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1. Fasting upregulates the monocarboxylate transporter MCT1 at the rat blood-brain barrier through PPAR δ activation

Author: Stéphanie Chasseigneaux, Véronique Cochois-Guégan, Lucas Lecorgne, Murielle Lochus, Sophie Nicolic, Corinne Blugeon, Laurent Jourdren, David Gomez-Zepeda, Stefan Tenzer, Sylvia Sanquer, Valérie Nivet-Antoine, Marie-Claude Menet, Jean-Louis Laplanche, Xavier Declèves, Salvatore Cisternino, and Bruno Saubaméa
Subjects: Blood-brain barrier, Fasting, MCT1, PPAR δ, Endothelial cells, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background The blood-brain barrier (BBB) is pivotal for the maintenance of brain homeostasis and it strictly regulates the cerebral transport of a wide range of endogenous compounds and drugs. While fasting is increasingly recognized as a potential therapeutic intervention in neurology and psychiatry, its impact upon the BBB has not been studied. This study was designed to assess the global impact of fasting upon the repertoire of BBB transporters. Methods We used a combination of in vivo and in vitro experiments to assess the response of the brain endothelium in male rats that were fed ad libitum or fasted for one to three days. Brain endothelial cells were acutely purified and transcriptionaly profiled using RNA-Seq. Isolated brain microvessels were used to assess the protein expression of selected BBB transporters through western blot. The molecular mechanisms involved in the adaptation to fasting were investigated in primary cultured rat brain endothelial cells. MCT1 activity was probed by in situ brain perfusion. Results Fasting did not change the expression of the main drug efflux ATP-binding cassette transporters or P-glycoprotein activity at the BBB but modulated a restrictive set of solute carrier transporters. These included the ketone bodies transporter MCT1, which is pivotal for the brain adaptation to fasting. Our findings in vivo suggested that PPAR δ, a major lipid sensor, was selectively activated in brain endothelial cells in response to fasting. This was confirmed in vitro where pharmacological agonists and free fatty acids selectively activated PPAR δ, resulting in the upregulation of MCT1 expression. Moreover, dosing rats with a specific PPAR δ antagonist blocked the upregulation of MCT1 expression and activity induced by fasting. Conclusions Altogether, our study shows that fasting affects a selected set of BBB transporters which does not include the main drug efflux transporters. Moreover, we describe a previously unknown selective adaptive response of the brain vasculature to fasting which involves PPAR δ and is responsible for the up-regulation of MCT1 expression and activity. Our study opens new perspectives for the metabolic manipulation of the BBB in the healthy or diseased brain.
Published: 2024
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2. Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1

Author: Luana Spano, Cynthia Marie-Claire, Ophélia Godin, Apolline Lebras, Cindie Courtin, Jean-Louis Laplanche, Marion Leboyer, Bruno Aouizerate, Antoine Lefrere, Raoul Belzeaux, Philippe Courtet, Emilie Olié, Caroline Dubertret, Raymund Schwan, Valérie Aubin, Paul Roux, Mircea Polosan, Ludovic Samalin, Emmanuel Haffen, Fondamental Advanced Centers Of Expertise In Bipolar Disorders (Face-Bd) Collaborators, Frank Bellivier, and Bruno Etain
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.
Published: 2024
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3. Genome wide association study of clinical duration and age at onset of sporadic CJD.

Author: Holger Hummerich, Helen Speedy, Tracy Campbell, Lee Darwent, Elizabeth Hill, Steven Collins, Christiane Stehmann, Gabor G Kovacs, Michael D Geschwind, Karl Frontzek, Herbert Budka, Ellen Gelpi, Adriano Aguzzi, Sven J van der Lee, Cornelia M van Duijn, Pawel P Liberski, Miguel Calero, Pascual Sanchez-Juan, Elodie Bouaziz-Amar, Jean-Louis Laplanche, Stéphane Haïk, Jean-Phillipe Brandel, Angela Mammana, Sabina Capellari, Anna Poleggi, Anna Ladogana, Maurizio Pocchiari, Saima Zafar, Stephanie Booth, Gerard H Jansen, Aušrinė Areškevičiūtė, Eva Løbner Lund, Katie Glisic, Piero Parchi, Peter Hermann, Inga Zerr, Brian S Appleby, Jiri Safar, Pierluigi Gambetti, John Collinge, and Simon Mead
Subjects: Medicine, Science
Abstract: Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration and age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research and therapeutics. We assembled and array genotyped sCJD cases diagnosed in life or at autopsy. Clinical duration (median:4, interquartile range (IQR):2.5-9 (months)) was available in 3,773 and age at onset (median:67, IQR:61-73 (years)) in 3,767 cases. Phenotypes were successfully transformed to approximate normal distributions allowing genome-wide analysis without statistical inflation. 53 SNPs achieved genome-wide significance for the clinical duration phenotype; all of which were located at chromosome 20 (top SNP rs1799990, pvalue = 3.45x10-36, beta = 0.34 for an additive model; rs1799990, pvalue = 9.92x10-67, beta = 0.84 for a heterozygous model). Fine mapping, conditional and expression analysis suggests that the well-known non-synonymous variant at codon 129 is the obvious outstanding genome-wide determinant of clinical duration. Pathway analysis and suggestive loci are described. No genome-wide significant SNP determinants of age at onset were found, but the HS6ST3 gene was significant (pvalue = 1.93 x 10-6) in a gene-based test. We found no evidence of genome-wide genetic correlation between case-control (disease risk factors) and case-only (determinants of phenotypes) studies. Relative to other common genetic variants, PRNP codon 129 is by far the outstanding modifier of CJD survival suggesting only modest or rare variant effects at other genetic loci.
Published: 2024
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4. Clustering suicidal phenotypes and genetic associations with brain-derived neurotrophic factor in patients with substance use disorders

Author: Romain Icick, Vanessa Bloch, Nathalie Prince, Emily Karsinti, Jean-Pierre Lépine, Jean-Louis Laplanche, Stéphane Mouly, Cynthia Marie-Claire, Georges Brousse, Frank Bellivier, and Florence Vorspan
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Suicide attempts (SA), especially recurrent SA or serious SA, are common in substance use disorders (SUD). However, the genetic component of SA in SUD samples remains unclear. Brain-derived neurotrophic factor (BDNF) alleles and levels have been repeatedly involved in stress-related psychopathology. This investigation uses a within-cases study of BDNF and associated factors in three suicidal phenotypes (‘any’, ‘recurrent’, and ‘serious’) of outpatients seeking treatment for opiate and/or cocaine use disorder. Phenotypic characterization was ascertained using a semi-structured interview. After thorough quality control, 98 SNPs of BDNF and associated factors (the BDNF pathway) were extracted from whole-genome data, leaving 411 patients of Caucasian ancestry, who had reliable data regarding their SA history. Binary and multinomial regression with the three suicidal phenotypes were further performed to adjust for possible confounders, along with hierarchical clustering and compared to controls (N = 2504). Bayesian analyses were conducted to detect pleiotropy across the suicidal phenotypes. Among 154 (37%) ever suicide attempters, 104 (68%) reported at least one serious SA and 96 (57%) two SA or more. The median number of non-tobacco SUDs was three. The BDNF gene remained associated with lifetime SA in SNP-based (rs7934165, rs10835210) and gene-based tests within the clinical sample. rs10835210 clustered with serious SA. Bayesian analysis identified genetic correlation between ‘any’ and ‘serious’ SA regarding rs7934165. Despite limitations, ‘serious’ SA was shown to share both clinical and genetic risk factors of SA—not otherwise specified, suggesting a shared BDNF-related pathophysiology of SA in this population with multiple SUDs.
Published: 2021
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5. Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Author: Sylvain Lehmann, Julien Dumurgier, Xavier Ayrignac, Cecilia Marelli, Daniel Alcolea, Juan Fortea Ormaechea, Eric Thouvenot, Constance Delaby, Christophe Hirtz, Jérôme Vialaret, Nelly Ginestet, Elodie Bouaziz-Amar, Jean-Louis Laplanche, Pierre Labauge, Claire Paquet, Alberto Lleo, Audrey Gabelle, and for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Subjects: Alzheimer’s disease, Amyloid peptides, Tau proteins, Biomarkers, Cerebrospinal fluid (CSF), Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Amyloid pathology, which is one of the characteristics of Alzheimer’s disease (AD), results from altered metabolism of the beta-amyloid (Aβ) peptide in terms of synthesis, clearance, or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ1–42 is evident in AD, and the CSF ratio Aβ42/Aβ40 has recently been identified as one of the most reliable diagnostic biomarkers of amyloid pathology. Variations in inter-individual levels of Aβ1–40 in the CSF have been observed in the past, but their origins remain unclear. In addition, the variation of Aβ40 in the context of AD studied in several studies has yielded conflicting results. Methods Here, we analyzed the levels of Aβ1–40 using multicenter data obtained on 2466 samples from six different cohorts in which CSF was collected under standardized protocols, centrifugation, and storage conditions. Tau and p-tau (181) concentrations were measured using commercially available in vitro diagnostic immunoassays. Concentrations of CSF Aβ1–42 and Aβ1–40 were measured by ELISA, xMAP technology, chemiluminescence immunoassay (CLIA), and mass spectrometry. Statistical analyses were calculated for parametric and non-parametric comparisons, linear regression, correlation, and odds ratios. The statistical tests were adjusted for the effects of covariates (age, in particular). Results Regardless of the analysis method used and the cohorts, a slight but significant age-independent increase in the levels of Aβ40 in CSF was observed in AD. We also found a strong positive correlation between the levels of Aβ1–40 and p-tau (181) in CSF, particularly in control patients. Conclusions These results indicate that an increase in the baseline level of amyloid peptides, which are associated with an increase in p-tau (181), may be a biological characteristic and possibly a risk factor for AD. Further studies will be needed to establish a causal link between increased baseline levels of Aβ40 and the development of the disease.
Published: 2020
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6. Risk and Protective Factors of Lifetime Cocaine-Associated Chest Pain

Author: Virgile Clergue-Duval, Louise Nicolas-Sacy, Emily Karsinti, El-Hadi Zerdazi, Jean-Louis Laplanche, Georges Brousse, Andries T. Marees, Eske M. Derks, Patrick Henry, Frank Bellivier, Florence Vorspan, and Vanessa Bloch
Subjects: cocaine, chest pain, acute coronary syndrome, opioid maintenance treatment, single nucleotide polymorphism, GUCY1A3, Psychiatry, RC435-571
Abstract: Introduction: Cocaine users often present with repetitive events of cocaine-associated chest pain (CACP), clinically resembling acute coronary syndromes. The aim of the study is to describe the specific risk factors for CACP.Method: Cocaine users (n = 316) were recruited for a multicenter cross-sectional study. Lifetime CACP history, sociodemographic factors, and lifetime use of cocaine and other substances were assessed. Thirty single nucleotide polymorphisms (SNPs) of NOS3, ROCK2, EDN1, GUCY1A3, and ALDH2 genes, suggested by the literature on coronary spasms, were selected. The associations with CACP history were tested using the chi-square test, Student's t-test and logistic regression.Results: Among the 316 subjects [78.5% men, mean age 37.5 years, (standard-deviation ±8.7)], 190 (60.1%) were daily cocaine users and 103 (32.6%) reported a lifetime CACP history. Among those with a lifetime CACP history, the median was 10 events per individual. In multivariate analysis, lifetime CACP history was associated with daily cocaine use [odds-ratio (OR) 3.24; 95% confidence intervals (1.29–9.33)], rapid route of cocaine use [OR 2.33 (1.20–4.64) vs. intranasal use], and lifetime amphetamine use [daily amphetamine use: OR 2.80 (1.25–6.32) and non-daily amphetamine use: OR 2.14 (1.15–4.04) vs. never used]. Patients with lifetime opioid maintenance treatment (OMT) reported significantly less lifetime CACP history [OR 0.35 (0.16–0.76)]. None of the selected SNPs was associated with CACP history after multiple testing corrections.Conclusions: Clinical variables describing the intensity of stimulant use were positively associated with lifetime CACP history, while OMT was negatively associated with it. Specific harm reduction strategies can target these risk factors.
Published: 2021
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7. CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

Author: Adla Boumenir, Emmanuel Cognat, Severine Sabia, Claire Hourregue, Matthieu Lilamand, Aline Dugravot, Elodie Bouaziz-Amar, Jean-Louis Laplanche, Jacques Hugon, Archana Singh-Manoux, Claire Paquet, and Julien Dumurgier
Subjects: Alzheimer’s disease, CSF biomarkers, β-amyloid peptide, Mortality, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Objective Alzheimer’s disease (AD) is the sixth leading cause of death, with an average survival estimated between 5 and 10 years after diagnosis. Despite recent advances in diagnostic criteria of AD, few studies have used biomarker-based diagnostics to determine the prognostic factors of AD. We investigate predictors of death and institutionalization in a population of AD patients with high probability of AD physiopathology process assessed by positivity of three CSF biomarkers. Methods Three hundred twenty-one AD patients with abnormal values for CSF beta-amyloid peptide (Aβ42), tau, and phosphorylated tau levels were recruited from a memory clinic-based registry between 2008 and 2017 (Lariboisiere hospital, Paris, France) and followed during a median period of 3.9 years. We used multivariable Cox models to estimate the hazard ratio (HR) of death and institutionalization for baseline clinical data, genotype of the apolipoprotein E (APOE), and levels of CSF biomarkers. Results A total of 71 (22%) patients were institutionalized and 57 (18%) died during the follow-up. Greater age, male sex, lower MMSE score, and lower CSF Aβ42 level were associated with an increased risk of mortality. One standard deviation lower CSF Aβ42 (135 pg/mL) was associated with a 89% increased risk of death (95% CI = 1.25–2.86; p = 0.002). This association was not modified by age, sex, education, APOE ε4, and disease severity. There was no evidence of an association of tau CSF biomarkers with mortality. None of the CSF biomarkers were associated with institutionalization. Conclusions Lower CSF Aβ42 is a strong prognostic marker of mortality in AD patients, independently of age or severity of the disease. Whether drugs targeting beta-amyloid peptide could have an effect on mortality of AD patients should be investigated in future clinical trials.
Published: 2019
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8. A novel deep intronic variant in ATP7B in five unrelated families affected by Wilson disease

Author: France Woimant, Aurelia Poujois, Adrien Bloch, Tabaras Jordi, Jean‐Louis Laplanche, Hélène Morel, and Corinne Collet
Subjects: ATP7B, deep intronic variant, splicing, Wilson disease, Genetics, QH426-470
Abstract: Abstract Background Wilson disease is an autosomal recessive metabolic disorder resulting from accumulation of excess copper especially in the liver and brain. This disease is mainly characterized by hepatic disorders and less frequently by neuro‐psychiatric disturbances. This recessive disease is due to mutation in ATP7B, which codes for an ATPase involved in copper‐transport across the plasma membrane. Molecular diagnosis of WD is positive in approximately 98% of cases. Also, in few cases, WD patients present a single deleterious mutation (heterozygous) or no mutation after sanger and NGS standard sequencing analysis of ATP7B. Therefore, in these problematic WD cases, we hypothesized that deleterious mutations reside in intronic regions of ATP7B. Methods Complete ATP7B gene was sequenced by Next Generation Sequencing including its promoter. Results Five unrelated families with Wilson disease shared the same novel, deep intronic NG_008806.1 (ATP7B_v001):c.2866‐1521G>A variant in ATP7B. Analysis of RNA transcripts from primary fibroblasts of one patient confirmed the deleterious impact of the intronic variant on splicing and its likely pathologic effect in this compound heterozygote. Conclusion This discovery of a novel intronic mutation in ATP7B has improved the molecular diagnosis of WD in the French patient cohort to greater than 98%. Thus, we recommend complete sequencing of ATP7B gene, including introns, as a molecular diagnostic approach in cases of clinically confirmed WD which lack pathogenic exon or promoter variants in one or both alleles.
Published: 2020
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9. Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study.

Author: Hana Saddiki, Aurore Fayosse, Emmanuel Cognat, Séverine Sabia, Sebastiaan Engelborghs, David Wallon, Panagiotis Alexopoulos, Kaj Blennow, Henrik Zetterberg, Lucilla Parnetti, Inga Zerr, Peter Hermann, Audrey Gabelle, Mercè Boada, Adelina Orellana, Itziar de Rojas, Matthieu Lilamand, Maria Bjerke, Christine Van Broeckhoven, Lucia Farotti, Nicola Salvadori, Janine Diehl-Schmid, Timo Grimmer, Claire Hourregue, Aline Dugravot, Gaël Nicolas, Jean-Louis Laplanche, Sylvain Lehmann, Elodie Bouaziz-Amar, Alzheimer’s Disease Neuroimaging Initiative, Jacques Hugon, Christophe Tzourio, Archana Singh-Manoux, Claire Paquet, and Julien Dumurgier
Subjects: Medicine
Abstract: BackgroundThe ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD.Methods and findingsThis case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1-5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4-31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD.ConclusionsIn this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.
Published: 2020
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10. High genetic carrier frequency of Wilson’s disease in France: discrepancies with clinical prevalence

Author: Corinne Collet, Jean-Louis Laplanche, Justine Page, Hélène Morel, France Woimant, and Aurélia Poujois
Subjects: Wilson’s disease, ATP7B, Clinical prevalence, Heterozygous carrier frequency, Epidemiology, Copper, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Wilson’s disease (WD) is a rare autosomal recessive metabolic disease caused by ATP7B gene mutations tat cause excessively high copper levels, particularly in the liver and brain. The WD phenotype varies in terms of its clinical presentation and intensity. Diagnosing this metabolic disorder is important as a lifelong treatment, based on the use of copper chelating agents or zinc salts, is more effective if it’s started early. Worldwide prevalence of WD is variable, with an average of 1/30,000. In France, a recent study based on French health insurance data estimated the clinical prevalence of the disease to be around 3/200,000. Methods To estimate the genetic prevalence of WD in France, we analysed the ATP7B gene by Next Generation Sequencing from a large French cohort of indiscriminate subjects. Results We observed a high heterozygous carrier frequency of ATP7B in France. Among the 697 subjects studied, 18 variants classified as pathogenic or probably pathogenic were found at heterozygous level in 22 subjects (22 alleles/1394 alleles), yielding a prevalence of 0.032 or 1/31 subjects. Conclusions This considerable and unexplained discrepancy between the heterozygous carrier frequency and the clinical prevalence of WD may be explained by the clinical variability, the incomplete penetrance and the existence of modifiers genes. It suggests that the molecular analysis of ATP7B should be interpreted with caution, always alongside copper assays (ceruloplasmin, relative exchangeable copper, 24 h-urinary copper excretion) with particular respect to exome sequencing.
Published: 2018
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11. Ascorbic Acid Deficiency Prevalence and Associated Cognitive Impairment in Alcohol Detoxification Inpatients: A Pilot Study

Author: Virgile Clergue-Duval, Julien Azuar, Julien Fonsart, Clément Delage, Dorian Rollet, Jihed Amami, Alexia Frapsauce, Marie-Astrid Gautron, Eric Hispard, Frank Bellivier, Vanessa Bloch, Jean-Louis Laplanche, Frank Questel, and Florence Vorspan
Subjects: ascorbic acid, cognitive impairment, alcohol use disorder, malnutrition, central nervous system, sedative use disorder, Therapeutics. Pharmacology, RM1-950
Abstract: Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (p = 0.037) and sedative use disorder (β = −2.77, p = 0.046) were associated with the MoCA score. AAD and AAI are frequent in inpatients admitted for alcohol detoxification. A low level of AA was associated with cognitive impairment in the early period of abstinence.
Published: 2021
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12. Biomarker profiles of Alzheimer's disease and dynamic of the association between cerebrospinal fluid levels of β-amyloid peptide and tau.

Author: Aysha S Mohamed Lafirdeen, Emmanuel Cognat, Severine Sabia, Claire Hourregue, Matthieu Lilamand, Aline Dugravot, Elodie Bouaziz-Amar, Jean-Louis Laplanche, Jacques Hugon, Archana Singh-Manoux, Claire Paquet, and Julien Dumurgier
Subjects: Medicine, Science
Abstract: ObjectiveTo investigate the relationship between cerebrospinal fluid (CSF) β-amyloid peptide (Aβ42) and CSF Tau in a large population of patients referred to memory clinics for investigation of cognitive dysfunction.MethodsWe analyzed Alzheimer's disease (AD) biomarkers in CSF taken from 3565 patients referred to 18 French memory clinics. Patients were classified into four profiles according to levels of CSF biomarkers (A: amyloidosis, N: neurodegeneration). The association between CSF Tau and CSF Aβ42 were analyzed using general linear regression models, in the overall population and stratified by biomarkers profiles. We compared linear and quadratic models using Akaike information criterion. We also assessed change in biomarker profiles in a subset of patients who had 2 assessments of biomarkers.ResultsCSF Tau was negatively associated with CSF Aβ42 in the overall population, following a non-linear quadratic model. However, the nature of this association was different in the 4 profiles: positive association in A-N- profile, negative association in A-N+ and A+N+ profiles, lack of association in A+N- patients. When considering patients with longitudinal data on profiles, 36% of those initially classified as A-N+ evolved to an A+N+ profile.ConclusionsThe nature of the association between CSF Aβ42 and CFS Tau depends on the A/N profiles of patients. These results suggest an increase in CSF Aβ42 early in the disease before its decline while tau pathology progresses, this pattern is particularly observed in non-APOE4 subjects. This phenomenon may explain why some patients with neurodegeneration only markers convert to an AD profile (A+N+) over time.
Published: 2019
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13. Acute Poisoning with Rhabdomyolysis in the Intensive Care Unit: Risk Factors for Acute Kidney Injury and Renal Replacement Therapy Requirement

Author: Pierre-François Rogliano, Sebastian Voicu, Laurence Labat, Nicolas Deye, Isabelle Malissin, Jean-Louis Laplanche, Dominique Vodovar, and Bruno Mégarbane
Subjects: acute kidney injury, poisoning, predictive factor, renal replacement therapy, rhabdomyolysis, Chemical technology, TP1-1185
Abstract: Acute kidney injury (AKI) is the major complication of rhabdomyolysis. We aimed to identify the predictive factors for AKI and renal replacement therapy (RRT) requirement in poisoning-associated rhabdomyolysis. We conducted a cohort study including 273 successive poisoned patients (median age, 41 years) who developed rhabdomyolysis defined as creatine kinase (CK) >1000 IU/L. Factors associated with AKI and RRT requirement were identified using multivariate analyses. Poisonings mainly involved psychotropic drugs. AKI occurred in 88 patients (37%) including 43 patients (49%) who required RRT. Peak serum creatinine and CK were weakly correlated (R2 = 0.17, p < 0.001). Death (13%) was more frequent after AKI onset (32% vs. 2%, p < 0.001). On admission, lithium overdose (OR, 44.4 (5.3–371.5)), serum calcium ≤2.1 mmol/L (OR, 14.3 (2.04–112.4)), female gender (OR, 5.5 (1.8–16.9)), serum phosphate ≥1.5 mmol/L (OR, 2.0 (1.0–4.2)), lactate ≥ 3.3 mmol/L (OR, 1.2 (1.1–1.4)), serum creatinine ≥ 125 µmol/L (OR, 1.05 (1.03–1.06)) and age (OR, 1.04 (1.01–1.07)) independently predicted AKI onset. Calcium-channel blocker overdose (OR, 14.2 (3.8–53.6)), serum phosphate ≥ 2.3 mmol/L (OR, 1.6 (1.1–2.6)), Glasgow score ≤ 5 (OR, 1.12; (1.02–1.25)), prothrombin index ≤ 71% (OR, 1.03; (1.01–1.05)) and serum creatinine ≥ 125 µmol/L (OR, 1.01; (1.00–1.01)) independently predicted RRT requirement. We identified the predictive factors for AKI and RRT requirement on admission to improve management in poisoned patients presenting rhabdomyolysis.
Published: 2020
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14. Exacerbated CSF abnormalities in younger patients with Alzheimer's disease

Author: Julien Dumurgier, Audrey Gabelle, Olivier Vercruysse, Stéphanie Bombois, Jean-Louis Laplanche, Katell Peoc'h, Susanna Schraen, Bernard Sablonnière, Florence Pasquier, Jacques Touchon, Sylvain Lehmann, Jacques Hugon, and Claire Paquet
Subjects: Alzheimer's disease, CSF biomarkers, Age factor, Epidemiology, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Increasing age is the most important risk factor for developing Alzheimer's disease (AD). The aim of this study was to investigate the relationships between age and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ 1–42), total Tau and phosphorylated Tau (pTau-181), in AD and non-AD patients explored for cognitive disorders. 966 patients (AD, n=528; non-AD, n=438) were included between January 2008 and December 2010 (mean age, 69.5 years; mean MMSE, 20.2) from three French memory centers. Multivariable linear regression models were used to study the relationship between CSF biomarker levels and age in AD and non-AD patients. The capacity of each CSF biomarker in discriminating patients was evaluated using the area under the receiver-operating characteristic (ROC) curves by quartile of distribution of age. In AD patients, older age was associated with higher CSF Aβ 1–42 and lower Tau levels. Conversely, in non-AD patients, age was associated with lower CSF Aβ 1–42, higher Tau, and higher pTau-181 levels. In sex-stratified analysis, these relationships were significant only in women. Using ROC curve analysis, CSF AD biomarkers were more discriminant in younger patients than in older ones. In this clinically-based study, younger patients with AD had exacerbated CSF anomalies compared to older patients with AD. CSF biomarkers were more discriminant in younger patients than in older ones for the diagnosis of AD, especially in women. These results support the idea of an overlap in AD neuropathological lesions in oldest subjects with or without AD.
Published: 2013
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15. Inverse association between CSF Aβ 42 levels and years of education in mild form of Alzheimer's disease: The cognitive reserve theory

Author: Julien Dumurgier, Claire Paquet, Sarah Benisty, Claire Kiffel, Claude Lidy, François Mouton-Liger, Hugues Chabriat, Jean-Louis Laplanche, and Jacques Hugon
Subjects: Alzheimer's disease, CSF, Biomarkers, Cognitive reserve, Amyloid β peptide, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: In Alzheimer's disease (AD), the cognitive reserve theory predicts that at any level of assessed clinical severity, the underlying brain pathology is more advanced in patients with more cognitive reserve. Recent evidences suggest that cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We investigated the relationship between education level and CSF concentrations of β-amyloid, total tau and phosphorylated tau (ptau-181) in a cohort of 70 subjects newly diagnosed with AD. We report that CSF concentration of β-amyloid was inversely associated with years of education, after adjustment for age, sex, and severity of the disease. We further demonstrate in stratified analysis that this relation was mainly present in mild form of the disease (CDR1), and was attenuated in more advanced forms of the disease. These results are consistent with the cognitive reserve theory, and suggest that cognitive reserve may be protective against amyloid related cognitive impairment at the onset of the clinical dementia.
Published: 2010
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16. Cerebrospinal fluid PKR level predicts cognitive decline in Alzheimer's disease.

Author: Julien Dumurgier, Francois Mouton-Liger, Pauline Lapalus, Magali Prevot, Jean-Louis Laplanche, Jacques Hugon, Claire Paquet, and Groupe d’Investigation du Liquide Cephalorachidien (GIL) Study Network
Subjects: Medicine, Science
Abstract: The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer's disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of Aβ peptide (Aβ 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE] = 0.03). A lower MMSE at baseline was associated with lower levels of CSF Aβ 1-42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.
Published: 2013
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17. Glycoform-selective prion formation in sporadic and familial forms of prion disease.

Author: Xiangzhu Xiao, Jue Yuan, Stéphane Haïk, Ignazio Cali, Yian Zhan, Mohammed Moudjou, Baiya Li, Jean-Louis Laplanche, Hubert Laude, Jan Langeveld, Pierluigi Gambetti, Tetsuyuki Kitamoto, Qingzhong Kong, Jean-Philippe Brandel, Brian A Cobb, Robert B Petersen, and Wen-Quan Zou
Subjects: Medicine, Science
Abstract: The four glycoforms of the cellular prion protein (PrP(C)) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrP(Sc)) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrP(Sc) in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJD(V180I)) or from Thr to Ala at residue 183 (fCJD(T183A)). Here we report that fCJD(V180I), but not fCJD(T183A), exhibits a proteinase K (PK)-resistant PrP (PrP(res)) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrP(res) species in both fCJD(V180I) and VPSPr is likewise attributable to the absence of PrP(res) glycosylated at the first N-linked glycosylation site at residue 181, as in fCJD(T183A). In contrast to fCJD(T183A), both VPSPr and fCJD(V180I) exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrP(V180I) with a typical glycoform profile from cultured cells generates detectable PrP(res) that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJD(V180I) share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrP(C) to PrP(Sc) is inhibited, probably by a dominant-negative effect, or by other co-factors.
Published: 2013
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18. Correction: Glycoform-Selective Prion Formation in Sporadic and Familial Forms of Prion Disease.

Author: Xiangzhu Xiao, Jue Yuan, Stéphane Haïk, Ignazio Cali, Yian Zhan, Mohammed Moudjou, Baiya Li, Jean-Louis Laplanche, Hubert Laude, Jan Langeveld, Pierluigi Gambetti, Tetsuyuki Kitamoto, Qingzhong Kong, Jean-Philippe Brandel, Brian A. Cobb, Robert B. Petersen, and Wen-Quan Zou
Subjects: Medicine, Science
Published: 2013
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19. Determination of sets of covariating gene expression using graph analysis on pairwise expression ratios.

Author: Emmanuel Curis, Cindie Courtin, Pierre Alexis Geoffroy, Jean-Louis Laplanche, Bruno Saubaméa, and Cynthia Marie-Claire
Published: 2019
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20. The role of environmental factors on sporadic Creutzfeldt-Jakob disease mortality: evidence from an age-period-cohort analysis

Author: Angéline Denouel, Jean-Philippe Brandel, Danielle Seilhean, Jean-Louis Laplanche, Alexis Elbaz, and Stéphane Haik
Subjects: Epidemiology
Abstract: Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of prion diseases. The causes of sCJD are still unknown and exogenous factors may play a role. Worldwide, the number of patients with sCJD has progressively increased over time. This increase can be partly explained by increasing life expectancy and better case ascertainment, but a true increase in the number of sCJD cases cannot be excluded. We estimated mortality rates from sCJD in France (1992–2016) and studied variation in mortality rates by age, period, and time.We included all cases aged 45–89 years old who died with a probable/definite sCJD diagnosis based on the French national surveillance network. We used age-period-cohort (APC) Poisson regression models to study variation in mortality rates by sex, age, period, and time.A total of 2475 sCJD cases aged 45–89 years were included. Mortality rates increased with age, reached a peak between 75 and 79 years, and decreased thereafter. Mortality rates were higher in women than men at younger ages and lower at older ages. The full APC model with a sex×age interaction provided the best fit to the data, thus in favour of sex, age, period, and cohort effects on mortality rates. In particular, mortality rates increased progressively with successive birth cohorts.Based on 25 years of active surveillance in France, we show evidence for sex, age, period, and cohort effects on sCJD mortality. The identification of cohort effects suggests that environmental exposures may play a role in sCJD etiology.
Published: 2023
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21. Circulating IL-6 but not neutrophil extracellular traps levels can predict anakinra effectiveness in patients with severe COVID-19

Author: Vanessa, Granger, Audrey, Fels, Thomas, Huet, Jean-Louis, Laplanche, Sophie, Laplanche, Gilles, Chatellier, Hélène, Beaussier, Sylvie, Chollet-Martin, Luc, de Chaisemartin, and Gilles, Hayem
Subjects: Interleukin 1 Receptor Antagonist Protein, Interleukin-6, Neutrophils, Immunology, Humans, Immunology and Allergy, Cell Biology, Extracellular Traps, COVID-19 Drug Treatment
Abstract: Added data on circulating IL-6 levels can predict COVID-19 severity and IL1RA efficiency.
Published: 2022
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22. Telomere length and mitochondrial DNA copy number in bipolar disorder: A sibling study

Author: Luana Spano, Bruno Etain, Jean-Louis Laplanche, Marion Leboyer, Sébastien Gard, Frank Bellivier, and Cynthia Marie-Claire
Subjects: Psychiatry and Mental health, Biological Psychiatry
Abstract: An accelerated cellular ageing has been observed in bipolar disorder (BD) using biomarkers such as telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). Several risk factors might drive premature ageing in individuals with BD, including a familial predisposition. This study compared TL and mtDNAcn between individuals with BD and their (un)-affected siblings, and explored factors that may explain proband-sibling differences. Sixty individuals with BD and seventy-four siblings (34 affected with BD or mood disorders and 40 unaffected) were included. Quantitative polymerase chain reaction (qPCR) was used to measure TL and mtDNAcn from peripheral blood genomic DNA. TL and mtDNAcn did not significantly differ between probands and their siblings, whatever these latter were affected or not with mood disorders. However, the correlation plots of TL or mtDNAcn in proband-sibling pairs suggested that some pairs were discordant. The within proband-sibling pairs differences for TL and mtDNAcn were not explained by differences in all tested factors. This study shows that probands with BD and their siblings are concordant for TL and mtDNAcn suggesting that they may share some environmental or genetic determinants of these two biomarkers of cellular ageing.
Published: 2022

23. Individual differences in cocaine-induced conditioned place preference in male rats: Behavioral and transcriptomic evidence

Author: Luisa Alessandra Atehortua Martinez, Emmanuel Curis, Nawel Mekdad, Claire Larrieu, Cindie Courtin, Laurent Jourdren, Corinne Blugeon, Jean-Louis Laplanche, Bruno Megarbane, Cynthia Marie-Claire, Nadia Benturquia, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire de biomathématiques, EA 7537 [Paris] (BioSTM), Université Paris Cité - UFR Pharmacie [Santé] (UPCité UFR Pharmacie), Université Paris Cité (UPCité)-Université Paris Cité (UPCité), Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie de l'Ecole Normale Supérieure (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GenomiqueENS (Genomique ENS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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)-Centre National de la Recherche Scientifique (CNRS), and Marie-Claire, Cynthia
Subjects: Pharmacology, Male, immediate early genes, variability, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Individuality, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, conditioned place preference, Nucleus Accumbens, Extinction, Psychological, Rats, Rats, Sprague-Dawley, Psychiatry and Mental health, transcriptomics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cocaine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, RNA, Pharmacology (medical), Transcriptome
Abstract: Background: Substance use disorder emerges in a small proportion of drug users and has the characteristics of a chronic relapsing pathology. Aims: Our study aimed to demonstrate and characterize the variability in the expression of the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. Methods: A cocaine-CPP paradigm in male Sprague–Dawley rats with an extinction period of 12 days and reinstatement was conducted. A statistical model was developed to distinguish rats expressing or not a cocaine-induced place preference. Results: Two groups of rats were identified: rats that did express rewarding effects (CPP expression (CPPE), score >102 s) and rats that did not (no CPP expression (nCPPE), score between −85 and 59 s). These two groups did not show significant differences in a battery of behavioral tests. To identify differentially expressed genes in the CPPE and nCPPE groups, a whole-transcriptome ribonucleic acid-sequencing analysis was performed in the nucleus accumbens (NAc) 24 h after the CPP test. Four immediate early genes ( Fos, Egr2, Nr4a1, and Zbtb37) were differentially expressed in the NAc of CPPE rats after expression of CPP. Variability in cocaine-induced place preference persisted in the CPPE and nCPPE groups after the extinction and reinstatement phases. Transcriptomic differences observed after reinstatement were distinct from those observed immediately after expression of CPP. Conclusion: These new findings provide insights into the identification of mechanisms underlying interindividual variability in the response to cocaine’s rewarding effects.
Published: 2022
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24. Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal‐associated brain damage: A pilot study

Author: Virgile Clergue‐Duval, Agathe Vrillon, Jérôme Jeanblanc, Frank Questel, Julien Azuar, Grégory Fouquet, François Mouton‐Liger, Dorian Rollet, Eric Hispard, Elodie Bouaziz‐Amar, Vanessa Bloch, Alexandra Dereux, Emmanuel Cognat, Cynthia Marie‐Claire, Jean‐Louis Laplanche, Frank Bellivier, Claire Paquet, Mickael Naassila, and Florence Vorspan
Subjects: Pharmacology, Brain, Medicine (miscellaneous), Pilot Projects, Rats, Substance Withdrawal Syndrome, Cohort Studies, Alcoholism, Psychiatry and Mental health, Neurofilament Proteins, Glial Fibrillary Acidic Protein, Animals, Rats, Wistar, Ubiquitin Thiolesterase, Biomarkers
Abstract: In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10
Published: 2022
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25. Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

Author: Sandrine Lablanche, Florence Galtier, Pierre Leroy, Vincent Dubée, Dominique Bonnefont-Rousselot, Patrick Saulnier, Matthieu Wargny, Manuel Etienne, Patrice Darmon, Anne-Laure Borel, Jean-Louis LAPLANCHE, Olivier Lesieur, Bertrand Cariou, Malak Taher, Lydia GUITTET, Vincent Minville, BRUNO MOURVILLIER, Jean-Pierre QUENOT, Bernard Bonnotte, Lucien Marchand, Team2 Carmen, Veronique Kerlan, Pascal Reynier, Nadia Sabbah, Matthieu PICHELIN, Jean-Charles Aurégan, Guillaume Martin-Blondel, Olivier Bourron, Blandine Rammaert, Pierre-Edouard Fournier, Coralie Amadou, Giulia Chinetti, Jean-Christophe Lagier, Didier Raoult, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Sud Francilien, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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), CH Evry-Corbeil, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de diabétologie [CHU Pitié-Salpétrière], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Pneumonia, Viral, Population, 030209 endocrinology & metabolism, law.invention, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, law, Diabetes mellitus, Internal Medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, education, Pandemics, Case report form, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Glycated Hemoglobin, Advanced and Specialized Nursing, Inpatients, Type 1 diabetes, education.field_of_study, business.industry, e-Letters: Observations, COVID-19, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, Hypertension, Etiology, Female, Observational study, Coronavirus Infections, business
Abstract: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, patients with diabetes were rapidly recognized as a high-risk population for severe disease. Indeed, a high prevalence of diabetes among patients with COVID-19 who required hospitalization has been consistently reported, reaching 33.8% in 5,700 people hospitalized for COVID-19 in the New York City area (1). In addition, diabetes was associated with more than a doubled risk of intensive care unit (ICU) admission and more than a tripled risk of death (2). However, precise data regarding the type of diabetes are scarce. We report here the clinical characteristics and early prognosis of patients with type 1 diabetes (T1D) hospitalized for COVID-19 in the nationwide multicenter observational CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study (3). The aim of the CORONADO study was to describe the phenotypic characteristics and prognosis of patients with diabetes admitted with COVID-19 between 10 March and 10 April 2020 in 68 French hospitals. The protocol (ClinicalTrials.gov reg. no. NCT04324736) obtained all regulatory approvals as recently described (3). Inclusion criteria were 1 ) hospitalization for biologically and/or clinically/radiologically attested COVID-19 and 2 ) personal history of diabetes or newly diagnosed diabetes on admission. The composite primary end point combined tracheal intubation for mechanical ventilation and/or death on day 7 (D7). Secondary outcomes included death, tracheal intubation, and discharge on D7. Classification of diabetes was recorded in the electronic case report form as noted in the medical file by the physician in charge of the patient. In the present subanalysis, patients in whom diabetes was diagnosed on admission were excluded since the etiological diagnosis had not been formally established. All cases noted as T1D were carefully reviewed by local investigators and the steering committee …
Published: 2020
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26. Ascorbic Acid Deficiency Prevalence and Associated Cognitive Impairment in Alcohol Detoxification Inpatients: A Pilot Study

Author: Frank Bellivier, Clément Delage, Marie-Astrid Gautron, Vanessa Bloch, Florence Vorspan, Jihed Amami, Eric Hispard, Julien Azuar, Frank Questel, Julien Fonsart, Virgile Clergue-Duval, Dorian Rollet, Jean-Louis Laplanche, and Alexia Frapsauce
Subjects: medicine.medical_specialty, Physiology, medicine.drug_class, medicine.medical_treatment, media_common.quotation_subject, liver cirrhosis, Clinical Biochemistry, Alcohol use disorder, malnutrition, RM1-950, alcohol use disorder, Biochemistry, Article, Internal medicine, Medicine, Ascorbic Acid Deficiency, ascorbic acid, cognitive impairment, central nervous system, sedative use disorder, homeless persons, HIV, Molecular Biology, media_common, business.industry, Alcohol detoxification, Montreal Cognitive Assessment, Cell Biology, Abstinence, medicine.disease, Ascorbic acid, Malnutrition, Sedative, Therapeutics. Pharmacology, business
Abstract: Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (
Published: 2021

27. Childhood trauma and the severity of past suicide attempts in outpatients with cocaine use disorders

Author: Olivier Cottencin, Frank Bellivier, Georges Brousse, Delphine Moisan, Philippe Coeuru, Jean-Pierre Lépine, Bruno Etain, Romain Icick, Florence Vorspan, Maeva Fortias, Jean-Baptiste Trabut, Vanessa Bloch, Beatriz Belforte, Gaël Dupuy, Emily Karsinti, Jean-Louis Laplanche, Clara Chrétienneau, Anne-Laure Pelissier-Alicot, Philippe Lack, Alice Deschenau, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Clinique, Psychanalyse, Développement (CliPsyD), Université Paris Nanterre (UPN), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centres de soins, d'accompagnement et de prévention en addictologie (CSAPA) Monté Christo [Paris] (CSAPA Monté Christo), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Soin, d'Accompagnement et de Prévention en Addictologie (CSAPA) La Chapelle [Paris] (CSAPA Aurore 75 - site EGO), Association Aurore (Aurore 75), Unité de Traitement Ambulatoire des Maladies Addictives [Hôpital Beaujon AP-HP] (UTAMA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre Hospitalier Universitaire Nord, Groupe Hospitalier Paul Guiraud [Villejuif] (GHPG), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Etienne, Centre de soins, d'accompagnement et de prévention en addictologie [Hôpital de la Croix-Rousse, HCL] (CSAPA Lyon), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), BOHAUD, FRANCOISE, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Male, medicine.medical_specialty, recurrent suicide attempt, Substance-Related Disorders, media_common.quotation_subject, impulsiveness, Medicine (miscellaneous), Suicide, Attempted, Cocaine, Adverse Childhood Experiences, Risk Factors, Outpatients, Medicine, Humans, Risk factor, Psychiatry, resilience, ComputingMilieux_MISCELLANEOUS, media_common, childhood trauma, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, substance use disorder, Addiction, suicide, medicine.disease, Substance abuse, Psychiatry and Mental health, serious suicide attempt, Cross-Sectional Studies, Cocaine use, Female, Psychological resilience, addiction, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method: 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results: 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p = 9 × 10-7). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion: These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.
Published: 2021
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28. Author response for 'Influenza vaccination and prognosis of COVID ‐19 in hospitalized patients with diabetes: Results from the CORONADO study'

Author: null A Diallo, null M Pichelin, null M Wargny, null P Gourdy, null JB Bonnet, null S Hadjadj, null B Cariou, null A Sultan, null F Galtier, null Matthieu Wargny, null Pascale Mahot, null Bertrand Cariou, null Samy Hadjadj, null Matthieu Pichelin, null Anne‐Laure Fournier‐Guilloux, null Nicolas Mauduit, null Edith Bigot‐Corbel, null Anne‐Sophie Boureau, null Laure Dekcer, null Audrey Ernould, null Claire Primot, null Anne Seguin, null Marielle Joliveau, null Sonia Pouvreau, null Chloé FOURNIER, null Jeremy Thureau, null Edith Fonteneau, null Pamela Hublain, null Chu Nantes, null Carole Agasse, null Mathilde DE Kergaradec, null Vincent Minville, null Fanny Vardon‐Bounes, null Guillaume Martin‐Blondel, null Pierre Gourdy, null Blandine Tramunt, null Marie‐Christine Turnin, null Hélène Hanaire, null Jean‐Michel Mansuy, null Didier Fabre, null Marie‐Blanche Arhainx, null Laurent Cazals, null Laure Combes, null Emmanuelle Lami, null Mallory Cianferani, null Bruno Megarbane, null Pierre Leroy, null Jean‐François Gautier, null Tiphaine Vidal‐Trecan, null Jean‐Pierre Riveline, null Jean‐Louis Laplanche, null Stéphane Mouly, null Louis Potier, null Ronan Roussel, null Malak Taher, null Yawa Abouleka, null Fetta Yaker, null Aurelie Carlier, null Anne Boutten, null Marilyne Hallot‐Feron, null Fadila Mourah, null Charles Thivolet, null Emilie Blond, null Muriel Rolland, null Josep Verdecho Mendez, null Marine Alexandre, null Julien Pottecher, null Emilie Richer, null Laurent Meyer, null Florina Luca, null Jean‐Marc Lessinger, null Thibault Bahougne, null Bruno Guerci, null Lisa Ludwig, null Siham Benzirar, null Catherine Malaplate, null Thierry Matton, null Julien Poissy, null Karine Faure, null Pierre Fontaine, null Florence Baudoux, null Anne Vambergue, null Jean David Pekar, null Marc Lambert, null Cécile Yelnik, null Amélie Bruandet, null Laurent Petit, null Didier Neau, null Vincent Rigalleau, null Annie Berard, null Amandine Galioot, null Remy Coudroy, null Arnaud Thille, null René Robert, null France Roblot‐Cazenave, null Blandine Rammaert, null Pierre Jean Saulnier, null Xavier Piguel, null Nesrine Benhenda, null Camille Husson, null Celine Olivier, null Florence Torremocha, null Mathilde Fraty, null Marie Flamen d'assigny, null Aurelie Miot, null Valentin Bossard, null Kada Klouche, null Alain Makinson, null Ariane Sultan, null Jean‐Baptiste Bonnet, null Vincent Foulongne, null Florence Galtier, null Cécile Aubron, null Séverine Ansart, null Véronique Kerlan, null Pascale Quiniou, null Jean‐Luc Carre, null Stéphane Quesnot, null Bruno Laviolle, null Carole Schwebel, null Olivier Epaulard, null Pierre‐Yves Benhamou, null Cécile Betry, null Anne‐Laure Borel, null Sandrine Lablanche, null Dorra Guergour, null Catherine Duclos, null Emmanuel Cosson, null Erwan Guyot, null Aurore Deniau, null Phucthutrang Nguyen, null Yves Reznik, null Michael Joubert, null Stéphane Allouche, null Lydia Guittet, null Steven Grange, null Manuel Etienne, null Gaëtan Prévost, null Valéry Brunel, null Jean‐Christophe Lagier, null Didier Raoult, null Anne Dutour, null Bénédicte Gaborit, null Sandrine Boulllu, null Patrice Darmon, null Adèle Lasbleiz, null Mathieu Cerino, null Fanny Romain, null Marie Houssays, null Jean Pierre Quenot, null Lionel Piroth, null Bruno Vergès, null Laurence Duvillard, null Bernard Bonnotte, null Alain Mercat, null Vincent Dubee, null Ingrid Allix, null Patrice Rodien, null Robin Dhersin, null Maylis Lebeault, null Wojciech Trzepizur, null Jocelyne Loison, null Antoine Brangier, null Pierre Asfar, null Pascal Reynier, null Françoise Larcher, null Françoise Joubaud, null Marie‐Rita Andreu, null Geoffrey Urbanski, null Laurent Hubert, null Cedric Annweiler, null Jean Dellamonica, null Johan Courjon, null Nicolas Chevalier, null Giulia Chinetti, null Magda Chafai, null Bruno Mourvillier, null Firouze Bani‐Sadr, null Sarra Barraud, null Brigitte Delemer, null Philippe Gillery, null Pascale Labedade, null Amélie Chabrol, null Alfred Penfornis, null Catherine Petit, null Coralie Amadou, null Maxime Adler, null Clément Dubost, null Pierre‐Louis Conan, null Lyse Bordier, null Franck Ceppa, null Cyril Garcia, null Mathilde Sollier, null Olivier Dupuy, null Sophie Laplance, null Olivier Billuart, null Marie Joseph Aroulanda, null Frédérique Olivier, null Florence Ayon, null Nathalie Wilhelm, null Loic Epelboin, null Nadia Sabbah, null Aurelie Charpin, null Pierre Squara, null Olivier Belliard, null Claude Dubois, null Michel Marre, null Johann Auchabie, null Roxane Courtois, null Thierry Duriez, null Tiphaine Mergey, null Laura Vallee, null Laetitia Seguin, null Abdallah Al‐Salameh, null Jean‐Philippe Lanoix, null Sandrine Soriot‐Thomas, null Anne‐Marie Bourgeois‐Descouls, null Rachel Desailloud, null Natacha Germain, null Bogdan Galusca, null Gwenaelle Belleton, null Nesrine Marouani, null Delia Palaghiu, null Amira Hammour, null Fernando Berdaguer, null Thimothée Klopfenstein, null Hajer Zayet, null Patrice Winiszewski, null Marie Zanusso, null Pauline Garnier, null Ingrid Julier, null Karim Hamzaoui, null Sophie Marty‐Gres, null Tarik Sadki, null Lucile Cadot, null Jean‐Louis Dubost, null Céline Gonfroy, null Catherine Campinos, null Pascale Martres, null Marie Pierre Coulhon, null Nicolas Allou, null Marwa Bachir, null Stella Hoang, null Candice Kembellec, null Olivia Suply, null Fatima Kharcha, null Anne‐Claire Devouge, null Anna Flaus‐Furmanuk, null Isabelle Madeline, null Vincent Ehinger, null Sophie Bastard, null Loic Raffray, null Frederic Renou, null Aude Bojarski, null Caroline Paul, null Karine Borsu, null Angelique Gorlin, null Servane Bernardo, null Carole Truong Ut, null Stephane Renaud, null Antoine Vignoles, null Emilie Foch, null Laurie Masse, null Hubert Grand, null Helene Ferrand, null Christelle Raffaitin‐Cardin, null Hadjer Zellagui, null Celine Castang‐Brachet, null Frederique Boury, null Ana Alvarez Tena, null Isabelle Moura, null Pierre Kalfon, null Juliana Darasteanu, null Arnaud Monier, null Pascal Foucault, null Alexandra Depuille, null Stéphanie Laugier‐Robiolle, null Patrick Caneiro, null Maud Basso, null Etienne Larger, null Samir Bouam, null Wahiba Benzenati, null Leila Ait Bachir, null Camille Cussac Pillegand, null Marc Vasse, null Christophe Michard, null Nathanaëlle Montanier, null Luc Millot, null Françoise Crepet, null Danielle Ratsimba, null Kevin Bouiller, null Sophie Borot, null Isabelle Bruckert, null Annie Clergeot, null Franck Schillo, null Dorothée Vignes, null Muriel Bourgeon‐Ghittori, null Hamoud Lachgar, null Claire Lambert DE Cursay, null Stéphane Levante, null Jean Charles Auregan, null Antoine Merlet, null Cécile Zaragoza, null Gwénaëlle Arnault, null Anne‐Gaëlle Loupp, null Olivier Lesieur, null Mariam Roncato‐Saberan, null Didier Gouet, null Romain Lemarie, null Hong_an Allano, null Emmanuel Vivier, null Caroline Pariset, null Cédric Luyton, null Lucien Marchand, null Fanny Doroszewski, null Matthieu Pecquet, null Laurent Perard, null Sylvie Vuillermoz‐Blas, null Nicolas Kacki, null Patricia Charrier, null Amélie Ducet‐Boiffard, null Françoise Desroys Roure, null Olivier Bourron, null Dominique Bonnefont‐Rousselot, null Suzanne Laroche, null Franck Phan, null Agnès Hartemann, null Cyrielle Caussy, null Emmanuel Disse, null Claude Guerin, null Thomas Perpoint, null Philippe Moulin, null Régine Cartier, null Geoffroy Hariri, null Dorothée Chopin, null Camille Vatier, null Nathalie Bourcigaux, null Emmanuelle Chaigneau, null Sophie Christin‐Maitre, null Bruno Donadille, null Bruno Feve, null Sophie Lamothe, null Julie Sarfati, null Pascal Pernet, null Anne Chambon, null Delphine Demarsy, null Hugo Campagne, null Françoise Latil‐Plat, null Monica Berne, null Marilyne Grinand, null Marion Touzet, null Aydrey Zabulon, null Jocelyne Craspag, null Catherine Ledoux, null Cedric Contaret, null Blandine Janand‐Delenne, null Anaïs Giraud, null Marie Lou Lacrimini, null Joëlle Arrivie, null Deborah Ancelle, null Carine Guillois, null Bénédicte Fremy, null Amina Chaalal, null Gaëlle Barrande, null Anne Dorange, null Eglantine Rouanet, null Dominique Seret‐Begue, null Audrey Saoud, null Anne‐Marie Guedj, null Nathalie Bedos, null Fritz‐Line Velayoudom, null Marie Dumas, null Benoite Gonda, null Christine Coffin, null Stéphanie Gibiat, null Myriam Lungo, null Chantal Bully, null Pierre Serusclat, null Stella Bully, null Patricia Carre, null Jean‐Philippe Leberre, null Carlos Elkhoury, null Marine Thieux, null Laetitia Paradisi‐Prieur, and null CORONADO investigators
Subjects: Vaccination, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Diabetes mellitus, Medicine, business, medicine.disease
Published: 2021
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29. Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Author: Julien, Dumurgier, Séverine, Sabia, Henrik, Zetterberg, Charlotte, Teunissen, Bernard, Hanseeuw, Adelina, Orellana, Susanna, Schraen, Audrey, Gabelle, Mercè, Boada, Thibaud, Lebouvier, Eline A J, Willemse, Emmanuel, Cognat, Agustin, Ruiz, Claire, Hourregue, Matthieu, Lilamand, Elodie, Bouaziz-Amar, Jean-Louis, Laplanche, Sylvain, Lehmann, Florence, Pasquier, Philip, Scheltens, Kaj, Blennow, Archana, Singh-Manoux, Claire, Paquet, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology
Subjects: Male, Amyloid beta-Peptides, Alzheimer Disease, Positron-Emission Tomography, Humans, Female, tau Proteins, Neurology (clinical), Biomarkers, Peptide Fragments, Aged
Abstract: Background and ObjectivesTo elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.MethodsLow and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients.ResultsA total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%.DiscussionThe proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
Published: 2021
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30. Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors

Author: El-Hadi Zerdazi, Emmanuel Curis, Emily Karsinti, Romain Icick, Maeva Fortias, Philippe Batel, Olivier Cottencin, Cyrille Orizet, Aurélia Gay, Philippe Coeuru, Alice Deschenau, Philippe Lack, Delphine Moisan, Anne-Laure Pelissier-Alicot, Arnaud Plat, Jean-Baptiste Trabut, Isabelle Kousignian, Luana Boumendil, Eric Vicaut, Nathalie Prince, Jean-Louis Laplanche, Frank Bellivier, Jean-Pierre Lépine, Cynthia Marie-Claire, Georges Brousse, Florence Vorspan, and Vanessa Bloch
Subjects: Pharmacology, Psychiatry and Mental health, Cocaine-Related Disorders, Phenotype, Cocaine, Hallucinations, Risk Factors, Humans, Pharmacology (medical), Toxicology
Abstract: Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity.Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately.Cocaine dependence (pOur study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background.
Published: 2021

31. QT length during methadone maintenance treatment: gene × dose interaction

Author: Frank Bellivier, François Naccache, Vanessa Bloch, Jean Pierre Lepine, Florence Vorspan, Stéphane Mouly, Andries T. Marees, Cynthia Marie-Claire, Nathalie Prince, Jean-Louis Laplanche, El Hadi Zerdazi, Variabilité de réponse aux Psychotropes (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), Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Fondation FondaMental [Créteil], Economics, Graduate School, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, University of Amsterdam [Amsterdam] (UvA), QIMR Berghofer Medical Research Institute, and Marie-Claire, Cynthia
Subjects: Male, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, rs11911509, 030226 pharmacology & pharmacy, MESH: Dose-Response Relationship, Drug, methadone, Electrocardiography, 0302 clinical medicine, NOS1AP, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, MESH: Middle Aged, Heroin Dependence, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Long QT Syndrome, Potassium Channels, Voltage-Gated, MESH: Young Adult, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cardiology, cardiovascular system, KCNE1, Female, medicine.drug, Adult, medicine.medical_specialty, Methadone maintenance, congenital, hereditary, and neonatal diseases and abnormalities, Single-nucleotide polymorphism, QT prolongation, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, QT interval, Sudden death, MESH: Opiate Substitution Treatment, Young Adult, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, SDG 3 - Good Health and Well-being, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, MESH: Heroin Dependence, Opiate Substitution Treatment, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Risk factor, Pharmacology, MESH: Humans, Dose-Response Relationship, Drug, MESH: Long QT Syndrome, business.industry, MESH: Adult, MESH: Male, MESH: Electrocardiography, Minor allele frequency, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Methadone, business, MESH: Potassium Channels, Voltage-Gated, MESH: Female, 030217 neurology & neurosurgery, Methadone
Abstract: Methadone is known to be a risk factor for sudden death by enlarging ECG QT corrected (QTc) interval. For other medical conditions, QTc lengthening has been described as the result of interactions between pharmacological treatments and genetic factors. Former heroin-dependent subjects under methadone maintenance treatment in remission for at last 3 months were recruited. We studied the association between QTc length (Bazett formula) and 126 SNPs located on five genes (KCNE1, KCNQ1, KCNH2, NOS1AP and SCN5A) previously associated with drug-induced QT prolongation. Both SNP-based and gene-based approaches were used, and we tested also the interaction of the top SNP with methadone dosage to predict the QTc length. In our sample of 154 patients, current methadone daily dose was associated with QTc length (r Pearson = 0.26; P = 10 −3 ). Only one SNP, rs11911509 on KCNE1, remained significantly associated with QT length after correction for multiple testing (P = 3.84 × 10 −4 ; p corrected = 0.049). Using a gene-based approach, KCNE1 was also significantly associated with QTc length (p empirical = 0.02). We found a significant interaction between methadone dosage and rs11911509 minor allele count (allele A vs. C; P = 0.01). Stratified analysis revealed that the correlation between QTc length and methadone dosage was restricted only to AA carriers of this top SNP. Patients’ genetic background should be taken into account in the case of clinically relevant QT enlargement during methadone maintenance treatment.
Published: 2019
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32. Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat

Author: Mélanie Etheve-Quelquejeu, Stéphanie Chasseigneaux, Clemens Zwergel, Huixiong Chen, Nadia Benturquia, Patrizia Campolongo, Luisa Alessandra Atehortua-Martinez, Jean-Louis Laplanche, Cyriaque Masniere, Jacques Callebert, Antonello Mai, Bruno Mégarbane, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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 Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique (NAVVEC - UM 81 (UMR 8206/ U705)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Pyrrolidines, medicine.drug_class, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Synthetic cathinone, Prefrontal Cortex, Methylenedioxypyrovalerone, Pharmacology, Drug Administration Schedule, Nucleus Accumbens, Designer Drugs, Rats, Sprague-Dawley, MDPV, 03 medical and health sciences, 0302 clinical medicine, Dopamine, medicine, Animals, Pharmacology (medical), Benzodioxoles, Maze Learning, conditioned place preference, dopamine, neurobehavioral effects, ΔFosB, Behavior, Animal, Chemistry, Benzazepines, Synthetic Cathinone, Conditioned place preference, Rats, 030227 psychiatry, Designer drug, Psychiatry and Mental health, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Caudate Nucleus, Locomotion, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability. Aims: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties. Methods: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex. Results: Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex. Conclusions: Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.
Published: 2019
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33. International initiative for harmonization of cerebrospinal fluid diagnostic comments in Alzheimer's disease

Author: Mari L DeMarco, Clementine Gondolf, Léonor Nogueira, Michael Khalil, Koen Poesen, Aurélie Bedel, Andreas Jeromin, Marie-Céline Blanc, Daniel Alcolea, Markus Otto, Agnieszka Kulczyńska-Przybik, Marc Suárez-Calvet, Benoit Rucheton, Muriel Quillard-Muraine, Hermann Esselmann, Maria Bjerke, Alberto Lleó, Anne Fogli, Frédérique Grandhomme, Olivier Bousiges, Federico Verde, M D'Onofrio, Oriol Grau-Rivera, Ashvini Keshavan, Hayrettin Tumani, Melanie Hart, Isabelle Quadrio, Sylvain Lehmann, Albert Puig‐Pijoan, Lucie Vaudran, Marcel M. Verbeek, Lucilla Parnetti, Peter Koertvelyessy, Catherine Malaplate, Armand Perret-Liaudet, Henrik Zetterberg, Jens Wiltfang, Lisa Vermunt, Chinedu T. Udeh-Momoh, Katell Poec, Claire Paquet, Magda Tsolaki, Barbara Mroszko, Jean-Baptiste Oudart, Jean-Louis Laplanche, Sebastiaan Engelborghs, Miles D. Chapman, Elodie Bouaziz Amar, Jonathan Vogelgsang, Susanna Schraen, Edith Bigot-Corbel, Elisabetta Galloni, Adelina Orellana, Constance Delaby, Anne Beaume, Diane Dufour-Rainfray, and Charlotte E. Teunissen
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Harmonization, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cerebrospinal fluid, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Intensive care medicine, business
Published: 2020
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34. An in vivo Caenorhabditis elegans model for therapeutic research in human prion diseases

Author: Jean-Philippe Brandel, Etienne Levavasseur, Stéphane Haïk, Nicolas Bizat, Sofian Laoues, Patrice Beaudry, Valeria Parrales, Julian Roussel, Nicolas Privat, Alexianne Gougerot, Philippe Ravassard, Sébastien Normant, and Jean-Louis Laplanche
Subjects: animal diseases, Transgene, Benzocaine, PrPSc Proteins, Context (language use), Biology, medicine.disease_cause, Protein Aggregation, Pathological, Prion Proteins, Prion Diseases, Animals, Genetically Modified, Piroxicam, Tubulin, Genetic model, medicine, Animals, Humans, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Mutation, Naloxone, Neurodegeneration, Brain, medicine.disease, biology.organism_classification, Phenotype, nervous system diseases, Cell biology, Disease Models, Animal, Neurology (clinical)
Abstract: Human prion diseases are fatal neurodegenerative disorders that include sporadic, infectious and genetic forms. Inherited Creutzfeldt-Jakob disease due to the E200K mutation of the prion protein-coding gene is the most common form of genetic prion disease. The phenotype resembles that of sporadic Creutzfeldt-Jakob disease at both the clinical and pathological levels, with a median disease duration of 4 months. To date, there is no available treatment for delaying the occurrence or slowing the progression of human prion diseases. Existing in vivo models do not allow high-throughput approaches that may facilitate the discovery of compounds targeting pathological assemblies of human prion protein or their effects on neuronal survival. Here, we generated a genetic model in the nematode Caenorhabditis elegans, which is devoid of any homologue of the prion protein, by expressing human prion protein with the E200K mutation in the mechanosensitive neuronal system. Expression of E200K prion protein induced a specific behavioural pattern and neurodegeneration of green fluorescent protein-expressing mechanosensitive neurons, in addition to the formation of intraneuronal inclusions associated with the accumulation of a protease-resistant form of the prion protein. We demonstrated that this experimental system is a powerful tool for investigating the efficacy of anti-prion compounds on both prion-induced neurodegeneration and prion protein misfolding, as well as in the context of human prion protein. Within a library of 320 compounds that have been approved for human use and cross the blood–brain barrier, we identified five molecules that were active against the aggregation of the E200K prion protein and the neurodegeneration it induced in transgenic animals. This model breaks a technological limitation in prion therapeutic research and provides a key tool to study the deleterious effects of misfolded prion protein in a well-described neuronal system.
Published: 2020

35. Acute Poisoning with Rhabdomyolysis in the Intensive Care Unit: Risk Factors for Acute Kidney Injury and Renal Replacement Therapy Requirement

Author: Laurence Labat, Isabelle Malissin, Dominique Vodovar, Nicolas Deye, Pierre-François Rogliano, Jean-Louis Laplanche, Bruno Mégarbane, Sebastian Voicu, Mégarbane, Bruno, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Laboratoire de Toxicologie Biologique, Hôpital Lariboisière, Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Health, Toxicology and Mutagenesis, medicine.medical_treatment, lcsh:Chemical technology, Toxicology, urologic and male genital diseases, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Gastroenterology, Article, law.invention, predictive factor, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Internal medicine, medicine, lcsh:TP1-1185, 030212 general & internal medicine, Renal replacement therapy, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Creatinine, Chemical Health and Safety, biology, business.industry, Acute kidney injury, Glasgow Coma Scale, 030208 emergency & critical care medicine, medicine.disease, Intensive care unit, female genital diseases and pregnancy complications, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, poisoning, chemistry, acute kidney injury, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, biology.protein, rhabdomyolysis, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Creatine kinase, business, Rhabdomyolysis, renal replacement therapy, Cohort study
Abstract: Acute kidney injury (AKI) is the major complication of rhabdomyolysis. We aimed to identify the predictive factors for AKI and renal replacement therapy (RRT) requirement in poisoning-associated rhabdomyolysis. We conducted a cohort study including 273 successive poisoned patients (median age, 41 years) who developed rhabdomyolysis defined as creatine kinase (CK) &gt, 1000 IU/L. Factors associated with AKI and RRT requirement were identified using multivariate analyses. Poisonings mainly involved psychotropic drugs. AKI occurred in 88 patients (37%) including 43 patients (49%) who required RRT. Peak serum creatinine and CK were weakly correlated (R2 = 0.17, p &lt, 0.001). Death (13%) was more frequent after AKI onset (32% vs. 2%, p &lt, 0.001). On admission, lithium overdose (OR, 44.4 (5.3&ndash, 371.5)), serum calcium &le, 2.1 mmol/L (OR, 14.3 (2.04&ndash, 112.4)), female gender (OR, 5.5 (1.8&ndash, 16.9)), serum phosphate &ge, 1.5 mmol/L (OR, 2.0 (1.0&ndash, 4.2)), lactate &ge, 3.3 mmol/L (OR, 1.2 (1.1&ndash, 1.4)), serum creatinine &ge, 125 &micro, mol/L (OR, 1.05 (1.03&ndash, 1.06)) and age (OR, 1.04 (1.01&ndash, 1.07)) independently predicted AKI onset. Calcium-channel blocker overdose (OR, 14.2 (3.8&ndash, 53.6)), serum phosphate &ge, 2.3 mmol/L (OR, 1.6 (1.1&ndash, 2.6)), Glasgow score &le, 5 (OR, 1.12, (1.02&ndash, 1.25)), prothrombin index &le, 71% (OR, 1.03, (1.01&ndash, 1.05)) and serum creatinine &ge, mol/L (OR, 1.01, (1.00&ndash, 1.01)) independently predicted RRT requirement. We identified the predictive factors for AKI and RRT requirement on admission to improve management in poisoned patients presenting rhabdomyolysis.
Published: 2020
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36. Genome-wide association study identifies risk variants for sporadic Creutzfeldt-Jakob disease in STX6 and GAL3ST1

Author: Anna Poleggi, John Collinge, Carla A. Ibrahim-Verbaas, Jean-Philippe Brandel, Emma Jones, Dimitriadis A, Anna Bartoletti-Stella, James Uphill, Christiane Stehmann, Mok Th, Gerard H. Jansen, Tracy Campbell, Zafar S, Holger Hummerich, van Duijn C, Jiri G. Safar, Ewa Golanska, Martinón-Torres F, Aili Golubjatnikov, Michael B. Coulthart, Zane Jaunmuktane, Beata Sikorska, Giuseppe Matullo, Miguel Calero, Jerome Whitfield, Sabina Capellari, Jean-Louis Laplanche, Kathleen Glisic, Gabor G. Kovacs, Richard Knight, Helen Speedy, Juan Ps, Olga Calero, Jean-Charles Lambert, Stéphane Haïk, Anna Ladogana, Akin Nihat, Stephanie A. Booth, Serena Aneli, Herbert Budka, Pawel P. Liberski, Piero Parchi, Shannon Sarros, Jacqueline M. Linehan, Sebastian Brandner, Maurizio Pocchiari, Ahmed P, Michael D. Geschwind, Fronztek K, Antonio Salas, Inga Zerr, Janis Blevins, Elodie Bouaziz-Amar, Brian S. Appleby, Steven J. Collins, P. Gambetti, Hata Karamujić-Čomić, Adriano Aguzzi, Philippe Amouyel, van der Lee S, Penny Norsworthy, Parmjit S. Jat, Liam Quinn, Emmanuelle Viré, and Simon Mead
Subjects: Genetics, 0303 health sciences, biology, animal diseases, Tau protein, STX6, Single-nucleotide polymorphism, Genome-wide association study, medicine.disease, 3. Good health, Progressive supranuclear palsy, PRNP, nervous system diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, biology.protein, Gene, 030217 neurology & neurosurgery, Exome sequencing, 030304 developmental biology
Abstract: Mammalian prions are lethal pathogens composed of fibrillar assemblies of misfolded prion protein. Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the gene that encodes prion protein (PRNP) are strong risk factors for sCJD, but although the condition has heritability similar to other neurodegenerative disorders, no other risk loci have yet been confirmed. By genome-wide association in European ancestry populations, we found three replicated loci (cases n=5208, within PRNP, STX6, and GAL3ST1) and two further unreplicated loci were significant in gene-wide tests (within PDIA4, BMERB1). Exome sequencing in 407 sCJD cases, conditional and transcription analyses suggest that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 and PDIA4 associate with increased expression of the major transcripts in disease-relevant brain regions. Alteration of STX6 expression does not modify prion propagation in a neuroblastoma cell model of mouse prion infection. We went on to analyse the proteins histologically in diseased tissue and examine the effects of risk variants on clinical phenotypes using deep longitudinal clinical cohort data. Risk SNPs in STX6, a protein involved in the intracellular trafficking of proteins and vesicles, are shared with progressive supranuclear palsy, a neurodegenerative disease associated with the misfolded protein tau. We present the first evidence of statistically robust associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism.
Published: 2020
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37. Additional file 1 of Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Author: Lehmann, Sylvain, Dumurgier, Julien, Ayrignac, Xavier, Marelli, Cecilia, Alcolea, Daniel, Ormaechea, Juan Fortea, Thouvenot, Eric, Delaby, Constance, Hirtz, Christophe, Vialaret, Jérôme, Ginestet, Nelly, Bouaziz-Amar, Elodie, Jean-Louis Laplanche, Labauge, Pierre, Paquet, Claire, Lleo, Alberto, and Gabelle, Audrey
Abstract: Additional file 1 : SupTable 1. Number of patients/samples in each clinical group and Aβ40 detection method used.
Published: 2020
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38. Plos Med

Author: Lucia Farotti, Kaj Blennow, Claire Paquet, Inga Zerr, Gaël Nicolas, Alzheimer’s Disease Neuroimaging Initiative, Henrik Zetterberg, Christophe Tzourio, Janine Diehl-Schmid, David Wallon, Audrey Gabelle, Panagiotis Alexopoulos, Julien Dumurgier, Emmanuel Cognat, Hana Saddiki, Christine Van Broeckhoven, Timo Grimmer, Aurore Fayosse, Matthieu Lilamand, Jean-Louis Laplanche, Lucilla Parnetti, Séverine Sabia, Sebastiaan Engelborghs, Elodie Bouaziz-Amar, Aline Dugravot, Adelina Orellana, Sylvain Lehmann, Nicola Salvadori, Mercè Boada, Jacques Hugon, Maria Bjerke, Archana Singh-Manoux, Peter Hermann, Itziar de Rojas, Claire Hourregue, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije Universiteit Brussel (VUB), University of Antwerp (UA), 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), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University of Gothenburg (GU), Sahlgrenska University Hospital [Gothenburg], University College of London [London] (UCL), Università degli Studi di Perugia (UNIPG), University Medical Center Göttingen (UMG), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Universitat Internacional de Catalunya [Barcelona] (UIC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Clinical Biology, Pathologic Biochemistry and Physiology, and Alzheimers Dis Neuroimaging Initia
Subjects: Apolipoprotein E, Male, cerebrospinal fluid [Apolipoprotein E4], Aging, Physiology, Epidemiology, Apolipoprotein E4, genetics [Alzheimer Disease], 030204 cardiovascular system & hematology, Cardiovascular Medicine, Alzheimer's Disease, Nervous System, Biochemistry, Cohort Studies, 0302 clinical medicine, Medical Conditions, Cognition, Learning and Memory, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, genetics [Apolipoprotein E4], apolipoprotein E, Cerebrospinal Fluid, Aged, 80 and over, education.field_of_study, diagnosis [Alzheimer Disease], Neurodegenerative Diseases, General Medicine, Middle Aged, 3. Good health, Body Fluids, cerebrospinal fluid [Alzheimer Disease], cerebrospinal fluid [Biomarkers], Neurology, Cardiovascular Diseases, genetics [Aging], Female, Alzheimer's disease, Anatomy, Cohort study, Research Article, Adult, medicine.medical_specialty, cerebrospinal fluid biomarker, Genotype, case-control study, Lipoproteins, Population, Clinical Neurology, Cardiology, cerebrospinal fluid [Aging], 03 medical and health sciences, Memory, Diagnostic Medicine, Alzheimer Disease, Internal medicine, Mental Health and Psychiatry, Internal Medicine, Dementia, Humans, ddc:610, education, HEALTHY, Aged, business.industry, Case-control study, Biology and Life Sciences, Proteins, Odds ratio, Cardiovascular Disease Risk, medicine.disease, Apolipoproteins, age, Medical Risk Factors, Case-Control Studies, Attributable risk, Cognitive Science, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business, Biomarkers, Neuroscience
Abstract: Background The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level., In a case-control study using cerebrospinal fluid biomarkers, Hana Saddiki and colleagues investigate how age is related to the association between Apolipoprotein E genotype and Alzheimer's disease, among individuals with and without Alzheimer's disease in Europe and the US., Author summary Why was this study done? The ε4 allele of apolipoprotein E (APOE) gene (APOE4) and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The recent development of diagnostic criteria based on biomarkers that reflect brain β-amyloid and tau lesions (β-amyloid deposition, pathologic tau, neurodegeneration [A/T/N] classification]) increases homogeneity in diagnosed cases. The strength of association of AD with risk factors can be better determined using biomarker-based AD compared with AD diagnosis based only on clinical criteria because the latter are known to lack specificity as a result of difficulties in ruling out other causes of dementia. What did the researchers do and find? We compared the overall and age-specific association between APOE4 and AD using a case–control study that included 1,593 AD cases from memory clinics with positive cerebrospinal fluid biomarkers and 11,723 dementia-free controls drawn from two longitudinal cohort studies. The use of a large number of cases and controls allows assessment of whether the association between APOE4 and AD is dependent on age. Compared with controls, patients with AD were more likely to carry one APOE4 (odds ratio [OR] = 4.6) or two APOE4 (OR = 25.3). This association was significantly modified by age, with the strongest association seen between 65 and 70 years of age and weaker associations at the two tails of the age distribution. What do these findings mean? Incorporating biomarkers for diagnosis of AD identified an association with APOE4 that is apparently greater than has been previously reported using clinical diagnosis of the disease. The impact of APOE4 on the risk of AD was strongest between the 65 and 70 years of age, earlier than the mean age at diagnosis in this study, which was 72.8 years.
Published: 2020
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39. Additional file 4 of Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Author: Lehmann, Sylvain, Dumurgier, Julien, Ayrignac, Xavier, Marelli, Cecilia, Alcolea, Daniel, Ormaechea, Juan Fortea, Thouvenot, Eric, Delaby, Constance, Hirtz, Christophe, Vialaret, Jérôme, Ginestet, Nelly, Bouaziz-Amar, Elodie, Jean-Louis Laplanche, Labauge, Pierre, Paquet, Claire, Lleo, Alberto, and Gabelle, Audrey
Abstract: Additional file 4 : Sup-Figure 2. ROC curves of Aβ40, Aβ42 and Aβ42/40 ROC curves of Aβ40, Aβ42 and Aβ42/40 for the detection of AD in different cohorts. AUC of Aβ40 had lower values than the other biomarkers (Mtp-1 0.686 (0.638 to 0.731); Mtp-2 0.751 (0.711 to 0.788); Paris 0,679 (0.641 to 0.716); SPIN-Barcelona 0.730 (0.667 to 0,787)).
Published: 2020
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40. Additional file 5 of Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Author: Lehmann, Sylvain, Dumurgier, Julien, Ayrignac, Xavier, Marelli, Cecilia, Alcolea, Daniel, Ormaechea, Juan Fortea, Thouvenot, Eric, Delaby, Constance, Hirtz, Christophe, Vialaret, Jérôme, Ginestet, Nelly, Bouaziz-Amar, Elodie, Jean-Louis Laplanche, Labauge, Pierre, Paquet, Claire, Lleo, Alberto, and Gabelle, Audrey
Subjects: mental disorders
Abstract: Additional file 5 : Sup-Figure 3. Aβ40 in different clinical groups. The Montpellier, Paris and SPIN-Barcelona cohorts displayed a large range of pathological samples from patients with Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA), frontotemporal degeneration (FTD), mild cognitive impairment (MCI), normal pressure hydrocephalus (NPH), vascular dementia (VASC), other neurological diseases (amytrophic lateral sclerosis, Parkinson’s disease, Lewy Body dementia..) (Other) and control (subjective cognitive impairment). Box plots with median and 25th/75th percentile of CSF Aβ40 values are plotted for the four cohorts (panels A-D). Note that the distribution of the diagnoses differ in the cohorts (see Methods). Non parametric Mann–Whitney U test were performed between the AD and the other clinical groups. P values below statistical significance are in red.
Published: 2020
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41. Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study

Author: Gabor G. Kovacs, Stephanie A. Booth, Sebastian Brandner, Penny Norsworthy, Anna Ladogana, Akin Nihat, Herbert Budka, Saima Zafar, Helen Speedy, Antonio Salas, Parvin Ahmed, Holger Hummerich, Gerard H. Jansen, Tze How Mok, Michael D. Geschwind, Beata Sikorska, Maurizio Pocchiari, Christiane Stehmann, Sabina Capellari, Jean-Louis Laplanche, Sven J. van der Lee, Emma Jones, Jean-Charles Lambert, Olga Calero, Pierluigi Gambetti, Ewa Golanska, Serena Aneli, Richard Knight, Giuseppe Matullo, Pawel P. Liberski, Athanasios Dimitriadis, Jerome Whitfield, Hata Karamujić-Čomić, Federico Martinón-Torres, Emmanuelle Viré, Jiri G. Safar, Tracy Campbell, Pascual Sánchez-Juan, Katie Glisic, Anna Bartoletti-Stella, Carla A. Ibrahim-Verbaas, Adriano Aguzzi, Anna Poleggi, Aili Golubjatnikov, Karl Frontzek, Jean Phillipe Brandel, Phillipe Amouyel, Parmjit S. Jat, Zane Jaunmuktane, Simon Mead, Steven J. Collins, Inga Zerr, Liam Quinn, Piero Parchi, Janis Blevins, Elodie Bouaziz-Amar, Brian S. Appleby, Shannon Sarros, Jacqueline M. Linehan, Miguel Calero, Michael B. Coulthart, Stéphane Haïk, John Collinge, James Uphill, Cornelia M. van Duijn, Diseases, Network Centre for Biomedical Research in Neurodegenerative, Jones E., Hummerich H., Vire E., Uphill J., Dimitriadis A., Speedy H., Campbell T., Norsworthy P., Quinn L., Whitfield J., Linehan J., Jaunmuktane Z., Brandner S., Jat P., Nihat A., How Mok T., Ahmed P., Collins S., Stehmann C., Sarros S., Kovacs G.G., Geschwind M.D., Golubjatnikov A., Frontzek K., Budka H., Aguzzi A., Karamujic-Comic H., van der Lee S.J., Ibrahim-Verbaas C.A., van Duijn C.M., Sikorska B., Golanska E., Liberski P.P., Calero M., Calero O., Sanchez-Juan P., Salas A., Martinon-Torres F., Bouaziz-Amar E., Haik S., Laplanche J.-L., Brandel J.-P., Amouyel P., Lambert J.-C., Parchi P., Bartoletti-Stella A., Capellari S., Poleggi A., Ladogana A., Pocchiari M., Aneli S., Matullo G., Knight R., Zafar S., Zerr I., Booth S., Coulthart M.B., Jansen G.H., Glisic K., Blevins J., Gambetti P., Safar J., Appleby B., Collinge J., Mead S., Universidad de Cantabria, Neurology, Amsterdam Neuroscience - Neurodegeneration, and Epidemiology
Subjects: 0301 basic medicine, epidemiology [Creutzfeldt-Jakob Syndrome], Tau protein, Single-nucleotide polymorphism, Genome-wide association study, diagnosis [Creutzfeldt-Jakob Syndrome], Disease, genetics [Genetic Loci], methods [Genome-Wide Association Study], Polymorphism, Single Nucleotide, Creutzfeldt-Jakob Syndrome, PRNP, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Humans, Genetic Predisposition to Disease, ddc:610, genetics [Genetic Predisposition to Disease], Genotyping, Exome sequencing, Genetics, biology, Odds ratio, genetics [Creutzfeldt-Jakob Syndrome], 030104 developmental biology, Genetic Loci, epidemiology [Genetic Predisposition to Disease], biology.protein, genetics [Polymorphism, Single Nucleotide], Neurology (clinical), 030217 neurology & neurosurgery, Genome-Wide Association Study, Human
Abstract: Background Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. Methods We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. Findings Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17–1·30], p=2·68 × 10 −15; heterozygous model p=1·01 × 10 −135), STX6 (rs3747957; OR 1·16 [1·10–1·22], p=9·74 × 10 −9), and GAL3ST1 (rs2267161; OR 1·18 [1·12–1·25], p=8·60 × 10 −10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. Interpretation We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. Funding Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.
Published: 2020
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42. Additional file 3 of Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Author: Lehmann, Sylvain, Dumurgier, Julien, Ayrignac, Xavier, Marelli, Cecilia, Alcolea, Daniel, Ormaechea, Juan Fortea, Thouvenot, Eric, Delaby, Constance, Hirtz, Christophe, Vialaret, Jérôme, Ginestet, Nelly, Bouaziz-Amar, Elodie, Jean-Louis Laplanche, Labauge, Pierre, Paquet, Claire, Lleo, Alberto, and Gabelle, Audrey
Subjects: lipids (amino acids, peptides, and proteins)
Abstract: Additional file 3 : Sup-Figure 1. CSF Aβ42 and Aβ40 in Non-AD and AD populations with regards to ApoE status Mean-centered values of CSF Aβ42 (panels A-C) and Aβ40 (panels D-F) in total (all), NAD and AD population with regards to ApoE4 allele presence (+) or absence (-). Panels G-I illustrate the difference in Aβ40 between AD and NAD in the population with the ApoE status determine, in the total (all), ApoE4 allele presence (+) or absence (-).
Published: 2020
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43. Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders

Author: Hugues Chabriat, Siham Dekimeche, Catherine Belin, Julien Dumurgier, Stéphane Goutagny, Lisette Volpe-Gillot, Elodie Bouaziz-Amar, Florence Mahieux, Frank Questel, Bénédicte Defontaines, Emmanuel Cognat, Julien Azuar, Victor Haddad, Jacques Hugon, Antonio Texeira, Pierre-Olivier Sellier, Claire Paquet, and Jean-Louis Laplanche
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Population, tau Proteins, Disease, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Humans, Longitudinal Studies, education, Aged, Aged, 80 and over, education.field_of_study, Amyloid beta-Peptides, business.industry, General Neuroscience, Amyloidosis, Snap, General Medicine, Middle Aged, medicine.disease, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Cohort, Disease Progression, Biomarker (medicine), Female, France, Geriatrics and Gerontology, medicine.symptom, Cognition Disorders, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: Background CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels of amyloid and neurodegeneration pathologies. Objective To investigate the distribution of AD biomarker profiles from patients suffering from cognitive disorders. Methods We analyzed 3001 patients with cognitive disorders and referred by 18 French memory clinics located in and around Paris. Patients were classified as normal, amyloidosis (A+/N-), amyloidosis and neurodegeneration (A+/N+) or suspected non-AD pathophysiology (SNAP), according to their CSF levels of biomarkers. Analysis were performed for the overall population and stratified by gender, age quintiles, and Mini-Mental State Examination (MMSE) score quintiles. Results were compared to previous findings in cohorts of healthy elderly adults. Results 37% of the sample were classified as A+/N+, 22% were classified A+/N-, and 15% as SNAP. The A+/N+ profile was associated with female gender, advanced age, and lower MMSE score, while the A+/N-profile was observed more frequently in men and the distribution was stable across age and MMSE. The SNAP profile showed no association with gender or age, was less frequent in patients with lower MMSE, and had a lower repartition than the one previously reported in asymptomatic populations. Conclusions While A+/N+ patients had the clinical characteristics typically observed in AD, A+/N-patients had a different epidemiological pattern (higher frequency in men, no association with advanced age or lower MMSE). The SNAP profile was less frequent than previously reported in the general elderly population, suggesting that this profile is not a frequent cause of memory impairment in this population.
Published: 2018
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44. Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers

Author: Olivier Vercruysse, Claire Paquet, Audrey Gabelle, Xavier Delbeuck, Frederic Blanc, David Wallon, Julien Dumurgier, Eloi Magnin, Olivier Martinaud, Barbara Jung, Olivier Bousiges, Sylvain Lehmann, Constance Delaby, Muriel Quillard-Murain, Katell Peoc`h, Jean-Louis Laplanche, Elodie Bouaziz-Amar, Didier Hannequin, Bernard Sablonniere, Luc Buee, Jacques Hugon, Susanna Schraen, Florence Pasquier, Stephanie Bombois, null for the e-PLM group, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Strasbourg (UNISTRA), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Plateforme de Protéomique Clinique, CHU Saint-Eloi, Université Paris Diderot - Paris 7 (UPD7), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], tau Proteins, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Diagnostic Errors, Phosphorylation, Vascular dementia, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Aged, Retrospective Studies, Hippocampal sclerosis, Amyloid beta-Peptides, business.industry, Brain, medicine.disease, Peptide Fragments, 3. Good health, Neurology, Mood disorders, Biomarker (medicine), Female, Neurology (clinical), Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies, Frontotemporal dementia
Abstract: Background: Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD). Objective: The aim of this study was to test the hypothesis of misdiagnoses for these patients. Method: Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF Aβ1-42, T-tau and P-tau biomarkers and clinical follow-up, were included. Clinical and imaging data were reviewed by an independent board, from baseline (visit with clinical evaluation and CSF analysis) to the end of the follow-up, for a final diagnosis. Results: In the e-PLM cohort of 1098 AD patients with CSF analysis, 37 (3.3%) patients (20 with AD dementia core clinical criteria and 17 with AD-MCI core clinical criteria) had normal CSF biomarker profile and a clinical follow-up. All patients presented with episodic memory impairment and 27 (73%) had medial temporal lobe atrophy on MRI-scan. After a median follow-up of 36 months (range 7-74), the final diagnosis was AD MCI or dementia for 9 (24%) patients, and unlikely due to AD for 28 (76%) patients. A misdiagnosis was corrected in 18 (49%) patients (mood disorders, non-AD degenerative dementia, vascular cognitive impairment, alcohol cognitive disorders, temporal epilepsy and hippocampal sclerosis), and 10 (27%) patients had cognitive disorders of undetermined etiology. Conclusion: AD diagnosis (MCI or dementia) with normal CSF biomarkers is a rare condition. A clinical follow- up is particularly recommended to consider an alternative diagnosis.
Published: 2018
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45. Primary Osteoporosis in Young Adults: Genetic Basis and Identification of Novel Variants in Causal Genes

Author: Philippe Orcel, Jean-Louis Laplanche, Thomas Funck-Brentano, Elise Schaefer, Pascale Guillot, Corinne Collet, Bertrand Isidor, Rose-Marie Javier, Giulia Tueur, Manon Ricquebourg, Marine Delecourt, Martine Cohen-Solal, and Agnès Ostertag
Subjects: 0301 basic medicine, Bone mineral, Genetics, Oncology, Candidate gene, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Osteoporosis, LRP5, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Cohort, PLS3, Medicine, Missense mutation, Orthopedics and Sports Medicine, Young adult, business, 030217 neurology & neurosurgery
Abstract: Genetic determinants contribute to osteoporosis and enhance the risk of fracture. Genomewide association studies of unselected population-based individuals or families have identified polymorphisms in several genes related to low bone density, but not in osteoporotic patients with Z-score
Published: 2017
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46. Les biomarqueurs du liquide cérébro-spinal dans la maladie d’Alzheimer : un outil de recherche utile dans la pratique clinique courante des consultations mémoire pour les cas complexes

Author: Katell Peoc'h, F. Blanc, Julien Dumurgier, O. Bousiges, A. Gabelle, Didier Hannequin, Sylvain Lehmann, Elodie Bouaziz-Amar, pour le groupe ePLM, F. Pasquier, Jacques Hugon, C. Miguet-Alfonsi, B. Jung, D. Wallon, E. Magnin, Claire Paquet, M. Quillard, Jean-Louis Laplanche, and S. Bombois
Subjects: 0301 basic medicine, Gynecology, medicine.medical_specialty, Amyloid, biology, business.industry, Tau protein, Gastroenterology, Neurofibrillary tangle, Disease, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Csf biomarkers, Internal Medicine, medicine, biology.protein, Total Tau Protein, Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract: The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorite de sante) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases.
Published: 2017
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47. Lithium response in bipolar disorders and core clock genes expression

Author: Bruno Etain, Frank Bellivier, Cindie Courtin, Thomas Morvillers, Pierre A. Geoffroy, Emmanuel Curis, Jeverson Moreira, Jean-Louis Laplanche, Cynthia Marie-Claire, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fondation FondaMental [Créteil], Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), 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)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Variabilité de réponse aux Psychotropes (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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), and 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)
Subjects: Adult, Male, medicine.medical_specialty, Bipolar Disorder, Lithium (medication), Gene Expression, Biology, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Antimanic Agents, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, medicine, Humans, Bipolar disorder, Circadian rhythm, ComputingMilieux_MISCELLANEOUS, Biological Psychiatry, Circadian Rhythm Signaling Peptides and Proteins, Lithium carbonate, Middle Aged, medicine.disease, 030227 psychiatry, 3. Good health, Cell biology, CLOCK, Psychiatry and Mental health, Endocrinology, chemistry, Lithium Compounds, Female, sense organs, 030217 neurology & neurosurgery, medicine.drug
Abstract: We examine whether the lithium response is associated with changes in the expression of core clock genes.The effect of a therapeutic concentration of lithium (1 mM) on the expression levels of 17 circadian genes was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of bipolar disorder patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) was conducted at 2, 4 and 8 days (d2, d4 and d8) with and without lithium exposure.At d2, in ER only, BHLHE41, RORA, PER1, ARNTL, CRY2, BHLHE40 and CSNK1D were upregulated, whereas NR1D1 was downregulated. At d4, in ER only, CRY1 was downregulated. At d8, in NR only, GSK3β was upregulated and DBP, TIMELESS and CRY1 were downregulated. Significant Group × Lithium interactions existed for NR1D1 at d2 (P = 0.02), and CRY1 at d4 (P = 0.02). Longitudinal analyses showed differential temporal evolutions between NR and ER (significant Time × Group interaction) for PER3, NR1D1, DBP, RORA, CSNK1D and TIMELESS; and a significant Time × Lithium interaction for NR1D1. Coexpression data analyses suggested distinct groups of circadian genes concurrently modulated by lithium.In LCLs, lithium influences expression of circadian genes with differences in amplitude and kinetics according to the patient's lithium response status.
Published: 2017
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48. Amplification techniques and diagnosis of prion diseases

Author: Stéphane Haïk, Jean-Louis Laplanche, Jean-Philippe Brandel, Etienne Levavasseur, Audrey Culeux, P. Lamy, Arlette Welaratne, Katarina Grznarova, A. Denouel, Nicolas Privat, 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 [AP-HP], and 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)
Subjects: Pathology, medicine.medical_specialty, Diagnostic methods, Sporadic CJD, business.industry, animal diseases, [SDV]Life Sciences [q-bio], Creutzfeldt-Jakob Syndrome, nervous system diseases, 3. Good health, Variant cjd, Prion Diseases, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Neurology, Molecular Diagnostic Techniques, mental disorders, medicine, Protein Misfolding Cyclic Amplification, Humans, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Protein misfolding cyclic amplification assay (PMCA) and real-time quaking-induced conversion (RT-QuIC) are two amplification techniques based on the ability of PrPsc to induce a conformational change in PrP allowing the detection of minute amounts of PrPsc in body fluids or tissues. PMCA and RT-QuIC have different ability to amplify PrPsc from sporadic, variant and genetic forms of Creutzfeldt-Jakob disease (CJD). PMCA readily amplifies PrPsc from variant CJD (vCJD) tissue while RT-QuIC easily amplifies PrPsc from sporadic CJD (sCJD) patient tissues. In terms of diagnosis, this implies the possibility of distinguishing vCJD from sCJD and explains the wider use of RT-QuIC given the respective frequencies of vCJD and sCJD. The sensitivity values of RT-QuIC for the diagnosis of sCJD are comparable or higher than those of the other tests (EEG, MRI, detection of 14-3-3 or tau proteins in cerebrospinal fluid) but with a specificity close to 100%. These new diagnostic methods could also be useful for the diagnosis of other neurodegenerative diseases.
Published: 2019
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49. The neurobehavioral effects of the designer drug naphyrone - an experimental investigation with pharmacokinetics and concentration/effect relationship in mice

Author: Nadia Benturquia, Camille Gamblin, Lucie Chevillard, Gilles Morineau, Bruno Mégarbane, Huixiong Chen, Elodie Bouaziz-Amar, Matthias E. Liechti, Jacques Callebert, Mélanie Etheve-Quelquejeu, Olivier Roussel, Jean-Louis Laplanche, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Criminelle de la Gendarmerie Nationale (IRCGN), IRCGN, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University Hospital Basel [Basel], University of Basel (Unibas), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Chevillard, Lucie, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Équipe Mouvement des Systèmes Anthropomorphes (LAAS-GEPETTO), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Lariboisière-Fernand-Widal [APHP], Service de Biochimie et de Biologie Moléculaire [AP-HP Hôpital Lariboisière] (Inserm U942), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique (NAVVEC - UM 81 (UMR 8206/ U705)), Université Paris Diderot - Paris 7 (UPD7)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Pyrrolidines, Pyrovalerone, Prefrontal Cortex, Designer Drugs, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Pharmacokinetics, Dopamine, Internal medicine, Pentanones, medicine, Animals, Prefrontal cortex, Spatial Memory, Pharmacology, Dose-Response Relationship, Drug, business.industry, Illicit Drugs, Anhedonia, 030227 psychiatry, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Monoamine neurotransmitter, Endocrinology, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Naphyrone, Serotonin, medicine.symptom, business, 030217 neurology & neurosurgery, Locomotion, medicine.drug
Abstract: The recreational use of naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. To investigate naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. We studied naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled naphyrone pharmacokinetics and concentration/locomotor effect relationship. Both naphyrone administration patterns induced time-dependent increases in locomotor activity (p
Published: 2019
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50. Increased plasma levels of high mobility group box 1 protein in patients with bipolar disorder: A pilot study

Author: Anne Blanchard, Emmanuel Curis, Elodie Bouaziz-Amar, Frank Bellivier, Bruno Etain, Aude Jacob, Cynthia Marie-Claire, Jean-Louis Laplanche, Cindie Courtin, Variabilité de réponse aux Psychotropes (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), Laboratoire de biomathématiques, EA 7537 [Paris] (BioSTM), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5), AP-HP, GH Saint-Louis – Lariboisière – F. Widal, Département de biostatistiques et d'informatique médicales, Paris, France, GH Saint-Louis – Lariboisière – F. Widal, Département de Biochimie et Biologie moléculaire, Paris, France, AP-HP, GH Saint-Louis – Lariboisière – F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris Cedex 10, France, Fondation FondaMental [Créteil], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Marie-Claire, Cynthia
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Pilot Projects, Gastroenterology, Plasma, 0302 clinical medicine, MESH: HMGB1 Protein, MESH: Bipolar Disorder, Immunology and Allergy, HMGB1 Protein, HMGB1, MESH: Middle Aged, biology, Middle Aged, Peripheral, Cytokine, Neurology, MESH: Young Adult, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, Bipolar disorder, Immunology, Inflammation, chemical and pharmacologic phenomena, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, Young Adult, Text mining, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, In patient, MESH: Adolescent, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Pilot Projects, MESH: Male, 030104 developmental biology, High-mobility group, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, MESH: Biomarkers, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, Biomarkers
Abstract: International audience; High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that emerges as a promising peripheral marker of inflammation. HMGB1 and C-reactive protein levels were assessed in plasma of control subjects and remitted patients with bipolar disorder (BD). HMGB1 levels were significantly higher in patients with BD as compared to control subjects whereas C-reactive protein levels did not differ between the two groups. No significant effect of potential covariates was identified. The results of this pilot study suggest that HMGB1 might be a specific peripheral marker of inflammation in BD.
Published: 2019
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