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1. Determinants of Kidney Function and Accuracy of Kidney Microcysts Detection in Patients Treated With Lithium Salts for Bipolar Disorder

Author

Nahid Tabibzadeh, Anne-Laure Faucon, Emmanuelle Vidal-Petiot, Fidéline Serrano, Lisa Males, Pedro Fernandez, Antoine Khalil, François Rouzet, Coralie Tardivon, Nicolas Mazer, Caroline Dubertret, Marine Delavest, Emeline Marlinge, Bruno Etain, Frank Bellivier, François Vrtovsnik, and Martin Flamant

Subjects
nephrotoxicity, lithium, CKD-chronic kidney disease, kidney microcysts, bipolar disorder, Therapeutics. Pharmacology, RM1-950
Abstract

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection.Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences.Results: Median age was 51 [27–62] years, and median lithium treatment duration was 5 [2–14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β −0.8 [−1; −0.6] ml/min/1.73 m2 GFR decrease for each year of treatment), a higher age (β −0.4 [−0.6; −0.3] ml/min/1.73 m2 for each year of age, p < 0.001), albuminuria (β −3.97 [−6.6; −1.3], p = 0.003), hypertension (β −6.85 [−12.6; −1.1], p = 0.02) and hypothyroidism (β −7.1 [−11.7; −2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = −0.64, p < 0.001), but not in patients with no microcysts (r = −0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR

Published
2022
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2. Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative

Author

Jan Scott, Diego Hidalgo-Mazzei, Rebecca Strawbridge, Allan Young, Matthieu Resche-Rigon, Bruno Etain, Ole A. Andreassen, Michael Bauer, Djamila Bennabi, Andrew M. Blamire, Fawzi Boumezbeur, Paolo Brambilla, Nadia Cattane, Annamaria Cattaneo, Marie Chupin, Klara Coello, Yann Cointepas, Francesc Colom, David A. Cousins, Caroline Dubertret, Edouard Duchesnay, Adele Ferro, Aitana Garcia-Estela, Jose Goikolea, Antoine Grigis, Emmanuel Haffen, Margrethe C. Høegh, Petter Jakobsen, Janos L. Kalman, Lars V. Kessing, Farah Klohn-Saghatolislam, Trine V. Lagerberg, Mikael Landén, Ute Lewitzka, Ashley Lutticke, Nicolas Mazer, Monica Mazzelli, Cristina Mora, Thorsten Muller, Estanislao Mur-Mila, Ketil Joachim Oedegaard, Leif Oltedal, Erik Pålsson, Dimitri Papadopoulos Orfanos, Sergi Papiol, Victor Perez-Sola, Andreas Reif, Philipp Ritter, Roberto Rossi, Thomas Schulze, Fanny Senner, Fiona E. Smith, Letizia Squarcina, Nils Eiel Steen, Pete E. Thelwall, Cristina Varo, Eduard Vieta, Maj Vinberg, Michele Wessa, Lars T. Westlye, and Frank Bellivier

Subjects
Bipolar, Precision, Personalization, Lithium, Response, Phenotype, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Abstract Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

Published
2019
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3. Current (but not ex) cigarette smoking is associated with worse cognitive performances in schizophrenia: results from the FACE-SZ cohort

Author

Jasmina, Mallet, Ophélia, Godin, Yecodji, Dansou, Nicolas, Mazer, Claire, Scognamiglio, Fabrice, Berna, Laurent, Boyer, Delphine, Capdevielle, Isabelle, Chéreau, Thierry, D'Amato, Julien, Dubreucq, Guillaume, Fond, Sylvain, Leigner, Pierre-Michel, Llorca, David, Misdrahi, Christine, Passerieux, Romain, Rey, Baptiste, Pignon, Mathieu, Urbach, Benoit, Schorr, Franck, Schürhoff, Le Strat, Yann, and Caroline, Dubertret

Subjects
Psychiatry and Mental health, Applied Psychology
Abstract

Background Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects. Methods In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used. Results In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41–0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001). Conclusions This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.

Published
2022

4. Handedness as a neurodevelopmental marker in schizophrenia: Results from the FACE-SZ cohort

Author

Jasmina, Mallet, Ophélia, Godin, Yann, Le Strat, Nicolas, Mazer, Fabrice, Berna, Laurent, Boyer, Delphine, Capdevielle, Julie, Clauss, Isabelle, Chéreau, Thierry, D'Amato, Julien, Dubreucq, Sylvain, Leigner, Pierre-Michel, Llorca, David, Misdrahi, Christine, Passerieux, Romain, Rey, Baptiste, Pignon, Mathieu, Urbach, Franck, Schürhoff, Guillaume, Fond, and Caroline, Dubertret

Subjects
Cohort Studies, Learning Disabilities, Schizophrenia, Humans, Functional Laterality, Psychomotor Agitation, Biomarkers
Abstract

High rates of non-right-handedness (NRH) including mixed-handedness have been reported in neurodevelopmental disorders. In schizophrenia (SZ), atypical handedness has been inconsistently related to impaired features. We aimed to determine whether SZ subjects with NRH and mixed-handedness had poorer clinical and cognitive outcomes compared to their counterparts.667 participants were tested with a battery of neuropsychological tests, and assessed for laterality using the Edinburg Handedness Inventory. Clinical symptomatology was assessed. Learning disorders and obstetrical complications were recorded. Biological parameters were explored.The prevalence of NRH and mixed-handedness was high (respectively, 42.4% and 34.1%). In the multivariable analyses, NRH was associated with cannabis use disorder (Non-right and mixed-handedness are very high in patients with SZ, possibly reflecting a neurodevelopmental origin. NRH is associated with learning disorders and cannabis use. Mixed-handedness is associated with positive symptoms, current depressive disorder, cannabis use and less akathisia. However, this study did not confirm greater cognitive impairment in these patients.

Published
2021

5. Determinants of Kidney Function and Accuracy of Kidney Microcysts Detection in Patients Treated With Lithium Salts for Bipolar Disorder

Author

Nahid Tabibzadeh, Anne-Laure Faucon, Emmanuelle Vidal-Petiot, Fidéline Serrano, Lisa Males, Pedro Fernandez, Antoine Khalil, François Rouzet, Coralie Tardivon, Nicolas Mazer, Caroline Dubertret, Marine Delavest, Emeline Marlinge, Bruno Etain, Frank Bellivier, François Vrtovsnik, Martin Flamant, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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, Nuclear Medicine Department [Hôpital Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Radiologie [Bichat] (DR- Bichat), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Fondation FondaMental [Créteil], Hopital Saint-Louis [AP-HP] (AP-HP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Gestionnaire, HAL Sorbonne Université 5

Subjects
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Pharmacology, CKD-chronic kidney disease, bipolar disorder, lithium, nephrotoxicity, kidney microcysts, Pharmacology (medical), Therapeutics. Pharmacology, RM1-950, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Original Research
Abstract

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection.Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences.Results: Median age was 51 [27–62] years, and median lithium treatment duration was 5 [2–14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β −0.8 [−1; −0.6] ml/min/1.73 m2 GFR decrease for each year of treatment), a higher age (β −0.4 [−0.6; −0.3] ml/min/1.73 m2 for each year of age, p < 0.001), albuminuria (β −3.97 [−6.6; −1.3], p = 0.003), hypertension (β −6.85 [−12.6; −1.1], p = 0.02) and hypothyroidism (β −7.1 [−11.7; −2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = −0.64, p < 0.001), but not in patients with no microcysts (r = −0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR 2 (AUC 0.893, p < 0.001, sensitivity 80%, specificity 81% for a cut-off value of five microcysts).Conclusion: Lithium treatment duration and hypothyroidism strongly impacted mGFR independently of age, especially in patients with microcysts. MRI might help detect early lithium-induced kidney damage and inform preventive strategies.

Published
2021

6. Kidney function and long-term treatment with lithium salts for bipolar disorder Determinants of mGFR and accuracy of kidney microcysts detection in the diagnosis of CKD

Author

Marine Delavest, Emmanuelle Vidal-Petiot, Frank Bellivier, François Rouzet, Emeline Marlinge, François Vrtovsnik, Nahid Tabibzadeh, Pedro Fernandez, A L Faucon, Fidéline Serrano, Lisa Males, Martin Flamant, Antoine Khalil, Nicolas Mazer, Coralie Tardivon, Bruno Etain, and Caroline Dubertret

Subjects
medicine.medical_specialty, Kidney, Lithium (medication), business.industry, Lithium carbonate, Urology, Renal function, medicine.disease, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, medicine, Albuminuria, Bipolar disorder, medicine.symptom, Stage (cooking), business, medicine.drug, Cohort study
Abstract

Background and objectivesKidney damage during early stages of lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection.Design, setting, participants and measurementsCross sectional cohort study. Systematic evaluation including mGFR of 217 consecutive adult patients treated with lithium carbonate. Kidney MRI imaging in 99 patients with half-Fourier turbo spinecho and Single-shot with long echo time sequences.ResultsMedian age was 51 [27-62] years, and median lithium treatment duration was 5 [2-14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β −0.8 [-1; - 0.6] ml/min/1.73m2GFR decrease for each year of treatment), a higher age (β −0.4 [-0.6; −0.3] ml/min/1.73m2for each year of age, p2(22%) had a higher prevalence and number of renal microcysts. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as one year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r=-0.64, p2(AUC 0.893, pConclusionsBesides usual risk factors of GFR decrease, lithium treatment duration strongly impacted mGFR independently of age, especially in patients with microcysts. Hypothyroidism was also negatively associated with kidney function in these patients. MRI might help detect early lithium-induced kidney damage and inform preventive strategies.

Published
2021

7. The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise

Author

Sébastien Guillaume, Marion Leboyer, Frank Bellivier, Katia M'Bailara, Georges Brousse, Isabelle Biseul, Nicolas Mazer, Emilie Olié, Philippe Courtet, Raymund Schwan, Joséphine Loftus, Valentin Flaudias, Sébastien Gard, Paul Roux, Ludovic Samalin, Ophélia Godin, Romain Icick, Iréna Cussac, Pierre-Michel Llorca, Bruno Etain, Mircea Polosan, Chantal Henry, Emmanuel Haffen, Valerie Aubin, Raoul Belzeaux, Fondation FondaMental [Créteil], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Charles Perrens [Bordeaux], CHU Clermont-Ferrand, Hôpital Princesse Grace [Monaco], 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, Centre Psychothérapique de Nancy [Laxou] (CPN), 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), [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), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], 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 BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoires de neurosciences intégratives et cliniques (EA 481), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), 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 de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Agence Nationale de la Recherche, ANR Assistance Publique - Hôpitaux de Paris, AP-HP, This research was supported by the Foundation FondaMental, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique des Hôpitaux de Paris (AP-HP), and by the Investissements d'Avenir program managed by the Agence National de la Recherche (ANR) under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. The funding sources had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Charles Perrens, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Psychothérapique de Nancy (CPN), Hôpital Lapeyronie [Montpellier] (CHU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut de Génomique Fonctionnelle (IGF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Bipolar Disorder, Alcohol use disorder, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Outpatients, medicine, Prevalence, Humans, Dual diagnosis, Bipolar disorder, Clinical trajectory, Sequence of onset, Sequence (medicine), business.industry, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Alcoholism, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Binary regression, business, 030217 neurology & neurosurgery
Abstract

International audience; Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD. Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first). Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p

Published
2020

8. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort

Author

Nicolas Mazer, Christine Passerieux, Bruno Etain, Valerie Aubin, S Gard, Joséphine Loftus, Raoul Belzeaux, Pierre-Michel Llorca, F Poinso, Thomas Schwitzer, Ludovic Samalin, Paul Roux, Bruno Aouizerate, A. Pelletier, Ophélia Godin, Emmanuel Haffen, Emilie Olié, Caroline Dubertret, Raymund Schwan, Marion Leboyer, C. Henry, P. Courtet, Thierry Bougerol, Franck Bellivier, Mircea Polosan, L Encely, Djamila Bennabi, Fondation FondaMental [Créteil], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, 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), Service de Psychiatrie et de Médecine Addictologique [AP-HP, GH Saint-Louis-Lariboisière-F.Widal], AP-HP Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal, GHU Paris Psychiatrie et Neurosciences, Service de Psychiatrie [CHU Mondor], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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 Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), 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), Centre Psychothérapique de Nancy-Unité D, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital psychiatrique de Nancy, 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), Hôpital Charles Perrens, Ministère des Affaires Sociales et de la Santé ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Assistance Publique - Hôpitaux de Paris, AP-HP, This multicenter, cross-sectional study included patients recruited into the FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders) cohort between June 2009 and June 2018. The FACE-BD cohort is based on a French national network of 12 BD Expert Centers (Besançon, Bordeaux, Clermont-Ferrand, Créteil, Colombes, Grenoble, Marseille, Monaco, Montpellier, Nancy, Paris and Versailles). This network was set up by the FondaMental Foundation ( www.fondation-fondamental.org ) and funded by the French Ministry of Research and the French Ministry of Health to build an infrastructure and to provide resources to follow clinical cohorts and comparative-effectiveness research on a patient population. This cohort and the clinical variables have been extensively described in a previous paper ( Henry et al., 2015 )., This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), by the Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program, 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). 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., Aix Marseille Université (AMU), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), and Centre hospitalier Charles Perrens [Bordeaux]

Subjects
Adult, Pediatrics, medicine.medical_specialty, Adolescent, Bipolar disorder, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Logistic regression, National cohort, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Anticonvulsant, Humans, 030212 general & internal medicine, Medical prescription, Women of childbearing age, ComputingMilieux_MISCELLANEOUS, Valproate, business.industry, Valproic Acid, Middle Aged, medicine.disease, 3. Good health, Affect, Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Childbearing age, Cohort, Female, business, 030217 neurology & neurosurgery
Abstract

International audience; Background: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. Methods: Based on a large national cohort, we included all BD women 16–50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. Results: Of the 1018 included women 16–50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p

Published
2020

9. Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative

Author

Diego Hidalgo-Mazzei, Matthieu Resche-Rigon, Fiona E. Smith, Cristina Mora, Aitana García-Estela, Maj Vinberg, Erik Pålsson, Adele Ferro, Andrew M. Blamire, Andreas Reif, Monica Mazzelli, Margrethe Collier Høegh, Eduard Vieta, Fawzi Boumezbeur, Caroline Dubertret, Petter Jakobsen, Edouard Duchesnay, Jan Scott, Klara Coello, Antoine Grigis, Thorsten Müller, Nicolas Mazer, Allan H. Young, Ole A. Andreassen, Nils Eiel Steen, Ketil J. Oedegaard, Peter E. Thelwall, Rebecca Strawbridge, Yann Cointepas, Letizia Squarcina, Frank Bellivier, Fanny Senner, Sergi Papiol, Farah Klöhn-Saghatolislam, David A. Cousins, Michael Bauer, Francesc Colom, Jose Manuel Goikolea, Emmanuel Haffen, Marie Chupin, Thomas G. Schulze, Ute Lewitzka, Bruno Etain, Annamaria Cattaneo, Lars Vedel Kessing, Lars T. Westlye, Michèle Wessa, Trine Vik Lagerberg, Ashley Lutticke, Paolo Brambilla, Philipp Ritter, C. Varo, Leif Oltedal, Nadia Cattane, Janos Kalman, Roberto Rossi, Dimitri Papadopoulos Orfanos, Víctor Pérez-Sola, Mikael Landén, Estanislao Mur-Mila, Djamila Bennabi, Newcastle University [Newcastle], Université Paris Diderot - Paris 7 (UPD7), King‘s College London, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint Louis [APHP]-Institut national du cancer [Boulogne] (INCA), Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Centre d'Investigation Clinique de Besançon (CICB), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang Bourgogne Franche-Comté-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CATI Multicenter Neuroimaging Platform (CATI), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Louis Mourier - AP-HP [Colombes], 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), Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité Analyse et Traitement de l'Information (UNATI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Max-Planck-Institut, This project has received funding from the European Union Horizon 2020 research and innovation program ((EU. 3.1.1. Understanding health, wellbeing and disease: Grant No 754907), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Centre de Psychiatrie et Neurosciences (U894), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), 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]), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
medicine.medical_specialty, Lithium (medication), [SDV]Life Sciences [q-bio], Psychological intervention, Omics, Neuroimaging, Review, Lithium, Digital, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, medicine, Prospective cohort study, Intensive care medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Personalization, business.industry, lcsh:QP351-495, Response, Actigraphy, Precision, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, lcsh:Neurophysiology and neuropsychology, Phenotype, Mood, Tolerability, Bipolar, Biomarker (medicine), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

Published
2019

10. Prevalence and correlates of psychotic-like experiences in the general population

Author

Sarah Tebeka, Caroline Dubertret, Nicolas Mazer, Yann Le Strat, Julie Bourgin, and Jasmina Mallet

Subjects
Adult, medicine.medical_specialty, Adolescent, Population, Comorbidity, Family income, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Epidemiology, medicine, Prevalence, Humans, education, Psychiatry, Biological Psychiatry, Aged, Aged, 80 and over, education.field_of_study, business.industry, Mental Disorders, Middle Aged, medicine.disease, Personality disorders, 030227 psychiatry, Psychiatry and Mental health, Mood, Cross-Sectional Studies, Psychotic Disorders, Anxiety, Female, France, Gradual increase, Substance use, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background To what extent Psychotic Like Experiences (PLEs) are associated with nonpsychotic psychiatric disorders and whether the number of PLEs is associated with higher rates of psychiatric disorders remains unclear. Methods The sample was composed of 34,653 civilian participants, aged 18 years and older from wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This was a representative sample of the non-institutionalized U.S. population. Twenty-two PLEs were assessed. Lifetime prevalence of psychiatric disorders (any mood, anxiety, substance use and personality disorders, PTSD, ADHD, and suicide attempts) according to the number of PLEs were calculated. Results Almost a third (26.69%) of respondents reported experiencing at least one type of PLEs. There was a gradual association between the number of PLEs and the presence of a nonpsychotic psychiatric disorder (ranging from 5.68%in participants with no PLEs up to 99.53% in those with five or more PLEs). This association with PLE was significant for each of the 25 psychiatric disorders examined regardless of the number of PLEs. Lifetime prevalence of PLEs were significantly higher among the younger respondents, women, non-married, unemployed, high educational level and those with low family income. Conclusion There is a gradual increase in the magnitude of the association of the numbers of PLEs for each of the 25 nonpsychotic psychiatric disorders examined. Having at least one PLE is strongly associated with the presence of a psychiatric disorder.

Published
2018

11. 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

12. Tobacco Smoking and Psychotic-Like Experiences in a General Population Sample

Author

Nicolas Mazer, Yann Le Strat, Caroline Dubertret, and Jasmina Mallet

Subjects
Male, medicine.medical_specialty, Psychosis, Cross-sectional study, Alcohol use disorder, 03 medical and health sciences, 0302 clinical medicine, Tobacco Smoking, medicine, Humans, 0501 psychology and cognitive sciences, Longitudinal Studies, 050102 behavioral science & comparative psychology, Subclinical infection, Psychiatric Status Rating Scales, Smokers, business.industry, Public health, 05 social sciences, Confounding, Non-Smokers, medicine.disease, Former Smoker, Health Surveys, United States, Psychiatry and Mental health, Cross-Sectional Studies, Psychotic Disorders, Schizophrenia, Female, Ex-Smokers, business, 030217 neurology & neurosurgery, Demography
Abstract

Objective Recent findings suggest an association between tobacco and psychosis, but whether this association is mediated by confounding factors is unknown. Psychosis-like experiences (PLEs) are a subclinical expression of psychosis. To disentangle the association of tobacco with PLEs, we examined data from a large US population-based, nationally representative sample. Methods Analysis was conducted on Wave 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (N = 34,653 adults, conducted from 2004 to 2005). Participants were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Twenty-two PLEs previously described as observed indicators of psychosis were used. Participants were stratified according to their smoking status (never/former/current) for 5 different types of tobacco. Results There was a significant association (ie, with 95% CIs for which the lower value was ≥ 1) between smoking status and 14 of the 22 assessed PLEs. These associations remained significant after adjustment for sociodemographic variables (including urbanicity or ethnicity), lifetime drug use disorder, and past-year cannabis use. While 26.33% of nonsmokers reported at least 1 PLE, this prevalence was slightly higher in former smokers (27.48%) and rose as high as 39.09% in current smokers (for current smokers vs lifetime abstainers, adjusted OR = 1.33; 95% CI, 1.23-1.45). All 22 PLEs had higher prevalence in smokers than in former smokers or lifetime abstainers. A total of 8.56% of smokers reported at least 5 PLEs, compared to 3.42% in lifetime abstainers (aOR = 1.56; 95% CI, 1.32-1.84). Conclusions In a large population-based, nationally representative sample, smoking status was associated with various PLEs. This association was not explained only by other known risk factors of PLEs or schizophrenia. There is a need to identify the potential neurobiological mechanisms by which smoking and PLEs are associated, for patients and from a public health perspective.

Published
2018

13. Tobacco smoking is associated with antipsychotic medication, physical aggressiveness, and alcohol use disorder in schizophrenia: results from the FACE-SZ national cohort

Author

Y. Le Strat, F. Gabayet, David Misdrahi, Nicolas Mazer, Pierre Vidailhet, C. Lançon, F. Schürhoff, M. Andrianarisoa, Guillaume Fond, Mathieu Urbach, Catherine Faget, Romain Rey, Bruno Aouizerate, Isabelle Chereau, Delphine Capdevielle, R. Honciuc, Julien Dubreucq, Thierry d'Amato, Fabrice Berna, A. Schandrin, Paul Roux, Caroline Dubertret, Lionel Brunel, C. Portalier, Pierre-Michel Llorca, Jasmina Mallet, 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), Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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 Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Scientifique et Technique du Bâtiment [Nantes] (CSTB), Centre Scientifique et Technique du Bâtiment (CSTB), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Mitsubishi Electric ITE-TCL, Université Montpellier 1 (UM1), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), ONERA - The French Aerospace Lab [Toulouse], ONERA, Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), 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), and Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)

Subjects
Male, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alcohol use disorder, Comorbidity, Childhood trauma, 0302 clinical medicine, Aggressiveness, Adverse Childhood Experiences, Medicine, Antipsychotics, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Univariate analysis, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Alcohol dependence, General Medicine, Middle Aged, 3. Good health, Aggression, Psychiatry and Mental health, Alcoholism, Adult Survivors of Child Adverse Events, Schizophrenia, Female, Antipsychotic Agents, Adult, medicine.medical_specialty, Population, National cohort, 03 medical and health sciences, Young Adult, Tobacco Smoking, Humans, Antipsychotic, Psychiatry, education, Biological Psychiatry, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, 030227 psychiatry, Mood, Cross-Sectional Studies, Psychotic Disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, 030217 neurology & neurosurgery
Abstract

International audience; Tobacco smoking is common in schizophrenia and is one of the main causes of premature mortality in this disorder. Little is known about clinical correlates and treatments associated with tobacco smoking in patients with schizophrenia. Still, a better characterization of these patients is necessary, in a personalized care approach. Aggressiveness and childhood trauma have been associated with tobacco smoking in general population, but this association has never been explored in schizophrenia. Our study examines the clinical and therapeutic characteristics of tobacco smoking in schizophrenia. 474 stabilized patients (mean age = 32.2; 75.7% male gender; smokers n = 207, 54.6%) were consecutively included in the network of the FondaMental Expert centers for Schizophrenia and assessed with valid scales. Current tobacco status was self-declared. Aggressiveness was self-reported with Buss-Perry Aggressiveness Questionnaire and Childhood Trauma with Childhood Trauma Questionnaire. Ongoing treatment was reported. In univariate analysis, tobacco smoking was associated with lower education level (p < 0.01), positive syndrome (p < 0.01), higher physical aggressiveness (p < 0.001), alcohol dependence (p < 0.001), and First Generation Antipsychotics (FGAs) use (p = 0.018). In a multivariate model, tobacco smoking remained associated with physical aggressiveness (p < 0.05), current alcohol dependence (p < 0.01) and FGA use (p < 0.05). No association was observed with childhood trauma history, mood disorder, suicidal behavior, psychotic symptom, global functioning or medication adherence. Patients with tobacco use present clinical and therapeutic specificities, questioning the neurobiological links between tobacco and schizophrenia. They could represent a specific phenotype, with specific clinical and therapeutic specificities that may involve interactions between cholinergic-nicotinic system and dopaminergic system. Further longitudinal studies are needed to confirm the potential efficacy of second generation antipsychotics (SGAs) on tobacco use in schizophrenia and to develop effective strategies for tobacco cessation in this population.

Published
2017

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