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1. Relationships between cognition, functioning, and quality of life of euthymic patients with bipolar disorder: Structural equation modeling with the FACE-BD cohort

Author

P Roux, S Frileux, N Vidal, V Aubin, R Belzeaux, P Courtet, C Dubertret, B Etain, E Haffen, M Leboyer, A Lefrere, PM Llorca, K M’Bailara, E Marlinge, E Olié, M Polosan, R Schwan, The FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders) group, E Brunet-Gouet, and C Passerieux

Subjects
antipsychotic, anxiety, bipolar disorders, cognition, depression, psychosis, quality of life, Psychiatry, RC435-571
Abstract

Abstract Background Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning. Methods This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features. Results We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p

Published
2024
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2. Cognitive impairments in treatment-resistant depression: Results from the French cohort of outpatients (FACE-DR)

Author

A Vancappel, Y Dansou, O Godin, E Haffen, A Yrondi, F Stéphan, R Richieri, F Molière, M Horn, E Allauze, JB Genty, A Bouvard, JM Dorey, M Meyrel, V Camus, G Fond, B Péran, M Walter, L Anguill, C Scotto d'Apollonia, AS Nguon, B Fredembach, J Holtzmann, E Vilà, J Petrucci, Rey, B Etain, M Carminati, P Courtet, G Vaiva, PM Llorca, M Leboyer, B Aouizerate, D Bennabi, and W El-Hage

Subjects
Treatment resistant depression, Cognitive impairments, Neuropsychology, Memory, Executive function, Processing speed, Mental healing, RZ400-408
Abstract

Introduction: Previous studies set out cognitive impairments in major depression. However, only two studies were performed among patients suffering from treatment-resistant depression (TRD) and conducted on limited sample sizes. Here, we aimed to characterize cognitive impairments in TRD, and their association with the severity of depression and daily functioning. Method: We included 288 patients suffering from TRD (178 women, 52.5 ± 13.1 years old). They undertook sociodemographic, clinical, daily functioning and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16). We compared our patients’ performances to theoretical performances of the general population. Results: TRD was associated with poorer neuropsychological performances, except for similarities task. We found an effect of depression severity on processing speed and memory, and an impact on daily functioning affecting memory, selective attention and executive function. Conclusion: Patients suffering from TRD have significant cognitive impairments. Therapeutic interventions should be developed to manage such impairments.

Published
2021
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3. A conceptual framework to develop a patient-reported experience measure of the quality of mental health care: a qualitative study of the PREMIUM project in France

Author

S Fernandes, G Fond, X Zendjidjian, P Michel, C Lançon, F Berna, F Schurhoff, B Aouizerate, C Henry, B Etain, L Samalin, M Leboyer, D Misdrahi, PM Llorca, M Coldefy, P Auquier, K Baumstarck, and L Boyer

Subjects
patient-reported experience measures, patient experience, health services research, quality of care, psychiatry, schizophrenia, bipolar disorder, major depressive disorder, severe mental illness, qualitative research, Public aspects of medicine, RA1-1270, Business, HF5001-6182
Abstract

Background: The objective of this study was to develop a conceptual framework to define a domain map describing the experience of patients with severe mental illnesses (SMIs) on the quality of mental health care. Methods: This study used an exploratory qualitative approach to examine the subjective experience of adult patients (18–65 years old) with SMIs, including schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Participants were selected using a purposeful sampling method. Semistructured interviews were conducted with 37 psychiatric inpatients and outpatients recruited from the largest public hospital in southeastern France. Transcripts were subjected to an inductive analysis by using two complementary approaches (thematic analysis and computerized text analysis) to identify themes and subthemes. Results: Our analysis generated a conceptual model composed of 7 main themes, ranked from most important to least important as follows: interpersonal relationships, care environment, drug therapy, access and care coordination, respect and dignity, information and psychological care. The interpersonal relationships theme was divided into 3 subthemes: patient-staff relationships, relations with other patients and involvement of family and friends. All themes were spontaneously raised by respondents. Conclusion: This work provides a conceptual framework that will inform the subsequent development of a patient-reported experience measure to monitor and improve the performance of the mental health care system in France. The findings showed that patients with SMIs place an emphasis on the interpersonal component, which is one of the important predictors of therapeutic alliance. Trial registration: NCT02491866

Published
2021
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4. Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

Author

Marianne Foiselle, Susana Barbosa, Ophélia Godin, Ching-Lien Wu, Wahid Boukouaci, Myrtille Andre, Bruno Aouizerate, Fabrice Berna, Caroline Barau, Delphine Capdevielle, Pierre Vidailhet, Isabelle Chereau, Laetitia Davidovic, Jean-Michel Dorey, Caroline Dubertret, Julien Dubreucq, Catherine Faget, Guillaume Fond, Sylvain Leigner, Pierre-Michel Llorca, Jasmina Mallet, David Misdrahi, Emanuela Martinuzzi, Christine Passerieux, Romain Rey, Baptiste Pignon, Mathieu Urbach, Franck Schürhoff, Nicolas Glaichenhaus, Marion Leboyer, Ryad Tamouza, F. Berna, E. Haffen, M. Leboyer, P.M. Llorca, F. Schürhoff, V. Barteau, S. Bensalem, O. Godin, H. Laouamri, K. Souryis, I. Offerlin-Meyer, B. Pignon, A. Szöke, B. Aouizerate, A. Deloge, D. Misdrahi, E. Vilà, O. Blanc, I. Chéreau, H. Denizot, R.M. Honciuc, D. Lacelle, S. Pires, C. Dubertret, J. Mallet, C. Portalier, J. Dubreucq, C. Fluttaz, F. Gabayet, C. Roman, G. Chesnoy-Servanin, T. D'Amato, J.M. Dorey, R. Rey, A. Vehier, C. Lançon, C. Faget, E. Metairie, P. Peri, F. Vaillant, L. Boyer, G. Fond, P. Vidailhet, A. Zinetti-Bertschy, D. Capdevielle, H. Yazbek, S. Esselin, M. Jarroir, C. Passerieux, and M. Urbach

Subjects
Metabolic syndrome, Schizophrenia, Psychosis, Inflammation, Machine learning, Precision medicine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.

Published
2022
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5. Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental

Author

D. Bennabi, T. Charpeaud, A. Yrondi, J.-B. Genty, S. Destouches, S. Lancrenon, N. Alaïli, F. Bellivier, T. Bougerol, V. Camus, J.-M. Dorey, O. Doumy, F. Haesebaert, J. Holtzmann, C. Lançon, M. Lefebvre, F. Moliere, I. Nieto, C. Rabu, R. Richieri, L. Schmitt, F. Stephan, G. Vaiva, M. Walter, M. Leboyer, W. El-Hage, P.-M. Llorca, P. Courtet, B. Aouizerate, and E. Haffen

Subjects
Treatment resistant depression, Antidepressants, Expert consensus guidelines, Pharmacotherapy, Major depressive disorder, Psychiatry, RC435-571
Abstract

Abstract Background Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. Method Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians’ opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. Results The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. Conclusion The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Published
2019
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6. Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental)

Author

D. Bennabi, A. Yrondi, T. Charpeaud, J.-B. Genty, S. Destouches, S. Lancrenon, N. Allaili, F. Bellivier, T. Bougerol, V. Camus, O. Doumy, J.-M. Dorey, F. Haesebaert, J. Holtzmann, C. Lançon, M. Lefebvre, F. Moliere, I. Nieto, C. Rabu, R. Richieri, L. Schmitt, F. Stephan, G. Vaiva, M. Walter, M. Leboyer, W. El-Hage, B. Aouizerate, E. Haffen, P.-M. Llorca, and P. Courtet

Subjects
Major depressive disorder, Anxiety disorders, Substance use disorders, Elderly, Pharmacotherapy, Psychiatry, RC435-571
Abstract

Abstract Background Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. Method The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. Results The expert guidelines combine scientific evidence and expert clinician’s opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. Conclusion These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Published
2019
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7. Synergistic effects of Lacticaseibacillus rhamnosus GG, glutamine, and curcumin on chronic unpredictable mild stress-induced depression in a mouse model

Author

P. Faucher, A. Dries, P.Y. Mousset, M. Leboyer, J. Dore, and D. Beracochea

Subjects
Microbiology (medical), Microbiology
Abstract

The microbiota-gut-brain axis is important in anxiety-depressive disorders. These conditions are associated with dysbiosis of the intestinal microbiota, intestinal hyperpermeability and an increase in circulating markers of inflammation and oxidative stress. They are also associated with a deregulation of the glutamine-glutamate-γ-aminobutyric acid cycle, with impairment of the excitatory/inhibitory balance in the brain. Our aim was to examine the impact of chronic treatment with the probiotic organism Lacticaseibacillus rhamnosus GG, alone or in combination with glutamine and curcumin, in a validated model of anxiety-depressive disorder in mice. Six-month-old mice (n=144) were exposed to chronic unpredictable mild stress (CUMS) stimulation for 3 weeks and emotional disturbances were assessed using two tests assessing anxiety (elevated plus maze test) and depressive-like behaviour (tail suspension test). After discontinuation of CUMS, mice were force-fed once-daily with curcumin, glutamine and probiotic alone or in combination for 21 consecutive days. Emotional reactivity was assessed in two separate behavioural tests: open field test and forced swim test. The outcomes of the interventions were compared with those induced by acute intraperitoneal administration of clomipramine, one of the major tricyclic antidepressants used in humans. Two independent sets of experiment were performed in this study, in order to evaluate the effects of two different formulations based on the utilisation of the probiotic L. rhamnosus GG in its live or inactivated form. CUMS led to an impairment of the emotional state of 6-month-old mice. However, chronic treatment with a combination of glutamine, curcumin and L. rhamnosus GG rescued the anxiety and depressive-like phenotype with an efficiency similar to clomipramine. A synergistic effect of the three compounds was observed, suggesting that simultaneous action on different targets is a relevant approach for the management of anxiety-depressive disorders.

Published
2022
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9. Methylomic biomarkers of lithium response in bipolar disorder: a clinical utility study

Author

C. Marie-Claire, C. Courtin, F. Bellivier, S. Gard, M. Leboyer, J. Scott, and B. Etain

Subjects
Psychiatry and Mental health, Biological Psychiatry
Abstract

Background Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays able to discriminate good responders (GR) from non-responders (NR) to Li in individuals with BD type 1 (BD-I). This study examined whether a combination of clinical and epigenetic markers can distinguish NR from other types of Li responders. Methods We recorded clinical variables that are potentially associated with Li response in 64 individuals with BD-I. MS-HRM assays were performed on DNA isolated from peripheral blood. We used backward stepwise logistic regression analyses, followed by receiver operating characteristic (ROC) curve analysis to estimate the performance of the clinical variables, alone then in combination with the epigenetic biomarkers, to identify GR and partial responders (PaR) vs NR. Results Polarity at onset, psychotic symptoms at onset and family history of BD classified correctly 70% of individuals according to their Li response (PaR + GR = 86%; NR = 35%). When combined with the epigenetic biomarkers, these three clinical variables plus alcohol misuse (and one DMR: Differentially Methylated Region) correctly classified 86% of individuals, improving the prediction of PaR + GR (93%) and of NR (70%). The ROC analysis demonstrated an improvement in the area under the curve from 0.75 (clinical variables alone) to 0.87 (combination of clinical and epigenetic markers). Conclusions Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone.

Published
2023
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10. Clinical and pharmacological correlates of caffeine consumption in subjects with schizophrenia – Data from the FACE-SZ cohort

Author

Andrei Szoke, Jean-Romain Richard, Guillaume Fond, David Misdrahi, Mohamed Lajnef, Bruno Aouizerate, Laurent Boyer, Fabrice Berna, Delphine Capdevielle, Myrtille André, Isabelle Chereau, Julie Clauss-Kobayashi, Nathalie Coulon, Caroline Dubertret, Sylvain Leignier, Pierre Michel Llorca, Jasmina Mallet, Christine Passerieux, Romain Rey, Benoit Schorr, Mathieu Urbach, Marion Leboyer, Baptiste Pignon, Franck Schürhoff, M. Andre, C. Andrieu-Haller, B. Aouizerate, F. Berna, O. Blanc, E. Bourguignon, D. Capdevielle, I. Chereau-Boudet, J. Clauss-Kobayashi, N. Coulon, R. Dassing, J.M. Dorey, C. Dubertret, A. Esselin, G. Fond, F. Gabayet, M. Jarroir, D. Lacelle, M. Leboyer, S. Leignier, P.M. Llorca, J. Mallet, E. Metairie, T. Michel, D. Misdrahi, C. Passerieux, J. Petrucci, B. Pignon, P. Peri, C. Portalier, R. Rey, C. Roman, B. Schorr, F. Schürhoff, A. Szoke, A. Tessier, M. Urbach, G. Wachiche, A. Zinetti-Bertschy, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Grenoble, Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Psychiatry and Mental health, Caffeine, Sedation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Negative dimension, Biological Psychiatry
Abstract

International audience; Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = −0.12) but significant.

Published
2023
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11. Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study

Author

B. Pignon, H. Peyre, A. Ayrolles, J. B. Kirkbride, S. Jamain, A. Ferchiou, J. R. Richard, G. Baudin, S. Tosato, H. Jongsma, L. de Haan, I. Tarricone, M. Bernardo, E. Velthorst, M. Braca, C. Arango, M. Arrojo, J. Bobes, C. M. Del-Ben, M. Di Forti, C. Gayer-Anderson, P. B. Jones, C. La Cascia, A. Lasalvia, P. R. Menezes, D. Quattrone, J. Sanjuán, J. P. Selten, A. Tortelli, P. M. Llorca, J. van Os, B. P. F. Rutten, R. M. Murray, C. Morgan, M. Leboyer, A. Szöke, F. Schürhoff, Pignon B., Peyre H., Ayrolles A., Kirkbride J.B., Jamain S., Ferchiou A., Richard J.R., Baudin G., Tosato S., Jongsma H., de Haan L., Tarricone I., Bernardo M., Velthorst E., Braca M., Arango C., Arrojo M., Bobes J., Del-Ben C.M., Di Forti M., Gayer-Anderson C., Jones P.B., La Cascia C., Lasalvia A., Menezes P.R., Quattrone D., Sanjuan J., Selten J.P., Tortelli A., Llorca P.M., van Os J., Rutten B.P.F., Murray R.M., Morgan C., Leboyer M., Szoke A., Schurhoff F., Pignon, B [0000-0003-0526-3136], Ayrolles, A [0000-0002-3202-0781], Kirkbride, JB [0000-0003-3401-0824], Tosato, S [0000-0002-9665-7538], Lasalvia, A [0000-0001-9963-6081], Morgan, C [0000-0002-1386-2369], Apollo - University of Cambridge Repository, Pignon, B, Peyre, H, Ayrolles, A, Kirkbride, J B, Jamain, S, Ferchiou, A, Richard, J R, Baudin, G, Tosato, S, Jongsma, H, de Haan, L, Tarricone, I, Bernardo, M, Velthorst, E, Braca, M, Arango, C, Arrojo, M, Bobes, J, Del-Ben, C M, Di Forti, M, Gayer-Anderson, C, Jones, P B, La Cascia, C, Lasalvia, A, Menezes, P R, Quattrone, D, Sanjuán, J, Selten, J P, Tortelli, A, Llorca, P M, van Os, J, Rutten, B P F, Murray, R M, Morgan, C, Leboyer, M, Szöke, A, Schürhoff, F, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: VPK Flexteam IC (9), MUMC+: MA Psychiatrie (3), and RS: MHeNs - R3 - Neuroscience

Subjects
Schizophrenia/genetics, Environmental effects on human beings, Risk factors in diseases, Epidemiology, Psicosi, psychosi, Pathological psychology, Genes × environment interaction, Risk Factors, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, psychosocial stressors, Humans, psychosis, Psychotic Disorders/genetics, Settore MED/25 - Psichiatria, Influència del medi ambient en l'home, Genètica de la conducta, Factors de risc en les malalties, Genes × environment interactions, Public Health, Environmental and Occupational Health, Psychoses, polygenic risk score for schizophrenia, Psicopatologia, Psychiatry and Mental health, Psychotic Disorders, Behavior genetics, Schizophrenia, Esquizofrènia, Gene-Environment Interaction
Abstract

the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI) and FP7-HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS) (...), Pignon B, Peyre H, Ayrolles A, Kirkbride JB, Jamain S, Ferchiou A, Richard JR, Baudin G, Tosato S, Jongsma H, de Haan L, Tarricone I, Bernardo M, Velthorst E, Braca M, Arango C, Arrojo M, Bobes J, Del-Ben CM, Di Forti M, Gayer-Anderson C, Jones PB, La Cascia C, Lasalvia A, Menezes PR, Quattrone D, Sanjuán J, Selten JP, Tortelli A, Llorca PM, van Os J, Rutten BPF, Murray RM, Morgan C, Leboyer M, Szöke A, Schürhoff F

Published
2022
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13. Synergistic effects of

Author

P, Faucher, A, Dries, P Y, Mousset, M, Leboyer, J, Dore, and D, Beracochea

Subjects
Depressive Disorder, Disease Models, Animal, Mice, Curcumin, Depression, Lacticaseibacillus rhamnosus, Glutamine, Probiotics, Clomipramine, Animals, Humans, Infant, Stress, Psychological
Abstract

The microbiota-gut-brain axis is important in anxiety-depressive disorders. These conditions are associated with dysbiosis of the intestinal microbiota, intestinal hyperpermeability and an increase in circulating markers of inflammation and oxidative stress. They are also associated with a deregulation of the glutamine-glutamate-γ-aminobutyric acid cycle, with impairment of the excitatory/inhibitory balance in the brain. Our aim was to examine the impact of chronic treatment with the probiotic organism

Published
2022

15. A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort

Author

A. Schandrin, J. Norton, S. Raffard, B. Aouizerate, F. Berna, L. Brunel, I. Chereau-Boudet, T. D'Amato, H. Denizot, C. Dubertret, J. Dubreucq, C. Faget, G. Fond, F. Gabayet, P.M. Llorca, J. Mallet, D. Misdrahi, C. Passerieux, R. Rey, F. Schurhoff, M. Urbach, S. Bonnet, D. Capdevielle, M. Andrianarisoa, N. Bazin, O. Blanc, E. Bulzacka, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, L. Ramet, L. Rey, C. Roman, F. Schürhoff, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Université Montpellier 1 (UM1), Fondation FondaMental [Créteil], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Psychopathologie et pharmacologie de la cognition, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier le Vinatier [Bron], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Colombière, Centre hospitalier Charles Perrens [Bordeaux], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Strasbourg, Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], CHU Clermont-Ferrand, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Montpellier (UM), FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group: M Andrianarisoa 16 , B Aouizerate 17 , N Bazin 18 , F Berna 19 , O Blanc 20 , L Brunel 16 , E Bulzacka 16 , D Capdevielle 21 , I Chereau-Boudet 20 , G Chesnoy-Servanin 22 , J M Danion 19 , T D'Amato 22 , A Deloge 23 , C Delorme 24 , H Denizot 20 , J M Dorey 22 , C Dubertret 25 , J Dubreucq 24 , C Faget 26 , C Fluttaz 24 , G Fond 27 , S Fonteneau 18 , F Gabayet 24 , E Giraud-Baro 24 , D Lacelle 20 , C Lançon 26 , H Laouamri 27 , M Leboyer 16 , T Le Gloahec 16 , Y Le Strat 25 , P M Llorca 20 , J Mallet 25 , E Metairie 26 , D Misdrahi 23 , I Offerlin-Meyer 19 , C Passerieux 18 , P Peri 26 , S Pires 20 , C Portalier 25 , L Ramet 18 , L Rey 22 , C Roman 24 , A Schandrin 28 , F Schürhoff 16 , A Tessier 23 , A M Tronche 20 , M Urbach 18 , F Vaillant 26 , A Vehier 22 , P Vidailhet 19 , E Vilà 23 , H Yazbek 21 , A Zinetti-Bertschy 19, Hôpital Charles Perrens, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), and Centre de Psychiatrie et Neurosciences (U894)

Subjects
Adult, Male, Adolescent, media_common.quotation_subject, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Hostility, Anger, Cohort Studies, Diagnostic Self Evaluation, Young Adult, 03 medical and health sciences, Aggressiveness, 0302 clinical medicine, medicine, Humans, Spectrum disorder, ComputingMilieux_MISCELLANEOUS, Biological Psychiatry, media_common, Aggression, Middle Aged, Awareness, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Schizophrenia, Multi dimensional, Female, medicine.symptom, Insight, Psychology, 030217 neurology & neurosurgery, Diagnosis of schizophrenia, Clinical psychology
Abstract

International audience; Background: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.

Published
2019
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16. La conciliation médicamenteuse est-elle réalisable et pertinente en Psychiatrie ? : Retour d’expérience sur la mise en place de la conciliation à l’admission

Author

Muriel Paul, A. Leherle, A. Pelissolo, Z. Toulemon, M. Leboyer, M. Dalle-pecal, Catherine Divine, and C. Kowal

Subjects
Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Pharmaceutical Science, 030226 pharmacology & pharmacy, 030227 psychiatry
Abstract

Resume Objectif Le parcours de soins du patient souffrant de troubles psychiques etant un parcours complexe et a risque d’interruption de traitement, nous avons mis en place la conciliation medicamenteuse a l’admission en psychiatrie en fevrier 2017. L’objectif de ce travail a ete de realiser un retour d’experience repondant a nos questionnements sur la faisabilite et la pertinence de cette demarche. Methode Une analyse prospective des conciliations sur les 7 premiers mois de mise en place a ete realisee selon 3 indicateurs d’activite et 6 indicateurs de performance. Resultats Au total, 39 patients ont ete concilies dont 56,4 % en secteur ferme. La totalite des patients ont ete rencontres lors d’un entretien pharmaceutique. Les informations issues de cet entretien etaient concordantes avec au moins l’une des autres sources dans 70,4 % des cas. 13 patients n’ont pu etre concilies dans les 72 h en raison de leur pathologie psychiatrique. Le nombre moyen de divergences non intentionnelles (DNI) par conciliation etait de 0,97. Le taux de DNI de gravite majeure etait de 23,7 %. Le nombre de DNI par patient etait significativement superieur en secteur ferme (p Conclusion Ces resultats montrent que la conciliation d’entree est realisable et pertinente en psychiatrie. Pour limiter les contraintes liees a la pathologie psychiatrique, nous proposons de concilier les patients au-dela de 72h apres leur admission, des que leur etat clinique le permet.

Published
2020
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17. The relationship between immune and cognitive dysfunction in mood and psychotic disorder : a systematic review and a meta-analysis

Author

M. Morrens, C. Overloop, V. Coppens, E. Loots, M. Van Den Noortgate, S. Vandenameele, M. Leboyer, L. De Picker, Clinical and Lifespan Psychology, Faculty of Medicine and Pharmacy, Faculty of Sciences and Bioengineering Sciences, Clinical sciences, Psychiatry, and Neuroprotection & Neuromodulation

Subjects
bipolar disorder, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Chemistry, cognitive dysfunction, Psychotic Disorders/complications, Humans, biomarkers, Human medicine, Depressive Disorder, Major/complications, Molecular Biology, Biology
Abstract

Background In psychotic and mood disorders, immune alterations are hypothesized to underlie cognitive symptoms, as they have been associated with elevated blood levels of inflammatory cytokines, kynurenine metabolites, and markers of microglial activation. The current meta-analysis synthesizes all available clinical evidence on the associations between immunomarkers (IMs) and cognition in these psychiatric illnesses. Methods Pubmed, Web of Science, and Psycinfo were searched for peer-reviewed studies on schizophrenia spectrum disorder (SZ), bipolar disorder (BD), or major depressive disorder (MDD) including an association analysis between at least one baseline neuropsychological outcome measure (NP) and one IM (PROSPERO ID:CRD42021278371). Quality assessment was performed using BIOCROSS. Correlation meta-analyses, and random effect models, were conducted in Comprehensive Meta-Analysis version 3 investigating the association between eight cognitive domains and pro-inflammatory and anti-inflammatory indices (PII and AII) as well as individual IM. Results Seventy-five studies (n = 29,104) revealed global cognitive performance (GCP) to be very weakly associated to PII (r = −0.076; p = 0.003; I2 = 77.4) or AII (r = 0.067; p = 0.334; I2 = 38.0) in the combined patient sample. Very weak associations between blood–based immune markers and global or domain-specific GCP were found, either combined or stratified by diagnostic subgroup (GCP x PII: SZ: r = −0.036, p = 0.370, I2 = 70.4; BD: r = −0.095, p = 0.013, I2 = 44.0; MDD: r = −0.133, p = 0.040, I2 = 83.5). We found evidence of publication bias. Discussion There is evidence of only a weak association between blood-based immune markers and cognition in mood and psychotic disorders. Significant publication and reporting biases were observed and most likely underlie the inflation of such associations in individual studies.

Published
2022

19. Psychiatric and physical outcomes of long-term use of lithium in older adults with bipolar disorder and major depressive disorder: A cross-sectional multicenter study

Author

Elise Morlet, Jean-François Costemale-Lacoste, Emmanuel Poulet, Kibby McMahon, Nicolas Hoertel, Frédéric Limosin, J Adès, C Alezrah, I Amado, G Amar, O Andréi, D Arbault, G Archambault, G Aurifeuille, S Barrière, C Béra-Potelle, Y Blumenstock, H Bardou, M Bareil-Guérin, P Barrau, C Barrouillet, E Baup, N Bazin, B Beaufils, J Ben Ayed, M Benoit, K Benyacoub, T Bichet, F Blanadet, O Blanc, J Blanc-Comiti, D Boussiron, AM Bouysse, A Brochard, O Brochart, B Bucheron, M Cabot, V Camus, JM Chabannes, V Charlot, T Charpeaud, C Clad-Mor, C Combes, M Comisu, B Cordier, F Costi, JP Courcelles, M Creixell, H Cuche, C Cuervo-Lombard, A Dammak, D Da Rin, JB Denis, H Denizot, A Deperthuis, E Diers, S Dirami, D Donneau, P Dreano, C Dubertret, E Duprat, D Duthoit, C Fernandez, P Fonfrede, N Freitas, P Gasnier, J Gauillard, F Getten, F Gierski, F Godart, R Gourevitch, A Grassin Delyle, J Gremion, H Gres, V Griner, C Guerin-Langlois, C Guggiari, O Guillin, H Hadaoui, E Haffen, C Hanon, S Haouzir, C Hazif-Thomas, A Heron, B Hubsch, I Jalenques, D Januel, A Kaladjian, JF Karnycheff, O Kebir, MO Krebs, C Lajugie, M Leboyer, P Legrand, M Lejoyeux, V Lemaire, E Leroy, D Levy-Chavagnat, A Leydier, C Liling, PM Llorca, P Loeffel, P Louville, S Lucas Navarro, N Mages, M Mahi, O Maillet, A Manetti, C Martelli, P Martin, M Masson, I Maurs-Ferrer, J Mauvieux, S Mazmanian, E Mechin, L Mekaoui, M Meniai, A Metton, A Mihoubi, M Miron, G Mora, V Niro Adès, P Nubukpo, C Omnes, S Papin, P Paris, C Passerieux, J Pellerin, J Perlbarg, S Perron, A Petit, F Petitjean, C Portefaix, D Pringuey, A Radtchenko, H Rahiou, D Raucher-Chéné, A Rauzy, L Reinheimer, M Renard, M René, CE Rengade, P Reynaud, D Robin, C Rodrigues, A Rollet, F Rondepierre, B Rousselot, S Rubingher, G Saba, JP Salvarelli, JC Samuelian, C Scemama-Ammar, F Schurhoff, JP Schuster, D Sechter, B Segalas, T Seguret, AS Seigneurie, A Semmak, F Slama, S Taisne, M Taleb, JL Terra, D Thefenne, E Tran, R Tourtauchaux, MN Vacheron, P Vandel, V Vanhoucke, E Venet, H Verdoux, A Viala, G Vidon, M Vitre, JL Vurpas, C Wagermez, M Walter, L Yon, X. Zendjidjian, Service de psychiatrie [Le Kremlin-Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier le Vinatier [Bron], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), PELLENC S.A., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Society for Biological Psychiatry and Neuropsychopharmacology, Partenaires INRAE, Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Département d'Astrophysique (ex SAP) (DAP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli studi di Genova = University of Genoa (UniGe), Fondation FondaMental [Créteil], Fédération Française de Triathlon (FFTRI), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cognition, Santé, Société (C2S), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service hospitalo-universitaire, centre hospitalier du Rouvray, 4, rue Paul-Eluard, 76300 Sotteville-lès-Rouen, France., CHRU Brest - Psychiatrie Adulte (CHU - Brest- Psychiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Physique Théorique [Palaiseau] (CPHT), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centres d'addictologies - Région Centre, CHU Clermont-Ferrand, Unité de recherche clinique 93G03, établissement public de santé de Ville Evrard, 93330 Neuilly-sur-Marne, France., Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Sonatrach Exploration, Monash University [Clayton], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Clinique de Psychiatrie et de Psychologie Médicale, Hôpital Pasteur, Nice, France, Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Engineering Cybernetics [Trondheim] (ITK NTNU), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Jeune Equipe Hémopathogènes Vectorisés, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Silicon-on-Insulator Technologies (SOITEC), Parc Technologique des Fontaines, Recherches en Psychopathologie, nouveaux symptômes et lien social (EA 4050), Université de Poitiers-Université de Brest (UBO)-Université Catholique de l'Ouest (UCO)-Université de Rennes 2 (UR2), Agriculture et forêt méditerranéenne (UR AFAX), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Kantar – Health Division, Institut National de Recherche en Génie Rural Eaux et Forêts (INRGREF), Ecole Nationale du Génie Rural, des Eaux et des Forêts (ENGREF)-Institution de la Recherche et de l'Enseignement Supérieur Agricoles [Tunis] (IRESA), Département de psychiatrie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Pôle Universitaire de Psychiatrie Adulte, Différenciation et communication neuronale et neuroendocrine (DC2N), Centre de Psychiatrie et Neurosciences (U894), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Dipartimento di Scienze della Terra, Universita degli studi di Genova, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
Male, Aging, medicine.medical_specialty, Bipolar Disorder, Lithium (medication), Population, [SHS.PSY]Humanities and Social Sciences/Psychology, Comorbidity, [SHS]Humanities and Social Sciences, law.invention, Benzodiazepines, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, Bipolar disorder, education, Psychiatry, ComputingMilieux_MISCELLANEOUS, Aged, Depressive Disorder, Major, education.field_of_study, Depression, business.industry, Middle Aged, medicine.disease, Antidepressive Agents, 3. Good health, 030227 psychiatry, Hospitalization, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Mood disorders, Tolerability, Schizophrenia, Lithium Compounds, Major depressive disorder, Female, business, 030217 neurology & neurosurgery, Antipsychotic Agents, medicine.drug
Abstract

Although lithium is widely used in current practice to treat bipolar disorder (BD) and treatment-resistant major depressive disorder (MDD) among older adults, little is known about its efficacy and tolerability in this population, which is generally excluded from randomized clinical trials. The objective of this study was to evaluate the efficacy and tolerability of long-term use of lithium among older adults with BD and MDD.Data from the Cohort of individuals with Schizophrenia and mood disorders Aged 55 years or more (CSA) were used. Two groups of patients with BD and MDD were compared: those who were currently receiving lithium versus those who were not. The effects of lithium on psychiatric (i.e., depressive symptoms severity, perceived clinical severity, rates of psychiatric admissions in the past-year), geriatric (overall and cognitive functioning) and physical outcomes (i.e., rates of non-psychiatric medical comorbidities and general hospital admissions in the past-year) were evaluated. All analyses were adjusted for age, sex, duration of disorder, diagnosis, smoking status, alcohol use, and use of antipsychotics, antiepileptics or antidepressants.Among the 281 older participants with BD or MDD, 15.7% were taking lithium for a mean duration of 12.5(SD = 11.6) years. Lithium use was associated with lower intensity of depressive symptoms, reduced perceived clinical global severity and lower benzodiazepine use (all p 0.05), without being linked to greater rates of medical comorbidities, except for hypothyroidism.Data were cross-sectional and data on lifetime history of psychotropic medications was not assessed.Our results suggest that long-term lithium use may be efficient and relatively well-tolerated in older adults with BD or treatment-resistant MDD.

Published
2019
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21. Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort

Author

M. Leboyer, O. Godin, P.M. Llorca, V. Aubin, F. Bellivier, R. Belzeaux, P. Courtet, D. Costagliola, C. Dubertret, K. M'Bailara, E. Haffen, C. Henry, H. Laouamri, C. Passerieux, A. Pelletier, M. Polosan, P. Roux, R. Schwan, L. Samalin, E. Olié, Bruno Etain, B. Etain, V. Barteau, S. Bensalem, K. Souryis, S. Hotier, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Wuillaume, E. Bourdin, M. Carminati, V. Hennion, E. Marlinge, J. Meheust, C. Zekri, A. Desage, S. Gard, I. Minois, J. Sportich, L. Zanouy, C. Abettan, L. Bardin, A. Cazals, B. Deffinis, D. Ducasse, M. Gachet, A. Henrion, E. Martinerie, F. Molière, B. Noisette, E.G. Tarquini, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Fondation FondaMental [Créteil], CHU Clermont-Ferrand, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre Hospitalier Princesse Grace, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], Laboratoire de psychologie:Santé et qualité de vie, Université Bordeaux Segalen - Bordeaux 2, Hôpital Charles Perrens, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université de Lorraine (UL), This research was supported by the Foundation FondaMental, Institut National de la Sant ́e et de la Recherche M ́edicale (INSERM), AP-HP, and by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. Thisfunding source had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript forpublication., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire Épidémiologie et biostatistique, Santé publique, Pharmacie, Pharmacologie, Recherche, Information médicale, Thérapeutique et médicaments) (DMU Esprit), Laboratoires de neurosciences intégratives et cliniques (EA 481), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), IMRB - 'Biologie du système neuromusculaire' [Créteil] (U955 Inserm - UPEC), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, FondaMental Advanced Center of Expertise for Bipolar Disorders (FACE-BD) collaborators : B.Etain, E.Olié, M.Leboyer, P.M.Llorca, V.Barteau, S.Bensalem, O.Godin, H.Laouamri, K.Souryis, S.Hotier, A.Pelletier, J.P.Sanchez, E.Saliou, C.Hebbache, J.Petrucci, L.Wuillaume, E.Bourdin, F.Bellivier, M.Carminati, V.Hennion, E.Marlinge, J.Meheust, C.Zekri, A.Desage, S.Gard, K.M'Bailara, I.Minois, J.Sportich, L.Zanouy, C.Abettan, L.Bardin, A.Cazals, P.Courtet, B.Deffinis, D.Ducasse, M.Gachet, A.Henrion, E.Martinerie, F.Molière, B.Noisette, E.G.Tarquini., CHU Henri Mondor [Créteil], Centre hospitalier Charles Perrens [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Godin, Ophélia

Subjects
Bipolar Disorder, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Suicide, Attempted, Comorbidity, Environment, Anxiety Disorders, Longitudinal, Cohort Studies, Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Bipolar disorders, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Course, ComputingMilieux_MISCELLANEOUS, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort.Method & results: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning.Conclusions: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.

Published
2021
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22. [Use of antidepressants in unipolar depression in the elderly]

Author

A, Pericaud, C, Straczek, F, Montastruc, M, Leboyer, A, Yrondi, and C, Arbus

Subjects
Depressive Disorder, Major, Treatment Outcome, Humans, Antidepressive Agents, Aged, Systematic Reviews as Topic
Abstract

To study the ageing-related pharmacological modifications about major depressive episodes in the elderly and their impact on the efficiency and tolerability of antidepressants.Research through Pubmed and the Cochrane Database of Systematic Reviews, using the following keywords "antidepressant" ; "treatment"; "late life depression"; "elderly"; up until July 2021.Antidepressants were found to be more efficient than a placebo in the elderly's response to and remission from major depressive episodes. Some depressive episode subtypes seem to be less responsive to antidepressants, such as depressive episodes of vascular origin, for which treating cardiovascular risk factors by statins, angiotensin receptor blockers or calcium channel blockers seems relevant. Two other depressive episode subtypes were highlighted : post-stroke depressive episodes and those induced by major neurocognitive disorders. Antidepressants showed an efficient response in the first case but not in the second. Even though antidepressants are known to stimulate cognitive performances in animals, as yet there is not sufficient evidence to prove they indeed improve cognitive functions, or reduce the risk of developing a neurocognitive disorder, or decelerate the cognitive decline in major neurocognitive disorders in humans. Ageing creates pharmacodynamical changes that increase older people's vulnerability to the side effects of antidepressants. Moreover, age-related pharmacokinetic modifications can also change every step in a drug's transformation process in the body, which leads to a high probability of having adverse effects. Since most antidepressants are eliminated using the P450 cytochrome system, their dosage must be adapted to changes of the P450 system. Somatic comorbidities can, in themselves, influence the pharmacokinetics of antidepressants. Many antidepressants interact with the P450 cytochrome and the P-GP protein, which puts them at a high risk of drug interactions. There is no proven efficiency difference between antidepressant classes. Some antidepressant adverse effects can be of particular importance in the elderly, like the risk of bleeding, cardiovascular episodes, hyponatremia, falling and fractures, anticholinergic effects, extrapyramidal syndrome, epilepsy, liver disease and death. Selective serotonin reuptake inhibitors have an indication as the first line of treatment, avoiding paroxetine and fluoxetine. Serotonin and norepinephrine re-uptake inhibitors are relevant if the patient presents psychomotor retardation or pain, while keeping in mind to check blood pressure. Tricyclics and monoamine oxidase inhibitors should be avoided because of their anticholinergic effects. Bupropion can be prescribed if the patient has extreme fatigue. Mirtazapine is useful when the patient presents sleep or appetite disturbance. Several molecules can be used in the case of drug-resistant depression, such as associating aripiprazole with small-dosage antidepressants, or electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation (rTMS). Ketamine and psychostimulants seem to have antidepressant effects, but complementary studies are needed to conclude.Unipolar major depressive episodes in the elderly are frequent and their medicinal treatment has specific features. Knowing the specificities of antidepressant use in the elderly allows to optimize its efficiency and to limit the risk of inappropriate prescription leading to harmful adverse effects.

Published
2021

23. Which actigraphic variables optimally characterize the sleep-wake cycle of individuals with bipolar disorders?

Author

Sunthavy Yeim, Jan Scott, C Nevoret, Bruno Etain, M. Leboyer, Chloé Benizri, Karoline Krane-Gartiser, J. Maruani, H Brochard, V Benard, Sandrine Katsahian, Franck Bellivier, and Pierre A. Geoffroy

Subjects
Adult, Male, Sleep Wake Disorders, medicine.medical_specialty, Bipolar Disorder, Audiology, 03 medical and health sciences, 0302 clinical medicine, Discriminant function analysis, Humans, Medicine, Circadian rhythm, Bipolar disorder, Depressive symptoms, business.industry, Area under the curve, Actigraphy, Middle Aged, medicine.disease, Sleep in non-human animals, 030227 psychiatry, Psychiatry and Mental health, Increased risk, Case-Control Studies, Female, business, 030217 neurology & neurosurgery
Abstract

Objective To examine which combination of objectively measured actigraphy parameters best characterizes the sleep-wake cycle of euthymic individuals with bipolar disorder (BD) compared with healthy controls (HC). Methods Sixty-one BD cases and 61 matched HC undertook 21 consecutive days of actigraphy. Groups were compared using discriminant function analyses (DFA) that explored dimensions derived from mean values of sleep parameters (Model 1); variability of sleep parameters (2); daytime activity (3); and combined sleep and activity parameters (4). Exploratory within-group analyses examined characteristics associated with misclassification. Results After controlling for depressive symptoms, the combined model (4) correctly classified 75% cases, while the sleep models (1 and 2) correctly classified 87% controls. The area under the curve favored the combined model (0.86). Age was significantly associated with misclassification among HC, while a diagnosis of BD-II was associated with an increased risk of misclassifications of cases. Conclusion Including sleep variability and activity parameters alongside measures of sleep quantity improves the characterization of cases of euthymic BD and helps distinguish them from HC. If replicated, the findings indicate that traditional approaches to actigraphy (examining mean values for the standard set of sleep parameters) may represent a suboptimal approach to understanding sleep-wake cycles in BD.

Published
2019
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24. Clinical characteristics of obstructive sleep apnea in bipolar disorders

Author

Jean-Arthur Micoulaud Franchi, Bruno Etain, C. Boudebesse, Pierre-Alexis Geoffroy, Pierre Philip, Frank Bellivier, Julia Maruani, H Brochard, M. Leboyer, Victoire Benard, Chloé Benizri, and Sunthavy Yeim

Subjects
Adult, Male, medicine.medical_specialty, Bipolar Disorder, Polysomnography, Comorbidity, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Trial number, stomatognathic system, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires, Internal medicine, medicine, Humans, Bipolar disorder, Depression (differential diagnoses), Aged, Sleep Apnea, Obstructive, medicine.diagnostic_test, Depression, business.industry, Actigraphy, Middle Aged, medicine.disease, Obesity, nervous system diseases, respiratory tract diseases, 030227 psychiatry, Obstructive sleep apnea, Psychiatry and Mental health, Clinical Psychology, ROC Curve, Subjective sleep, Female, business, 030217 neurology & neurosurgery
Abstract

Obstructive sleep apnea (OSA) is one of the leading non-psychiatric comorbidities in bipolar disorders (BD). We sought to explore associations between risk of OSA in BD, clinical characteristics alongside with both subjective sleep complaints and objective sleep abnormalities.Euthymic patients with BD (n = 144) were assessed over a three-week period, by actigraphy, clinical interviews and questionnaires.Of the study sample, 32 (22%) individuals were at high risk of OSA (HR-OSA) and 112 (78%) had a low risk (LR-OSA), as assessed with the Berlin questionnaire. HR-OSA, compared to LR-OSA, were older (p = 0.031), had higher BMI (p 0.0005), larger neck circumference (p = 0.002), and more residual depressive symptoms (p 0.0005). HR-OSA was also associated with greater sleepiness (p = 0.003), poorer sleep quality (p = 0.003), insomnia complaints (p = 0.027), "languid" chronotype (p = 0.002), and higher actigraphy-derived fragmentation index (p = 0.015). Backward stepwise linear regression retained BMI and depressive symptoms (correct classification of 83% of participants). Classification increased up to 85.4% when adding sleepiness and languid-vigorous scales and up to 87.8% when adding fragmentation index. Combining ROC curve analysis and Youden Index provided best cut-offs (HR-OSA if cut-off greater than or equal to) of 29.84 for BMI (Sensibility(Se) = 0.47, Specificity(Spe) = 0.96) and 1.5 for MADRS total score (Se = 0.84, Spe = 0.58).No confirmation of OSA diagnosis with polysomnography.Higher BMI and residual depressive symptoms are the two best independent predictors of OSA in BD. Such information contributes to improving the screening and management of OSA in BD.NCT02627404.

Published
2019
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25. Clinical predictors of kynurenine pathway aberrations in schizophrenia and bipolar disorder

Author

K. Skorobogatov, M. Leboyer, M. Foiselle, M. Morrens, and L. De Picker

Subjects
Psychiatry and Mental health
Abstract

Introduction Schizophrenia and bipolar disorder are severe mental illnesses that are known to have a considerable overlap in underlying pathophysiological mechanisms. More specifically, disturbances in the kynurenine pathway have been hypothesized as processes bridging altered immune responses and clinical manifestations of these illnesses. Objectives The aim of this study was to investigate the abnormalities in serum kynurenine metabolites in schizophrenic and bipolar patients and the impact of clinical factors. Methods Four patient groups were included in the current study: 1) Acute bipolar inpatients (n=205); 2) stable bipolar outpatients (n=116); 3) acute schizophrenia inpatients (n=111) and 4) stable schizophrenia outpatients (n=75); and one healthy control group (n=185). Clinical symptoms were established using symptom severity scales. The quantitative determination of serum kynurenine metabolites was performed using LC-MS/MS. General linear model and multivariate linear regression analyses were used to perform the statistical analysis with JMP Pro 15. Results In line with previous research, the results indicate that serum kynurenine metabolites are disturbed in schizophrenic and bipolar patients compared to healthy controls. Whereas no differences were observed between schizophrenia and bipolar disorder, illness state and duration of illness clearly impacted kynurenine metabolite levels. Acutely ill patients had significantly lower levels compared to stable patients, which seemed to be driven by psychotic symptoms. Conclusions To conclude, the results confirm the involvement of the kynurenine pathway in the pathophysiology of schizophrenia and bipolar disorder by lowered peripheral kynurenine metabolite level. In addition, an important role of acute psychotic symptoms and longer illness duration on these metabolite aberrances is demonstrated. Disclosure No significant relationships.

Published
2022
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26. A multicentric multimodal in vivo microscopy MRI study of bipolar disorder reveals axonal loss and demyelination

Author

S. Sarrazin, C. Poupon, I. Uszynski, J.-F. Mangin, M. Polosan, P. Favre, C. Laidi, M.-A. D’Albis, M. Leboyer, P.-M. Lledo, C. Henry, L. Emsell, M. Shakeel, V. Goghari, and J. Houenou

Subjects
Psychiatry and Mental health
Abstract

Introduction Bipolar disorder has been repeatedly associated with abnormalities of white matter. However, DTI is intrinsically limited and the precise cellular mechanisms that underlie these alterations remains unknown. Objectives Our aim was to investigate microscopical characteristics of white matter using MRI in patients with bipolar and healthy controls. Methods 77 patients and 71 controls from 3 sites had a T1 structural MRI, a multi-shell HARDI MRI and at one site with a T1-weighted VFA-SPGR acquisition, and a T2 MSME acquisition. The volume fraction and the orientation dispersion was extracted using NODDI from DW images in each site. Myelin Water Fraction was extracted in 33 patients and 36 controls to probe myelin characteristics. White matter bundles were reconstructed using deterministic tractography. Statistical analyses were performed after harmonization by the ComBat algorithm and controlled for age, gender and handedness. Results We found significant lower axonal density in patients along the short fibers of the left cingulum, the left anterior arcuate and the left inferior fronto-occipital fasciculus. We found lower mean MWF in patients along the short fibers of the right cingulum, the left inferior fronto-occipital fasciculus, the left anterior arcuate and the splenium of the corpus callosum. We found higher mean orientation dispersion in patients only along the left uncinate fasciculus. Conclusions We report alterations of limbic and inter-hemispheric white matter tracts in patients with bipolar disorder reflecting axonal loss, demyelination and architecture alterations. These results contribute to better capture the plurality of the mechanisms involved in bipolar disorder that cannot be deciphered with classical diffusion MRI. Disclosure No significant relationships.

Published
2022
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27. A conceptual framework to develop a patient-reported experience measure of the quality of mental health care: a qualitative study of the PREMIUM project in France

Author

P.-M. Llorca, F. Schürhoff, Bruno Aouizerate, Guillaume Fond, Ludovic Samalin, M. Leboyer, David Misdrahi, Magali Coldefy, Sara Fernandes, C. Henry, Pierre Michel, Pascal Auquier, L. Boyer, Fabrice Berna, Bruno Etain, X. Zendjidjian, Christophe Lançon, and Karine Baumstarck

Subjects
HF5001-6182, media_common.quotation_subject, macromolecular substances, Nursing, quality of care, severe mental illness, Patient experience, Business, Quality (business), Original Research Article, media_common, bipolar disorder, Measure (data warehouse), major depressive disorder, patient experience, A domain, Health services research, health services research, psychiatry, schizophrenia, Conceptual framework, Mental health care, Public aspects of medicine, RA1-1270, Psychology, qualitative research, Qualitative research, Research Article, Patient-reported experience measures
Abstract

Background: The objective of this study was to develop a conceptual framework to define a domain map describing the experience of patients with severe mental illnesses (SMIs) on the quality of mental health care. Methods: This study used an exploratory qualitative approach to examine the subjective experience of adult patients (18–65 years old) with SMIs, including schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Participants were selected using a purposeful sampling method. Semistructured interviews were conducted with 37 psychiatric inpatients and outpatients recruited from the largest public hospital in southeastern France. Transcripts were subjected to an inductive analysis by using two complementary approaches (thematic analysis and computerized text analysis) to identify themes and subthemes. Results: Our analysis generated a conceptual model composed of 7 main themes, ranked from most important to least important as follows: interpersonal relationships, care environment, drug therapy, access and care coordination, respect and dignity, information and psychological care. The interpersonal relationships theme was divided into 3 subthemes: patient-staff relationships, relations with other patients and involvement of family and friends. All themes were spontaneously raised by respondents. Conclusion: This work provides a conceptual framework that will inform the subsequent development of a patient-reported experience measure to monitor and improve the performance of the mental health care system in France. The findings showed that patients with SMIs place an emphasis on the interpersonal component, which is one of the important predictors of therapeutic alliance. Trial registration: NCT02491866

Published
2021

28. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Mullins, N. Forstner, A.J. O’Connell, K.S. Coombes, B. Coleman, J.R.I. Qiao, Z. Als, T.D. Bigdeli, T.B. Børte, S. Bryois, J. Charney, A.W. Drange, O.K. Gandal, M.J. Hagenaars, S.P. Ikeda, M. Kamitaki, N. Kim, M. Krebs, K. Panagiotaropoulou, G. Schilder, B.M. Sloofman, L.G. Steinberg, S. Trubetskoy, V. Winsvold, B.S. Won, H.-H. Abramova, L. Adorjan, K. Agerbo, E. Al Eissa, M. Albani, D. Alliey-Rodriguez, N. Anjorin, A. Antilla, V. Antoniou, A. Awasthi, S. Baek, J.H. Bækvad-Hansen, M. Bass, N. Bauer, M. Beins, E.C. Bergen, S.E. Birner, A. Bøcker Pedersen, C. Bøen, E. Boks, M.P. Bosch, R. Brum, M. Brumpton, B.M. Brunkhorst-Kanaan, N. Budde, M. Bybjerg-Grauholm, J. Byerley, W. Cairns, M. Casas, M. Cervantes, P. Clarke, T.-K. Cruceanu, C. Cuellar-Barboza, A. Cunningham, J. Curtis, D. Czerski, P.M. Dale, A.M. Dalkner, N. David, F.S. Degenhardt, F. Djurovic, S. Dobbyn, A.L. Douzenis, A. Elvsåshagen, T. Escott-Price, V. Ferrier, I.N. Fiorentino, A. Foroud, T.M. Forty, L. Frank, J. Frei, O. Freimer, N.B. Frisén, L. Gade, K. Garnham, J. Gelernter, J. Giørtz Pedersen, M. Gizer, I.R. Gordon, S.D. Gordon-Smith, K. Greenwood, T.A. Grove, J. Guzman-Parra, J. Ha, K. Haraldsson, M. Hautzinger, M. Heilbronner, U. Hellgren, D. Herms, S. Hoffmann, P. Holmans, P.A. Huckins, L. Jamain, S. Johnson, J.S. Kalman, J.L. Kamatani, Y. Kennedy, J.L. Kittel-Schneider, S. Knowles, J.A. Kogevinas, M. Koromina, M. Kranz, T.M. Kranzler, H.R. Kubo, M. Kupka, R. Kushner, S.A. Lavebratt, C. Lawrence, J. Leber, M. Lee, H.-J. Lee, P.H. Levy, S.E. Lewis, C. Liao, C. Lucae, S. Lundberg, M. MacIntyre, D.J. Magnusson, S.H. Maier, W. Maihofer, A. Malaspina, D. Maratou, E. Martinsson, L. Mattheisen, M. McCarroll, S.A. McGregor, N.W. McGuffin, P. McKay, J.D. Medeiros, H. Medland, S.E. Millischer, V. Montgomery, G.W. Moran, J.L. Morris, D.W. Mühleisen, T.W. O’Brien, N. O’Donovan, C. Olde Loohuis, L.M. Oruc, L. Papiol, S. Pardiñas, A.F. Perry, A. Pfennig, A. Porichi, E. Potash, J.B. Quested, D. Raj, T. Rapaport, M.H. DePaulo, J.R. Regeer, E.J. Rice, J.P. Rivas, F. Rivera, M. Roth, J. Roussos, P. Ruderfer, D.M. Sánchez-Mora, C. Schulte, E.C. Senner, F. Sharp, S. Shilling, P.D. Sigurdsson, E. Sirignano, L. Slaney, C. Smeland, O.B. Smith, D.J. Sobell, J.L. Søholm Hansen, C. Soler Artigas, M. Spijker, A.T. Stein, D.J. Strauss, J.S. Świątkowska, B. Terao, C. Thorgeirsson, T.E. Toma, C. Tooney, P. Tsermpini, E.-E. Vawter, M.P. Vedder, H. Walters, J.T.R. Witt, S.H. Xi, S. Xu, W. Yang, J.M.K. Young, A.H. Young, H. Zandi, P.P. Zhou, H. Zillich, L. Adolfsson, R. Agartz, I. Alda, M. Alfredsson, L. Babadjanova, G. Backlund, L. Baune, B.T. Bellivier, F. Bengesser, S. Berrettini, W.H. Blackwood, D.H.R. Boehnke, M. Børglum, A.D. Breen, G. Carr, V.J. Catts, S. Corvin, A. Craddock, N. Dannlowski, U. Dikeos, D. Esko, T. Etain, B. Ferentinos, P. Frye, M. Fullerton, J.M. Gawlik, M. Gershon, E.S. Goes, F.S. Green, M.J. Grigoroiu-Serbanescu, M. Hauser, J. Henskens, F. Hillert, J. Hong, K.S. Hougaard, D.M. Hultman, C.M. Hveem, K. Iwata, N. Jablensky, A.V. Jones, I. Jones, L.A. Kahn, R.S. Kelsoe, J.R. Kirov, G. Landén, M. Leboyer, M. Lewis, C.M. Li, Q.S. Lissowska, J. Lochner, C. Loughland, C. Martin, N.G. Mathews, C.A. Mayoral, F. McElroy, S.L. McIntosh, A.M. McMahon, F.J. Melle, I. Michie, P. Milani, L. Mitchell, P.B. Morken, G. Mors, O. Mortensen, P.B. Mowry, B. Müller-Myhsok, B. Myers, R.M. Neale, B.M. Nievergelt, C.M. Nordentoft, M. Nöthen, M.M. O’Donovan, M.C. Oedegaard, K.J. Olsson, T. Owen, M.J. Paciga, S.A. Pantelis, C. Pato, C. Pato, M.T. Patrinos, G.P. Perlis, R.H. Posthuma, D. Ramos-Quiroga, J.A. Reif, A. Reininghaus, E.Z. Ribasés, M. Rietschel, M. Ripke, S. Rouleau, G.A. Saito, T. Schall, U. Schalling, M. Schofield, P.R. Schulze, T.G. Scott, L.J. Scott, R.J. Serretti, A. Shannon Weickert, C. Smoller, J.W. Stefansson, H. Stefansson, K. Stordal, E. Streit, F. Sullivan, P.F. Turecki, G. Vaaler, A.E. Vieta, E. Vincent, J.B. Waldman, I.D. Weickert, T.W. Werge, T. Wray, N.R. Zwart, J.-A. Biernacka, J.M. Nurnberger, J.I. Cichon, S. Edenberg, H.J. Stahl, E.A. McQuillin, A. Di Florio, A. Ophoff, R.A. Andreassen, O.A. HUNT All-In Psychiatry

Abstract

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2021

29. Clinical predictors of recurrences in bipolar disorders type 1 and 2: A FACE-BD longitudinal study

Author

B. Etain, F. Bellivier, E. Olié, B. Aouizerate, V. Aubin, R. Belzeaux, P. Courtet, C. Dubertret, R. Schwan, P. Roux, M. Polosan, M. Leboyer, O. Godin, P.M. Llorca, C. Henry, V. Barteau, S. Bensalem, H. Laouamri, K. Souryis, S. Hotier, A. Pelletier, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Willaume, E. Bourdin, M. Carminati, J. Maruani, E. Marlinge, J. Meheust, B. Antoniol, A. Desage, S. Gard, A. Jutant, K. Mbailara, I. Minois, L. Zanouy, C. Abettan, L. Bardin, A. Cazals, B. Deffinis, D. Ducasse, M. Gachet, A. Henrion, E. Martinerie, F. Molière, B. Noisette, G. Tarquini, J.M. Azorin, N. Correard, J.L. Consoloni, F. Groppi, L. Lescalier, J. Montant, M. Rebattu, N. Viglianese, R. Cohen, G. Gross, T. Schwitzer, O. Wajsbrot-Elgrabli, T. Bougerol, B. Fredembach, A. Suisse, B. Halili, Z. Gaoua, A.S. Cannavo, A.M. Galliot, I. Grévin, N. Kayser, G. Liaskovski, C. Passerieux, I. Cussac, M.A. Dupont, J. Loftus, I. Medecin, N. Mazer, C. Portalier, C. Scognamiglio, A. Bing, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Fondation FondaMental [Créteil], Hôpital Fernand Widal, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Integrated Nutrition and Neurobiology, UMR 1286, INRA, Centre Hospitalier Princesse Grace, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Medico-surgical ICU, Assistance Publique - Hôpitaux de Paris, DMU ESPRIT, Médecine Intensive Réanimation, Hôpital Louis Mourier, 92700, Colombes, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Inserm, U1216, Grenoble, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Versailles André Mignot (CHV), ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Ministère des Affaires Sociales et de la Santé, This research was supported by the Foundation FondaMental , Institut National de la Santé et de la Recherche Médicale (INSERM) , AP-HP , and by the Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. This funding source had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., This research was supported by the Foundation FondaMental, Institut National de la Sant? et de la Recherche M?dicale (INSERM), AP-HP, and by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. This funding source had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., The study sample consisted in patients evaluated in the French network of FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD). This network is supported by the French Ministry of Health and has been developed under the aegis of the FondaMental Foundation, to provide support to general practitioners and psychiatrists in the diagnosis and management of patients with BD., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
medicine.medical_specialty, Longitudinal study, Clinical variables, Bipolar disorder, Subtype, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Daily practice, medicine, Humans, Longitudinal Studies, Age of Onset, First Recurrence, Biological Psychiatry, business.industry, medicine.disease, 030227 psychiatry, Affect, Psychiatry and Mental health, Mood, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Prediction, 030217 neurology & neurosurgery
Abstract

International audience; Objective: To examine which characteristics predict the time to a first mood recurrence at three years in Bipolar Disorder type I (BD-I) and type II (BD-II). Methods: Individuals with BD were followed up to 3 years. Turbull's extension of the Kaplan-Meier analysis for interval-censored data was used to estimate the cumulative probability of recurrence over time. Separate models were performed according to BD subtype to determine which baseline factors were predictive of recurrences and were adjusted for age, gender and educational level. Results: We included 630 individuals with BD-I and 505 with BD-II. The first recurrence of any polarity occurred earlier in BD-II (p = 0.03). The first depressive recurrence occurred earlier in BD-II (p < 0.0001), whereas the first (hypo)manic recurrence occurred earlier in BD-I (p = 0.0003). In BD-I, the clinical variables that were associated to the time to a first mood recurrence were depressive symptoms, lifetime rapid cycling, global activation and the number of psychotropic medications at baseline. In BD-II, the time to a first recurrence was associated with a younger age at onset of BD and a higher number of lifetime mood episodes. The Areas Under the Curve for both models were moderate. Conclusion: Predictors of recurrences showed few specificities to BD-I or BD-II. The ability to predict recurrences in BD based on socio-demographic and clinical variables remained too moderate for a transfer in daily practice. This study highlights the need for further studies that would include other types of predictors, such as molecular, cognitive or neuro-imaging ones, to achieve an accurate level of prediction of recurrences in BD.

Published
2021
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30. Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study

Author

Guillaume Fond, Philippe Le Corvoisier, F Schürhoff, A Szöke, Face-Sz Groups, I Offerlin-Meyer, Ryad Tamouza, T D′Amato, I Chéreau, J Dubreucq, E Vilà, F Gabayet, Julien Dubreucq, C Fluttaz, Wahid Boukouaci, D Misdrahi, P Vidailhet, David Misdrahi, J Mallet, B Pignon, Caroline Barau, A Vehier, C Lançon, Myrtille André, Jasmina Mallet, Baptiste Pignon, H Yazbek, Julie Clauss-Kobayashi, Christine Passerieux, J M Dorey, Caroline Dubertret, Sylvain Leignier, K Souryis, P Peri, Isabelle Chereau, F Berna, O Blanc, G Chesnoy-Servanin, S Pires, D Lacelle, A Deloge, Franck Schürhoff, Hakim Laouamri, P M Llorca, O Godin, Bruno Aouizerate, C. Portalier, Pierre-Michel Llorca, R Rey, A Zinetti-Bertschy, H Denizot, Mathieu Urbach, M Jarroir, V Barteau, C Roman, B Aouizerate, C Passerieux, S Esselin, R M Honciuc, C Dubertret, Christophe Lançon, H. Laouamri, F Vaillant, Andrei Szöke, E Metairie, Marion Leboyer, Ching-lieng Lu, M Urbach, Fabrice Berna, C Faget, Romain Rey, Ophélia Godin, E Haffen, M Leboyer, D Capdevielle, Delphine Capdevielle, Thierry D′Amato, S Bensalem, and Emilie Terro

Subjects
profile, medicine.medical_specialty, AcademicSubjects/MED00800, clozapine, Positive and Negative Syndrome Scale, immuno-inflammatory, Schizophrenia (object-oriented programming), treatment-resistant, 030227 psychiatry, schizophrenia, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Immune system, signatures, medicine, Treatment resistant schizophrenia, Psychology, Psychiatry, 030217 neurology & neurosurgery, Clozapine, Regular Articles, medicine.drug
Abstract

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.

Published
2021
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31. Childhood Trauma increases suicidal behaviour in a treatment-resistant depression population: a FACE-DR report

Author

Antoine Yrondi, Guillaume Vaiva, Michel Walter, Thierry D Amato, Frank Bellivier, Djamila Bennabi, Thierry Bougerol, Vincent Camus, Olivier Doumy, Jean-Baptiste Genty, Emmanuel Haffen, Jérôme Holtzmann, Mathilde Horn, Christophe Lançon, Marion Leboyer, Pierre-Michel Llorca, Julia Maruani, Rémi Moirand, Fanny Molière, Jean Petrucci, Raphaelle Richieri, Ludovic Samalin, Laurent Schmitt, Florian Stephan, Philippe Courtet, Wissam El-Hage, Bruno Aouizerate, B. Aouizerate, D. Bennabi, M. Leboyer, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, H. Laouamri, Karmene Souryis, L. Mallet, L. Yon, J. Petrucci, J.B. Genty, A. Yrondi, D. Pierre, L. Schmitt, M. Sarrail, I. Ryff, E. Beuchet, G. Tio, C. Cappe, E. Clerc, M. Garnier, R.M. Honciuc, E. Allauze, O. Blanc, F. Bellivier, N. Allaili, I. Nieto, J. Meheust, Y. Sunthavy, J. Maruani, T. Bougerol, M. Polosan, P. Courvoisier, J. Holtzmann, B. Fredembach, S. Foubert-Andreani, V. Camus, W. El Hage, T. D’Amato, F. Haesebaert, C. Dubien, M. Lefebvre, A. Meznad, J. Brunelin, R. Moirand, O. Doumy, C. Lancon, R. Richieri, P. Peri, M. Faugere, C. Faget-Agius, P. Courtet, J.P. Boulenger, F. Moliere, F. Stephan, M. Walter, C. Mesmeur, G. Vaiva, M. Horn, Fondation FondaMental [Créteil], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital de Bohars - CHRU Brest (CHU - BREST ), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Henri Mondor, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier Charles Perrens [Bordeaux], CHU Henri Mondor [Créteil], CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Depressive disorders, MESH: Depression, MESH: Violence, Population, Poison control, Violence, Suicide prevention, Childhood trauma, MESH: Depressive Disorder, Treatment-Resistant, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Rating scale, Surveys and Questionnaires, Humans, Medicine, MESH: Surveys and Questionnaires, Risk factor, education, Suicidal ideation, Childhood neglect, Biological Psychiatry, education.field_of_study, MESH: Humans, MESH: Suicidal Ideation, Depression, business.industry, Childhood abuse, CTQ tree, 3. Good health, 030227 psychiatry, Suicide, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Treatment-resistant depression, medicine.symptom, Columbia Suicide Severity Rating Scale, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

International audience; Objective: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations.Methods: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively.Results: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores.Conclusion: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.

Published
2021
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32. Author response for 'Non‐Alcoholic Fatty Liver Disease in a sample of individuals with Bipolar Disorders: Results From the FACE‐BD Cohort'

Author

null Ophelia Godin, null Marion Leboyer, null Raoul Belzeaux, null Frank Bellivier, null Joséphine Loftus, null Philippe Courtet, null Caroline Dubertret, null Sebastien Gard, null Chantal Henry, null Pierre‐Michel Llorca, null Raymund Schwan, null Christine Passerieux, null Mircea Polosan, null Ludovic Samalin, null Emilie Olié, null Bruno Etain, null B. Etain, null C. Henry, null E. Olié, null M. Leboyer, null E. Haffen, null PM Llorca, null V. Barteau, null S. Bensalem, null O. Godin, null H. Laouamri, null K. Souryis, null H Mondor, null S. Hotier, null A. Pelletier, null N. Drancourt, null JP. Sanchez, null E. Saliou, null C. Hebbache, null J. Petrucci, null L. Willaume, null E. Bourdin, null F. Bellivier, null M. Carminati, null J. Maruani, null E. Marlinge, null M. Meyrel, null B. Antoniol, null A. Desage, null S. Gard, null A. Jutant, null K. Mbailara, null I. Minois, null L. Zanouy, null L. Bardin, null A. Cazals, null P. Courtet, null B. Deffinis, null D. Ducasse, null M. Gachet, null A. Henrion, null F. Molière, null B. Noisette, null G. Tarquini, null R. Belzeaux, null N. Correard, null F. Groppi, null A. Lefrere, null L. Lescalier., null E. Moreau, null J. Pastol, null M. Rebattu, null B. Roux, null N. Viglianese, null R. Cohen, null J.P. Kahn, null M. Milazzo, null O. Wajsbrot‐Elgrabli, null T. Bougerol, null B. Fredembach, null A. Suisse, null B. Halili, null A Pouchon, null M. Polosan, null A.M. Galliot, null I. Grévin, null A.S. Cannavo, null N. Kayser, null C. Passerieux, null P. Roux, null V. Aubin, null I. Cussac, null M.A Dupont, null J. Loftus, null I. Medecin, null C. Dubertret, null N. Mazer, null C. Portalier, null C. Scognamiglio, and null A. Bing

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Cohort, Fatty liver, Medicine, Non alcoholic, Sample (statistics), Disease, business, medicine.disease
Published
2020
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33. Minimum clinically important differences for the Functioning Assessment Short Test and a battery of neuropsychological tests in bipolar disorders: results from the FACE-BD cohort

Author

Caroline Dubertret, P. Courtet, Mickael Ehrminger, Eric Brunet-Gouet, Paul Roux, Franck Bellivier, Jean-Pierre Kahn, Thierry Bougerol, Emilie Olié, Bruno Etain, Christine Passerieux, Bruno Aouizerate, M. Leboyer, Valerie Aubin, J.M. Azorin, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Fondation FondaMental [Créteil], Centre hospitalier Charles Perrens [Bordeaux], Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Département de Psychiatrie et de Médecine Addictologique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation Santé des Etudiants de France, Université de Lorraine (UL), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Psychiatrie Translationnelle (Equipe 15), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), HAL UVSQ, Équipe, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Cohortes - FondaMental-Cohortes - - Psy-COH2010 - ANR-10-COHO-0010 - COHO - VALID, Hôpital Charles Perrens, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Male, cognition, medicine.medical_specialty, Bipolar Disorder, Epidemiology, [SDV]Life Sciences [q-bio], Global Assessment of Functioning, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Neuropsychological Tests, working memory, memory, 03 medical and health sciences, Executive Function, 0302 clinical medicine, Physical medicine and rehabilitation, minimal clinical important differences, mental disorders, Outcome Assessment, Health Care, medicine, Reaction Time, Humans, Attention, 030212 general & internal medicine, Social Behavior, business.industry, Minimal clinically important difference, Public Health, Environmental and Occupational Health, Neuropsychology, speed processing, Cognition, Original Articles, Executive functions, executive functions, humanities, 030227 psychiatry, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Standard error, Cross-Sectional Studies, Memory, Short-Term, social functioning, bipolar disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Observational study, Female, business, Cognition Disorders
Abstract

Aims Establishing the minimum clinically important difference (MCID) in functioning and cognition is essential to the interpretation of the research and clinical work conducted in bipolar disorders (BD). The present study aimed to estimate the MCID for the Functioning Assessment Short Test (FAST) and a battery of neuropsychological tests in BD. Methods Anchor-based and distributive methods were used to estimate the MCID for the FAST and cognition using data from a large, multicentre, observational cohort of individuals with BD. The FAST and cognition were linked with the Clinical Global Impressions Scale-Severity (CGI-S) and Global Assessment of Functioning (GAF) using an equipercentile method. The magnitude of the standard error measurement (s.e.m.) provided another estimate of the MCID. Results In total, 570 participants were followed for 2 years. Cross-sectional CGI-S and GAF scores were linked to a threshold ⩽7 on the FAST for functional remission. The MCID for the FAST equalled 8- or 9-points change from baseline using the CGI-S and GAF. One s.e.m. on the FAST corresponded to 7.6-points change from baseline. Cognitive variables insufficiently correlated with anchor variables (all ρ s.e.m. for cognitive variables corresponded to a range of 0.45 to 0.93-s.d. change from baseline. Conclusions These findings support the value of the estimated MCID for the FAST and cognition and may be a useful tool to evaluate cognitive and functional remediation effects and improve patient functional outcomes in BD. The CGI-S and GAF were inappropriate anchors for cognition. Further studies may use performance-based measures of functioning instead.

Published
2020
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34. Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review

Author

A, Chevance, D, Gourion, N, Hoertel, P-M, Llorca, P, Thomas, R, Bocher, M-R, Moro, V, Laprévote, A, Benyamina, P, Fossati, M, Masson, E, Leaune, M, Leboyer, and R, Gaillard

Subjects
Mental Health Services, Hospitals, Psychiatric, Suicide Prevention, Substance-Related Disorders, Pneumonia, Viral, Aftercare, Comorbidity, Antiviral Agents, Vulnerable Populations, Stress Disorders, Post-Traumatic, Betacoronavirus, Arts and Humanities (miscellaneous), Risk Factors, Humans, Drug Interactions, Child, Epidemics, Pandemics, Aged, Patient Care Team, Aged, 80 and over, Infection Control, SARS-CoV-2, Prisoners, Mental Disorders, Age Factors, COVID-19, Continuity of Patient Care, Suicide, Psychiatry and Mental health, Mental Health, Psychotic Disorders, Quarantine, Patient Compliance, France, Cognition Disorders, Coronavirus Infections, Hospital Units, Stress, Psychological
Abstract

The lack of ressources and coordination to face the epidemic of coronavirus raises concerns for the health of patients with mental disorders in a country where we keep in memory the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims at proposing guidance to ensure mental health care during the SARS-CoV epidemy in France.Authors performed a narrative review identifying relevant results in the scientific and medical literature and local initiatives in France.We identified four types of major vulnerabilities in patients suffering from mental disorders during this pandemic: (1) medical comorbidities that are more frequently found in patients suffering from mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which represent risk factors for severe infections with Covid-19; (2) age (the elderly constituting the population most vulnerable to coronavirus); (3) cognitive and behavioral troubles which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability due to stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly adapted to psychiatric establishments in a context of major shortage of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds are closed, wards have a high density of patients, mental health community facilities are closed, medical teams are understaffed and poorly trained to face infectious diseases. We could also face major issues in referring patients with acute mental disorders to intensive care units. To maintain continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of Covid+ units. These units are under the dual supervision of a psychiatrist and of an internist/infectious disease specialist; all new entrants should be placed in quarantine for 14 days; the nurse staff should benefit from specific training, from daily medical check-ups and from close psychological support. Family visits would be prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management should be organized with the possibility of home visits, in order to support them when they get back home and to help them to cope with the experience of confinement, which is at risk to induce recurrences of mental disorders. The total or partial closure of mental health community facilities is particularly disturbing for patients but a regular follow-up is possible with telemedicine and should include the monitoring of the suicide risk and psychoeducation strategies; developing support platforms could also be very helpful in this context. Private psychiatrists have also a crucial role of information with their patients on confinement and barrier measures, but also on measures to prevent the psychological risks inherent to confinement: maintenance of sleep regularity, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic.French mental healthcare is now in a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the containment of the general population.

Published
2020
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35. [Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks?]

Author

W, El-Hage, C, Hingray, C, Lemogne, A, Yrondi, P, Brunault, T, Bienvenu, B, Etain, C, Paquet, B, Gohier, D, Bennabi, P, Birmes, A, Sauvaget, E, Fakra, N, Prieto, S, Bulteau, P, Vidailhet, V, Camus, M, Leboyer, M-O, Krebs, and B, Aouizerate

Subjects
Infectious Disease Transmission, Patient-to-Professional, Attitude of Health Personnel, Health Personnel, Pneumonia, Viral, Workload, Anxiety, Severe Acute Respiratory Syndrome, Stress Disorders, Post-Traumatic, Betacoronavirus, Helplessness, Learned, Risk Factors, Work Schedule Tolerance, Adaptation, Psychological, Humans, Health Workforce, Burnout, Professional, Pandemics, Depression, SARS-CoV-2, Protective Devices, Uncertainty, COVID-19, Social Support, Resilience, Psychological, Behavior, Addictive, Occupational Diseases, Suicide, France, Coronavirus Infections, Delivery of Health Care, Influenza Pandemic, 1918-1919
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic.Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms.The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications.In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.

Published
2020

38. Comparison of three scales (BIS, SUMD and BCIS) for measuring insight dimensions and their evolution after one-year of follow-up: Findings from the FACE-SZ Cohort

Author

Delphine Capdevielle, Joanna Norton, Bruno Aouizerate, Fabrice Berna, Isabelle Chereau, Thierry D'Amato, Caroline Dubertret, Julien Dubreucq, Guillaume Fond, Lançon C, Jasmina Mallet, David Misdrahi, Catherine Passerieux, Romain Rey, Franck Schurhoff, Mathieu Urbach, Pierre-Michel Llorca, Stéphane Raffard, B. Aouizerate, F. Berna, O. Blanc, D. Capdevielle, I. Chereau-Boudet, N. Coulon, T. D'Amato, J.M. Dorey, C. Dubertret, G. Fond, F. Gabayet, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, P.M. Llorca, J. Mallet, E. Metairie, D. Misdrahi, C. Passerieux, B. Pignon, P. Peri, C. Portalier, R. Rey, C. Roman, F. Schürhoff, A. Szöke, M. Urbach, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Neuropsychologie Cognitive et Physiophatologie de la Schizophrénie (Inserm U1114 - UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Clermont-Ferrand, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paul-Valéry - Montpellier 3 (UPVM), This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut National de la Santé et de la Recherche Médicale)., Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Psychometrics, Composite score, [SDV]Life Sciences [q-bio], Clinical state, Cognitive Insight, 03 medical and health sciences, Cognitive dimensions of notations, 0302 clinical medicine, medicine, Humans, Biological Psychiatry, Psychiatric Status Rating Scales, Cognition, Awareness, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, Clinical Insight, Schizophrenia, Cohort, Schizophrenic Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Insight, Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Treatment need, Clinical psychology
Abstract

International audience; The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.

Published
2021
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39. [Is the medication reconciliation achievable and relevant in Psychiatry?: Feedback on the implementation of medication reconciliation on hospital admission]

Author

A, Leherle, C, Kowal, Z, Toulemon, M, Dalle-Pecal, A, Pelissolo, M, Leboyer, M, Paul, and C, Diviné

Subjects
Psychiatry, Psychotropic Drugs, Medication Reconciliation, Patient Admission, Involuntary Commitment, Mental Disorders, Humans, Medication Errors, Prospective Studies, Pharmacists, Pharmacy Service, Hospital, Feedback
Abstract

The health care pathway of patients suffering from mental disorders is complex and includes a risk of interruption of treatment. We implemented medication reconciliation at patients' admission to mental health care service in February 2017. The aim of this study was to achieve a feedback experience answering our questions about the feasibility and relevance of this process.A prospective analysis of medication reconciliations over the first 7 months of implementation was carried out according to 3 activity indicators and 6 performance indicators.A total of 39 patients were reconciled and 56.4 % of them were in enforced hospitalization unit. All patients were interviewed by the pharmacist. Collected information during this interview was concordant with at least one of the other sources in 70.4 % of the cases. Thirteen patients were not reconciled within 72h after their admission because of their psychiatric pathology. The average number of unintentional medication discrepancy (UMD) detected was 0.97 per reconciled patient. The rate of major gravity UMD was 23.7 %. The number of UMDs per patient was significantly higher in enforced hospitalization unit (P0.05). UMDs were essentially related to somatic drugs (81.6 %). Nearly 95 % of the detected UMDs resulted in a modification of prescription.These results show that medication reconciliation at patients' admission is feasible and relevant in psychiatry. To limit constraints related to psychiatric pathology, we propose to perform medication reconciliation of patients more than 72 hours after patient admission provided that their clinical condition allows it.

Published
2019

40. Activation Levels, Cardiovascular Risk, and Functional Impairment in Remitted Bipolar Patients: Clinical Relevance of a Dimensional Approach

Author

Jean-Pierre Kahn, Aubin, P. Courtet, Bruno Etain, Dargél Aa, Paul Roux, Stevenn Volant, Jan Scott, Chantal Henry, S Gard, Frank Bellivier, J.M. Azorin, R. Grant, M. Leboyer, Sukanta Saha, Thierry Bougerol, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU - Hôpital Bellevue, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Fondation FondaMental [Créteil], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Center for Global Health Research and Education - Centre pour la Recherche et la Formation en Santé Mondiale (CGH), Institut Pasteur [Paris]-Réseau International des Instituts Pasteur (RIIP), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Charles Perrens, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Princesse Grace [Monaco], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Newcastle University [Newcastle], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Pasteur [Paris] (IP)-Réseau International des Instituts Pasteur (RIIP), and Centre hospitalier Charles Perrens [Bordeaux]

Subjects
Male, Oncology, MESH: Bipolar Disorder/classification, MESH: Cognitive Dysfunction/physiopathology, MESH: Remission Induction, Bipolar Disorder, Functional impairment, Emotions, Activation level, Severity of Illness Index, Machine Learning, 0302 clinical medicine, Cluster Analysis, Medicine, Applied Psychology, ComputingMilieux_MISCELLANEOUS, MESH: Middle Aged, MESH: Risk, MESH: Machine Learning, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Remission Induction, General Medicine, Middle Aged, Psychiatry and Mental health, Clinical Psychology, Cardiovascular Diseases, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Adult, Risk, medicine.medical_specialty, MESH: Cognitive Dysfunction/etiology, MESH: Cardiovascular Diseases/physiopathology, MESH: Emotions/physiology, MESH: Bipolar Disorder/physiopathology, 03 medical and health sciences, MESH: Cross-Sectional Studies, Internal medicine, MESH: Severity of Illness Index, Humans, Cognitive Dysfunction, Clinical significance, MESH: Bipolar Disorder/complications, MESH: Humans, business.industry, MESH: Adult, Cardiovascular risk, MESH: Cluster Analysis, MESH: Male, 030227 psychiatry, Cross-Sectional Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; Letter to the Editor

Published
2019
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41. The 10-year findings from the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ): Review and recommendations for clinical practice

Author

F. Schürhoff, G. Fond, F. Berna, E. Bulzacka, O. Godin, L. Boyer, D. Misdrahi, M. Andrianarisoa, L. Brunel, N. Coulon, B. Aouizerate, D. Capdevielle, I. Chereau, T. D’Amato, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, J. Mallet, R. Rey, C. Lancon, C. Passerieux, A. Schandrin, M. Urbach, P. Vidailhet, M. Leboyer, P.M. Llorca, N. Bazin, O. Blanc, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M. Jarroir, D. Lacelle, C. Lançon, H. Laouamri, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, L. Ramet, C. Roman, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Université de Strasbourg (UNISTRA), Institut Européen des membranes (IEM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, CCSD, Accord Elsevier, Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Clermont Université-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, Psychopathologie et pharmacologie de la cognition, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], and CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA)

Subjects
Inflammation, Depression, [SDV]Life Sciences [q-bio], Dépression, Syndrome métabolique, Centre expert, Metabolic syndrome, 3. Good health, 030227 psychiatry, Expert centre, Treatment, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Cognition, Arts and Humanities (miscellaneous), [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Schizophrénie, Traitement, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Objectives The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. Methods More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. Results The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset < 19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. Conclusions In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.; Objectifs Le présent article propose de faire un retour sur les 10 ans d’expérience du réseau national des 10 centres experts schizophrénie Français, à travers une revue des principales publications scientifiques qui en sont issues. Méthodes À ce jour, les données de plus de 700 patients ont pu être analysées. Globalement, cette population est composée de trois quarts d’hommes, est âgée en moyenne de 32 ans, la durée moyenne de maladie est d’environ 11 ans, l’âge moyen de début de maladie est de 21 ans, la durée de psychose non traitée est d’environ un an et demi. 55 % des sujets sont consommateurs de tabac au moment de l’évaluation. Enfin, un focus sera fait sur les projets de recherche multicentriques collaboratifs déployés au sein de ce réseau. Résultats Les principales données obtenues peuvent être résumées comme suit : le syndrome métabolique reste deux fois plus fréquent dans la schizophrénie qu’en population générale et n’est pas correctement pris en charge ; des troubles cognitifs spécifiques ont été identifiés chez les patients consommateurs de benzodiazépines et chez les patients présentant une inflammation périphérique. Des spécificités liées au sexe ont également été observées ; la dépression comorbide reste très fréquente, elle est associée à une diminution de la qualité de vie et à une augmentation de la dépendance nicotinique chez les fumeurs. Prendre en charge la dépression et les symptômes négatifs pourraient fortement améliorer la qualité de vie des patients ; le délai à l’instauration du traitement est plus long pour les schizophrénies se déclenchant avant 19 ans et chez les consommateurs de cannabis. L’adhésion au traitement est diminuée chez les patients rapportant un ressenti subjectif négatif du traitement, indépendamment de la prise de poids ou d’un syndrome extrapyramidal. Enfin, l’akathisie est très fréquente et fortement associée à la polythérapie antipsychotique. Conclusions Ces résultats conduisent à formuler plusieurs recommandations. Le dépistage du trouble et le traitement devraient être renforcés chez les adolescents et les consommateurs de cannabis. Tous les patients devraient bénéficier d’une évaluation neuropsychologique au début de leur trouble, après stabilisation sous traitement, puis de façon plus espacée au cours de leur suivi. La prise en charge des paramètres métaboliques, de l’alimentation et de l’activité physique devrait être renforcée. La balance bénéfice/risque de la prescription de benzodiazépines doit être réévaluée régulièrement au regard de son impact notamment sur la cognition. La monothérapie antipsychotique est recommandée autant que possible pour limiter les effets indésirables. La dépression reste sous-diagnostiquée et doit faire l’objet d’une évaluation systématique et d’un traitement spécifique. La remédiation cognitive doit également être plus largement proposée chez les patients présentant des troubles cognitifs.

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2019
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42. Additional file 2: of Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental

Author

D. Bennabi, T. Charpeaud, A. Yrondi, J.-B. Genty, S. Destouches, S. Lancrenon, N. Alaïli, F. Bellivier, T. Bougerol, V. Camus, J.-M. Dorey, O. Doumy, F. Haesebaert, J. Holtzmann, C. LançOn, M. Lefebvre, F. Moliere, I. Nieto, C. Rabu, R. Richieri, L. Schmitt, F. Stephan, G. Vaiva, M. Walter, M. Leboyer, W. El-Hage, P.-M. Llorca, P. Courtet, B. Aouizerate, and E. Haffen

Abstract

Questionnaire. (DOCX 1090 kb)

Published
2019
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43. Relationship between childhood trauma and level of insight in schizophrenia: A path-analysis in the national FACE-SZ dataset

Author

Baptiste Pignon, Mohamed Lajnef, Ophélia Godin, Marie-Maud Geoffray, Romain Rey, Jasmina Mallet, Caroline Dubertret, Paul Roux, Christine Passerieux, Laurent Marulaz, Lore Brunel, Julien Dubreucq, Sylvain Leignier, Delphine Capdevielle, Myrtille André, Bruno Aouizerate, David Misdrahi, Fabrice Berna, Pierre Vidailhet, Isabelle Chereau, Pierre-Michel Llorca, Guillaume Fond, Christophe Lançon, Marion Leboyer, Franck Schürhoff, M.D. Andrianarisoa, B. Aouizerate, F. Berna, O. Blanc, L. Brunel, E. Bulzacka, D. Capdevielle, I. Chereau-Boudet, G. Chesnoy-Servanin, Jm Danion, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, C. Fluttaz, G. Fond, S. Fonteneau, F. Gabayet, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, P.M. Llorca, J. Mallet, E. Metairie, D. Misdrahi, I. Offerlin-Meyer, C. Passerieux, P. Peri, S. Pires, C. Portalier, R. Rey, C. Roman, M. Sebilleau, A. Schandrin, F. Schurhoff, A. Tessier, Am Tronche, M. Urbach, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Pôle de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Fondation FondaMental [Créteil], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier le Vinatier [Bron], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Pôle de Psychiatrie [Hôpital Henri Mondor], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital H. Mondor - A. Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS), Université Grenoble Alpes (UGA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Institut National des Sciences Appliquées (INSA), Assistance Publique-Hôpitaux de Marseille (AP-HM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées, Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)

Subjects
Adult, Male, Adolescent, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Psychological Trauma, Neglect, Diagnostic Self Evaluation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Adverse Childhood Experiences, Humans, Medicine, Path analysis (statistics), Psychological abuse, Biological Psychiatry, Physical neglect, ComputingMilieux_MISCELLANEOUS, media_common, business.industry, Adult Survivors of Child Abuse, CTQ tree, Awareness, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, Physical abuse, Adult Survivors of Child Adverse Events, Psychotic Disorders, Sexual abuse, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Female, business, 030217 neurology & neurosurgery, Psychopathology, Clinical psychology
Abstract

Introduction This study aimed was to investigate the relationship between different types of childhood trauma and the level of insight (i.e., awareness of having a psychiatric disorder) in subjects suffering from schizophrenia, as well as the putative role of clinical mediators. Methods 294 community-dwelling subjects with stable schizophrenia were included into FACE-SZ, a multicentre cross-sectional study. All patients were assessed by specialized multidisciplinary teams. The level of insight was assessed by the Scale to assess Unawareness of Mental Disorder (SUMD), and childhood trauma by the Childhood Trauma Questionnaire (CTQ). Path analyses from the five CTQ subscales (physical abuse and neglect, emotional abuse and neglect, and sexual abuse) and the SUMD, with current symptomatology (i.e., positive, negative, global psychopathology and depression) as mediator, was performed. Results Physical neglect (β = 0.14) and abuse (β = 0.13) were significantly associated with poor insight. Negative symptoms were a clinical mediator of the relationship between physical neglect and poor insight. Moreover, positive (β = 0.21) and negative (β = 0.30) symptoms were associated with poor insight, whereas depression (β = −0.14) was associated with higher levels of insight. Discussion For the first time, this study shows a significant relationship between childhood trauma, specifically physical neglect and abuse, and poor insight. The level of insight was linked to different clinical dimensions. Among subjects with schizophrenia, these results provide support for a role of childhood trauma in poorer management outcomes, and the need to provide treatment, including psycho-education that better targets the consequences of childhood trauma.

Published
2019
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44. Additional file 3: of Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental

Author

D. Bennabi, T. Charpeaud, A. Yrondi, J.-B. Genty, S. Destouches, S. Lancrenon, N. Alaïli, F. Bellivier, T. Bougerol, V. Camus, J.-M. Dorey, O. Doumy, F. Haesebaert, J. Holtzmann, C. LançOn, M. Lefebvre, F. Moliere, I. Nieto, C. Rabu, R. Richieri, L. Schmitt, F. Stephan, G. Vaiva, M. Walter, M. Leboyer, W. El-Hage, P.-M. Llorca, P. Courtet, B. Aouizerate, and E. Haffen

Abstract

Definitions (According to the American College of Neuropsychopharmacology) [47]. (DOCX 14 kb)

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2019
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45. Additional file 4: of Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental

Author

D. Bennabi, T. Charpeaud, A. Yrondi, J.-B. Genty, S. Destouches, S. Lancrenon, N. Alaïli, F. Bellivier, T. Bougerol, V. Camus, J.-M. Dorey, O. Doumy, F. Haesebaert, J. Holtzmann, C. LançOn, M. Lefebvre, F. Moliere, I. Nieto, C. Rabu, R. Richieri, L. Schmitt, F. Stephan, G. Vaiva, M. Walter, M. Leboyer, W. El-Hage, P.-M. Llorca, P. Courtet, B. Aouizerate, and E. Haffen

Abstract

Antidepressant treatments classified according to the pharmacological profile. (DOCX 14 kb)

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2019
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46. Clinical characteristics of bipolar disorders with postpartum depressive onset

Author

Sarah Tebeka, Ophelia Godin, Nicolas Mazer, Frank Bellivier, Philippe Courtet, Bruno Etain, Sébastien Gard, Marion Leboyer, Pierre-Michel Llorca, Joséphine Loftus, Emilie Olié, Christine Passerieux, Mircea Polosan, Raymund Schwan, Raoul Belzeaux, Caroline Dubertret, B. Etain, C. Henry, E. Olié, M. Leboyer, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, O. Godin, H. Laouamri, K. Souryis, S. Hotier, A. Pelletier, N. Drancourt, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Willaume, E. Bourdin, F. Bellivier, M. Carminati, E. Marlinge, J. Meheust, B. Antoniol, A. Desage, S. Gard, A. Jutant, K. Mbailara, I. Minois, L. Zanouy, C. Abettan, L. Bardin, A. Cazals, P. Courtet, B. Deffinis, D. Ducasse, M. Gachet, A. Henrion, E. Martinerie, F. Molière, B. Noisette, G. Tarquini, J.M. Azorin, R. Belzeaux, N. Correard, J.L. Consoloni, F. Groppi, L. Lescalier, J. Montant, M. Rebattu, N. Viglianese, R. Cohen, J.P. Kahn, M. Milazzo, O. Wajsbrot-Elgrabli, T. Bougerol, B. Fredembach, A. Suisse, B. Halili, A. Pouchon, M. Polosan, A.M. Galliot, I. Grévin, A.S. Cannavo, N. Kayser, C. Passerieux, P. Roux, V. Aubin, I. Cussac, M.A. Dupont, J. Loftus, I. Medecin, C. Dubertret, N. Mazer, C. Portalier, C. Scognamiglio, A. Bing, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation FondaMental, Institut National de la Santé et de la Recherche Médicale, Assistance Publique - Hôpitaux de Paris, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), and ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010)

Subjects
Adult, Postpartum depression, Pediatrics, medicine.medical_specialty, Bipolar Disorder, medicine.drug_class, Suicide, Attempted, Depression, Postpartum, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Bipolar disorder, Major depressive episode, Biological Psychiatry, Retrospective Studies, Pharmacology, Suicide attempt, business.industry, Mood stabilizer, Middle Aged, medicine.disease, Family life, 030227 psychiatry, 3. Good health, Cross-Sectional Studies, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, France, medicine.symptom, business, Postpartum period
Abstract

Background Postpartum period is associated with an increased risk of bipolar disorder diagnosis and relapse, mainly major depressive episode. Onset during this period might be associated with specific characteristics. Aim To compare the socio-demographic and clinical characteristics of parous women presenting with bipolar disorder and an index depressive episode occurring during or outside the postpartum period. Methods Using the multicenter cohort FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders), we considered all women who started their BD with a major depressive episode and have at least one child. We compared two groups depending on the onset: in or outside the postpartum period. Results Among the 759 women who started BD with a major depressive episode, 93 (12.2%) had a postpartum onset, and 666 (87.8%) had not. Women who started BD in the postpartum period with a major depressive episode have a more stable family life, more children, an older age at onset, more Bipolar 2 disorder, less history of suicide attempts, less depressive episodes and more mood stabilizer treatments as compared to those who started with a major depressive episode outside the postpartum period. The multivariable logistic regression showed that women with an onset in the postpartum period had significantly more children, less lifetime depressive episodes and a lower rate of history of suicide attempts as compared to women with an onset outside the postpartum period. Discussion Our results suggest that women starting their BD with postpartum depression have a more favorable course of BD, especially less history of suicide attempt and less lifetime depressive episodes.

Published
2021
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47. P.117 Immunological profiling of psychotic patients with metabolic syndrome

Author

Susana Barbosa, Ophélia Godin, Nicolas Glaichenhaus, M. Foiselle, M. Leboyer, and Ryad Tamouza

Subjects
Pharmacology, Psychiatry and Mental health, Neurology, business.industry, Profiling (information science), Medicine, Pharmacology (medical), Neurology (clinical), Metabolic syndrome, Bioinformatics, business, medicine.disease, Biological Psychiatry
Published
2021
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48. Profil inflammatoire lié aux conduites suicidaires dans les troubles bipolaires

Author

M. Foiselle, C. Hebbache, M. Coyac, C. Barau, J.-R. Richard, R. Tamouza, M. Leboyer, and E. Darrau

Abstract

De nombreuses etudes ont montre des anomalies immuno-inflammatoires, et digestives (Severance et al., 2013, 2014) dans les troubles bipolaires. Cependant les donnees sont tres heterogenes, comme illustre par l’exemple de l’IL-6, retrouvee augmentee par Moddabernia et al. (2016), diminuee par Soderlund et al., et non modifiee par Munkholm et al. (2013), dans la bipolarite. Pour mieux prendre en compte l’heterogeneite des signatures immuno-inflammatoires des troubles bipolaires, la stratification des patients, sur la base de biomarqueurs clinicobiologiques, apparait etre un enjeu essentiel. Des marqueurs de l’inflammation ayant ete associes aux conduites suicidaires chez des patients souffrant de troubles bipolaires, nous avons choisi d’etudier les marqueurs de l’inflammation (IL-1B, 10, 15, 16, 17 et CRP) et de la permeabilite digestive (I-FABP, zonuline, LPS, calprotectine), ainsi que des auto-anticorps d’origine digestive, chez 163 patients souffrant de bipolarite stratifies en fonction de la presence (n = 58) ou de l’absence d’antecedents de tentative de suicide (n = 105), compares a 184 temoins. Nous avons replique les resultats de Keshri et al. (2018) et de Severance et al. (2013) mettant en evidence une inflammation peripherique (augmentation des IL-15 [pa = 6,6e-07], 16 [pa = 1,7e-09], et 17 [pa = 7,2e-03]), et une augmentation de la permeabilite et de l’inflammation digestive (augmentation de zonuline [p = 0,047], calprotectine [p = 2,7e-04], LPS [p = 0,043]), dans les troubles bipolaires. Nous avons montre un profil specifique chez les patients souffrant de troubles bipolaires ayant des antecedents de tentatives de suicide, marque par une diminution d’IL-16 (p = 0,041), une augmentation de la CRP (p = 0,054), et de la I-FABP (p = 0,056), et une diminution des anticorps diriges contre la transglutaminase neo-epitope microbienne (pa = 0,089), et le facteur intrinseque (p = 0,050). Nos analyses renforcent ainsi l’hypothese d’anomalies immuno-inflammatoires et digestives, dans les troubles bipolaires. Par ailleurs, nos resultats suggerent un profil specifique chez les patients souffrant de troubles bipolaires ayant des antecedents de tentatives de suicide.

Published
2019
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49. Âge au diagnostic chez les adultes présentant un trouble du spectre de l’autisme sans déficience intellectuelle

Author

Richard Delorme, Manuel Bouvard, C. Villalon, M. Leboyer, O. Godin, A. Amestoy, I. Scheid, Julien Dubreucq, and P. Atzori

Abstract

Objectif Les troubles du spectre de l’autisme (TSA) ne sont pas toujours reperes precocement, pouvant amener a un diagnostic tardif, parfois a l’âge adulte. Cela constitue un enjeu majeur de sante publique. Soixante pour cent des patients presentant un TSA n’ont pas de deficience intellectuelle. L’objectif de cette etude est d’evaluer l’âge au diagnostic des adultes atteints d’un TSA sans deficit intellectuel. L’objectif secondaire est de determiner les facteurs qui l’influencent. Methode Il s’agit d’une etude d’observation analytique, par etude de cohorte, multicentrique retrospective, s’etendant sur une periode de 10 ans, de septembre 2008 a mars 2018. Elle a ete realisee au sein des 4 centres experts TSA SDI de la Fondation FondaMental en France metropolitaine. Les criteres d’inclusion etaient : l’âge strictement superieur a 16 ans, la presence d’un TSA selon les criteres du DSM-5, l’absence de deficience intellectuelle, et la consultation dans l’un des 4 centres experts, avec l’evaluation par les outils d’entretien standardises ADOS et ADI-R, et par l’echelle de quotient intellectuel WAIS-IV. Resultats Deux cent quarante patients ont ete inclus, dont 74,38 % de sexe masculin. La moyenne d’âge au diagnostic etait de 20,6 ans ± 13,5 ans. Nous n’avons pas retrouve de differences significatives d’âge au diagnostic entre hommes et femmes. Parmi les differents facteurs etudies, ceux influencant significativement cet âge etaient : l’annee de naissance (avec un âge au diagnostic plus precoce chez les moins de 26 ans compare aux plus de 26 ans), l’intensite precoce des symptomes (mesuree avec l’ADI-R), et le QI (principalement l’indice de comprehension verbale et l’indice de vitesse de traitement). Chez les femmes, le principal facteur influencant l’âge au diagnostic etait le score de communication a l’ADOS. Conclusion L’etude que nous avons realisee constate un âge moyen au diagnostic de 20,6 ans. L’âge au diagnostic est positivement correle au QI. Il n’y a pas de difference statistiquement significative selon le genre dans notre etude. Chez les hommes, l’âge au diagnostic est inversement proportionnel avec la severite des symptomes precoces, et proportionnel au score du quotient intellectuel. L’etude revele un âge au diagnostic plus tardif chez les femmes ayant de meilleures capacites de communication. Les strategies de compensation chez les adultes TSA sans deficit intellectuel seraient interessantes a etudier comme facteur influencant l’âge au diagnostic.

Published
2019
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50. Psychoses auto-immunes : fait ou fiction ?

Author

L. Groc, T. Pollack, M. Leboyer, and U. Maskos

Abstract

L’importance des anomalies immuno-inflammatoires au cours des troubles psychotiques a ete clairement demontree au cours des dix dernieres annees. Un des elements qui a recu le plus d’interet recemment est le lien entre maladies auto-immunes et psychoses. Ce lien est mis en evidence par les etudes epidemiologiques qui demontrent la prevalence elevee de pathologies psychiatriques chez les patients atteints de maladies auto-immunes, par le terrain immunogenetique qui favorise la production d’autoanticorps, par la presence de marqueurs inflammatoires et surtout par la mise en evidence d’autoanticorps plasmatiques chez des patients psychotiques. Recemment, ont ete decouverts de nouveaux auto-anticorps diriges contre les recepteurs cerebraux dans des sous-groupes de patients schizophrenes ou psychotiques qui permettent d’esperer de mieux comprendre les causes de ces maladies, le developpement de marqueurs biologiques de stratification et surtout de nouvelles strategies therapeutiques. Laurent Groc (CNRS, universite de Bordeaux) decrira l’impact fonctionnel des auto-anticorps diriges contre les recepteurs NMDA issus de patients psychotiques. En particulier, l’impact moleculaire et cellulaire de ces autoanticorps sur la dynamique des recepteurs glutamatergiques et d’autres voies de signalisation (ex. dopamine) sera discute, en lien avec le deficit de plasticite synaptique observe avec ces autoanticorps. Il discutera de plus l’importance clinique de detecter a la fois la presence des autoanticorps ainsi que leur pathogenecite moleculaire, afin de permettre un meilleur diagnostic clinique et de mieux comprendre l’etiologie de ces pathologies. Uwe Maskos (Institut Pasteur, Paris) est a l’origine de la mise en evidence d’une nouvelle classe d’autoanticorps diriges contre le recepteur cholinergique, au niveau peripherique et central. Il detaillera la genese de cette auto-immunite a la suite a d’infections, les perspectives diagnostiques et therapeutiques. Thomas Pollak, psychiatre responsable d’une consultation specialisee pour le depistage des encephalites et des psychoses auto-immunes au Maudsley Institute a Londres, presentera les arguments cliniques devant lesquels nous devons chercher la presence de ces auto-anticorps. Il decrira les vignettes cliniques des patients porteurs d’autoanticorps diriges contre des recepteurs cerebraux et resumera les strategies therapeutiques immunomodulatrices utilisees chez ces patients.

Published
2019
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