psychiatric disorders in obese children and adolescents; to assess the correlation between psychopathology and severity of obesity; to explore the relationship between psychiatric disorders in obese children and obesity and psychopathology in their parents. One hundred fifty-five children referred and followed for obesity were evaluated (98 girls and 57 boys; age, 5 to 17 years). Psychiatric disorders were assessed through a standardized diagnostic interview schedule (K-SADS R) and self-report questionnaires completed by the child (STAIC Trait-anxiety and CDI for depression) or his (her) parents (CBCL or GHQ). These obese children were compared with insulin-dependent diabetic (IDDM) outpatient children (N = 171) on questionnaire data. Eighty-eight obese children obtained a DSM-IV diagnosis, most often an anxiety disorder (N = 63). Psychological disorders were particularly pronounced in those obese children whose parents were disturbed. There was no correlation between severity of obesity in the child or his (her) parents and frequency of psychiatric disorders. Compared with diabetic children, they displayed significantly higher internalized and externalized questionnaire scores and poorer social skills. These results highlight the importance of including a child psychiatric component in the treatment of obesity, which must engage the whole family.
    Psychosomatic Medicine 01/2004; 66(3):387-94. · 4.08 Impact Factor
  • F Ducuing, M. F LeHeuzey, V Rouyer, M. C Mouren-Simeoni
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    ABSTRACT: Continuous spikes and waves during slow wave sleep syndrome (CSWS) is a seldom form of epilepsy which may manifest by neurocognitive and/or psychiatric abnormalities, with or without clinical seizures.Case report. – A 5-year-old child was presented with a language disorder and behaviour abnormalities. A standard electroencephalograph (EEG) showed left tempororolandic spikes waves without any electrical discharges. Cerebral imaging excluded an underlying expansive disease. A continuous EEG recording revealed a CSWS syndrome by showing continuous and diffuse spike waves during slow wave sleep. Thanks to antiepileptic medications and orthophonic therapy, evolution was positive.Conclusion. – In complex cases of language and behavioural disorders, it is necessary to perform an EEG even in the absence of convulsive seizures, to diagnose a CSWS syndrome. Given the etiological and treatment difficulties concerning the CSWS, a treatment with antiepileptic seems necessary. EEG normalisation under antiepileptic medications usually leads to significant, although partial, neuropsychological improvement. Furthermore, orthophonic therapy seems useful as a complement to pharmacological treatment.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2004; 11(4):347-349.
  • S. Renou, T. Hergueta, M. Flament, M.-C. Mouren-Simeoni, Y. Lecrubier
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    ABSTRACT: Les entretiens diagnostiques structurés, qui se sont développés parallèlement aux systèmes de classification en psychiatrie, sont maintenant largement utilisés en recherche et en pratique clinique chez l’adulte. Ils présentent de nombreux avantages en permettant d’évaluer de manière standardisée les troubles et les comorbidités, d’explorer leurs durées, leurs fluctuations symptomatiques et leurs évolutions. Chez l’enfant et l’adolescent, la recherche en pharmacologie et en épidémiologie a beaucoup augmenté ces dernières années et la standardisation des procédures diagnostiques devient un problème crucial dans ces 2 domaines. Cet article a pour objectif de recenser et de décrire les outils standardisés d’aide au diagnostic psychiatrique disponibles actuellement chez l’enfant et l’adolescent. Le choix a été effectué, après revue exhaustive des bases documentaires Medline et PsycINFO, sur 4 critères principaux : la compatibilité avec les systèmes de classifications internationales (DSM IV et/ou CIM-10), le nombre de troubles évalués, les publications dans des revues à comité de lecture et les qualités métrologiques. Après analyse de l’information recueillie, 2 entretiens diagnostiques structurés [le Diagnostic Interview Schedule for Children (DISC) et le Children's Interview for Psychiatric Syndromes (ChIPS)] et 4 entretiens semi-structurés &lsqb;le Schedule for affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS), le Diagnostic Interview for Children and Adolescent (DICA), le Child and Adolescent Psychiatric Assessment (CAPA) et l’Interview Schedule for Children and Adolescents (ISCA)[ ont pu être retenus selon nos 2 premiers critères. Pour ce qui concerne le critère relatif aux qualités métrologiques, le choix a été plus difficile tant les données sont parcellaires et portent sur des échantillons faibles. Néanmoins, il apparaît que la fidélité interjuges, généralement bonne pour ce type d’instrument, est satisfaisante avec des kappa variant de 0,5 à 1,0, et que la fidélité test-retest peut être tout à fait médiocre mais aussi excellente en fonction des instruments, du statut de « l’informant » (parent et/ou enfant) et du trouble évalué, les kappa variant de 0,32 à 1. Les études de validité montrent des concordances diagnostiques faibles à modérées. Deux autres points importants ressortent de ce travail. La durée des entretiens, comme pour la plupart des instruments existant chez l’adulte, est trop longue d’autant que les entretiens doivent être faits le plus souvent chez l’enfant ou l’adolescent et chez un adulte référent. Par ailleurs, ces instruments n’existent pour la plupart qu’en anglais, ce qui ne favorise pas les échanges et les études multinationales. À titre d’exemple, seul le Kiddie-SADS est actuellement disponible en français. Il paraît nécessaire de poursuivre le développement des entretiens diagnostiques structurés chez l’enfant et l’adolescent en accentuant leur simplification et en améliorant leurs qualités métrologiques. Ces travaux sont longs, coûteux et parfois fastidieux mais constituent un passage obligé pour asseoir les recherches en pédopsychopathologie sur de bonnes bases.
    Encephale-revue De Psychiatrie Clinique Biologique Et Therapeutique - ENCEPHALE. 01/2004; 30(2):122-134.
  • P. Isnard, M. Frelut, G. Michel, J. Cezard, M. Mouren-Simeoni
    Journal of Pediatric Gastroenterology and Nutrition - J PEDIAT GASTROENTEROL NUTR. 01/2004; 39.
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    ABSTRACT: To assess the prevalence of alexithymia in insulin-dependent diabetic mellitus (IDDM) outpatients. To examine whether alexithymia is associated with diabetic somatic variables, depression, and compliance. Our sample comprised 69 diabetic outpatients followed in a university hospital. We assessed the prevalence of alexithymia (26-item Toronto Alexithymia Scale, TAS-26) and the relationships among alexithymia, depression (13-item Beck Depression Inventory, BDI-13), somatic diabetic variables (glycosylated hemoglobin, number of mild or severe hypoglycemia, somatic complications), and compliance (observer-rater scale completed by diabetologist). The prevalence of alexithymia in IDDM patients was low (14.4%). Alexithymia and depression, as measured by TAS-26 and BDI-13 scores, respectively, correlated with each other. Alexithymia was not correlated with glycemic control, somatic complications, or compliance. In our sample, alexithymia was related to depression and not to somatic factors or compliance.
    Journal of Psychosomatic Research 10/2003; 55(3):285-7. · 3.27 Impact Factor
  • Michel G, Purper-Ouakil D, Leheuzey M.F, Mouren-Siméoni M.C
    Alcoologie et Addictologie. 01/2003;
  • G Michel, D Purper-Ouakil, M. F Leheuzey, M. C Mouren-Simeoni
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    ABSTRACT: Even though it took various forms, sports practice remains considered as necessary in child and adolescent development in a physical and psychological perspective: socializing function in team sports, cathartic function of physical exercise. Risk’s associated with sports practice are most often analysed in terms of accident prevalence rather than in terms of psychopathology. This article aims to review the mains psychopathological risks associated to sports practice in child and adolescent. We shall review overstraining syndrome, eating disorders, doping, and relations between sports and dependence. We shall discuss detection, prevention and potential therapeutic leads in the field of sports psychopathology of child and adolescent.
    Neuropsychiatrie De L'enfance Et De L'adolescence. 01/2003; 51(4):179-185.
  • G. Michel, D. Purper-Ouakil, M.F. Leheuzey, M.C. Mouren-Simeoni
    Neuropsychiatrie de l Enfance et de l Adolescence 01/2003; 51(4).

Publication Stats

1k Citations
184.97 Total Impact Points

Institutions

  • 2005–2011
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009
    • Hôpital Albert Chenevier – Hôpitaux Universitaires Henri Mondor
      Créteil, Île-de-France, France
  • 1990–2007
    • Hôpital Universitaire Robert Debré
      • Service de Psychiatrie de l'Enfant et de l'Adolescent
      Lutetia Parisorum, Île-de-France, France
  • 2002–2006
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2001–2004
    • University of Tours
      Tours, Centre, France
  • 1998–2003
    • Centre Hospitalier Sainte Anne
      Lutetia Parisorum, Île-de-France, France
  • 2000
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • University of Bordeaux
      Burdeos, Aquitaine, France
    • Centre de Pneumologie et d'Allergologie
      Avinyó, Provence-Alpes-Côte d'Azur, France