Boris Chaumette
French Institute of Health and Medical Research
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Featured researches published by Boris Chaumette.
Schizophrenia Research | 2014
Oussama Kebir; Boris Chaumette; Mar Fatjó-Vilas; Amirthagowri Ambalavanan; Nicolas Ramoz; Lan Xiong; Fayçal Mouaffak; Bruno Millet; Nematollah Jaafari; Lynn E. DeLisi; Douglas F. Levinson; Ridha Joober; Lourdes Fañanás; Guy A. Rouleau; Caroline Dubertret; Marie-Odile Krebs
BACKGROUND Histone deacetylases (HDACs) are key enzymes of histone acetylation, and abnormalities in histone modifications and in the level of HDAC proteins have been reported in schizophrenia. The objective of the present study was to systematically test the HDAC genes for its association with schizophrenia. METHODS A family-based genetic association study (951 Caucasian subjects in 313 nuclear families) using 601 tag-single nucleotide polymorphisms in HDAC genes was conducted followed by a replication study of top-ranked markers in a sample of 1427 Caucasian subjects from 241 multiplex families and 176 trios. Epistasis interaction was tested by using the pedigree-based generalized multifactor dimensionality reduction (GMDR). Furthermore, we analyzed exome sequencing data of 1134 subjects for detection of rare mutations in HDAC genomic regions. RESULTS In the exploratory study, ten markers were in significant association with schizophrenia (P<0.01). One maker rs14251 (HDAC3) was replicated (P=0.04) and remained significant in the whole sample (P=0.004). GMDR identified that a significant three-locus interaction model was detected involving rs17265596 (HDAC9), rs7290710 (HDAC10) and rs7634112 (HDAC11) with a good testing accuracy (0.58). No rare mutations were found associated with schizophrenia. CONCLUSION This first exploratory systematic study of the HDAC genes provides consistent support for the involvement of the HDAC3 gene in the etiology of schizophrenia. A statistical epistatic interaction between HDAC9, HDAC10, and HDAC11 was detected and seems biologically plausible.
PLOS ONE | 2017
Fabrice Rivollier; Boris Chaumette; Narjes Bendjemaa; Mélanie Chayet; Bruno Millet; Nematollah Jaafari; Amina Barhdadi; Louis-Philippe Lemieux Perreault; Sylvie Provost; Marie-Pierre Dubé; Raphaël Gaillard; Marie-Odile Krebs; Oussama Kebir
Background In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis. Methods From 247 individuals born from mothers exposed to DES, we selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to DES. We performed a methylome-wide association study using HumanMethylation450 DNA Analysis BeadChip® in peripheral blood. We analyzed methylation changes at individual CpGs or regions in exposed (n = 37) versus unexposed individuals (n = 32). We also compared exposed individuals with (n = 7) and without psychosis (n = 30). Results There were more individuals with schizophrenia in the DES-exposed group. We found no significant differences between exposed and unexposed individuals with respect to differentially methylated CpGs or regions. The largest difference was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9). Compared to exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein 57 (ZFP57). Conclusions In utero exposure to DES was not associated with methylation changes at specific CpG or regions. In exposed individuals, however, psychosis was associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity.
Translational Psychiatry | 2018
Oussama Kebir; Boris Chaumette; Marie-Odile Krebs
Conversion to psychosis is a longitudinal process during which several epigenetic changes have been described. We tested the hypothesis that epigenetic variability in the methylomes of ultra-high risk (UHR) individuals may contribute to the risk of conversion. We studied a longitudinal cohort of UHR individuals (n = 39) and compared two groups (converters, n = 14 vs. non-converters, n = 25). A longitudinal methylomic study was conducted using Infinium HumanMethylation450 BeadChip covering half a million cytosine–phosphate–guanine (CpG) sites across the human genome from whole-blood samples. We used two statistical methods to investigate the variability of methylation probes. (i) The search for longitudinal variable methylation probes (VMPs) based on median comparisons identified two VMPs in converters only. The first CpG was located in the MACROD2 gene and the second CpG was in an intergenic region at 8q24.21. (ii) The detection of outliers using variance analysis related to private epimutations identified a dozen CpGs in converters only and highlighted two genes (RAC1 and SPHK1) from the sphingolipid signaling pathway. Our study is the first to support increased methylome variability during conversion to psychosis. We speculate that stochastic factors could increase DNA methylation variability and have a role in the complex pathophysiology of conversion to psychosis as well as in other psychiatric diseases.
Schizophrenia Bulletin | 2018
Boris Chaumette; Oussama Kebir; Juliette Pouch; Bertrand Ducos; Fekrije Selimi; Raphaël Gaillard; Marie-Odile Krebs
The biological processes associated with the onset of schizophrenia remain largely unknown. Current hypotheses favor gene × environment interactions as supported by our recent report about DNA methylation changes during the onset of psychosis. Here, we conducted the first longitudinal transcriptomic analysis of blood samples from 31 at-risk individuals who later converted to psychosis and 63 at-risk individuals who did not. Individuals were followed for a maximum of 1 year. Blood samples were collected at baseline and at the end of follow-up and individuals served as their own controls. Differentially expressed genes between the 2 groups were identified using the RNA sequencing of an initial discovery subgroup (n = 15 individuals). The most promising results were replicated using high-throughput real-time qPCR in the whole cohort (n = 94 individuals). We identified longitudinal changes in 4 brain-expressed genes based on RNAseq analysis. One of these genes (CPT1A) was replicated in the whole cohort. The previously observed hypermethylation in NRP1 and GSTM5 during the onset of psychosis correlated with a decrease in corresponding gene expression. RNA sequencing also identified 2 co-expression networks that were impaired after conversion compared with baseline-the Wnt pathway including AKT1, CPT1A and semaphorins, and the Toll-like receptor pathway, related to innate immunity. This longitudinal study of transcriptomic changes in individuals with at-risk mental state revealed alterations during conversion to psychosis in pathways and genes relevant to schizophrenia. These results may be a first step toward better understanding psychosis onset. They may also help to identify new biomarkers and targets for disease-modifying therapeutic strategies.
Schizophrenia Bulletin | 2018
Oussama Kebir; Boris Chaumette; Marie-Odile Krebs
Abstract Background Epigenetics is hypothesized to mediate the interplay between genes and environment leading to the onset of psychosis Methods We performed a longitudinal prospective study of genomic DNA methylation during psychotic transition in help-seeking young individuals referred to a specialized outpatient unit for early detection of psychosis and enrolled in a 1-year follow-up (n=39). We used Infinium HumanMethylation450 BeadChip array after bisulfite conversion and analyzed longitudinal variations in methylation at 411947 cytosine–phosphate–guanine (CpG) sites. Results We observed that conversion to psychosis was not associated with a global change in methylation and there was no individual CpG significantly associated with psychotic transition. By contrast, we found that conversion to psychosis was associated with specific methylation changes in genes involved in axon guidance, as well as genes of the IL-17 pathway and the glutathione-S-transferase family. Discussion Alterations in oxidative stress regulation, axon guidance and in inflammatory pathways could represent multiple theaters for the disruption in homeostasis that accompanies the emergence of full-blown psychosis.
Frontiers in Molecular Neuroscience | 2018
Alfredo Bellon; Amelie Wegener; Adam R. Lescallette; Michael Valente; Seung-Kwon Yang; Robert Gardette; Julien Matricon; Fayçal Mouaffak; Paula Watts; Lene Vimeux; Jong K. Yun; Yuka Imamura Kawasawa; Gary A. Clawson; Elisabeta Blandin; Boris Chaumette; Thérèse M. Jay; Marie-Odile Krebs; Vincent Feuillet; Anne Hosmalin
Despite progress, our understanding of psychiatric and neurological illnesses remains poor, at least in part due to the inability to access neurons directly from patients. Currently, there are in vitro models available but significant work remains, including the search for a less invasive, inexpensive and rapid method to obtain neuronal-like cells with the capacity to deliver reproducible results. Here, we present a new protocol to transdifferentiate human circulating monocytes into neuronal-like cells in 20 days and without the need for viral insertion or reprograming. We have thoroughly characterized these monocyte-derived-neuronal-like cells (MDNCs) through various approaches including immunofluorescence (IF), flow cytometry, qRT-PCR, single cell mRNA sequencing, electrophysiology and pharmacological techniques. These MDNCs resembled human neurons early in development, expressed a variety of neuroprogenitor and neuronal genes as well as several neuroprogenitor and neuronal proteins and also presented electrical activity. In addition, when these neuronal-like cells were exposed to either dopamine or colchicine, they responded similarly to neurons by retracting their neuronal arborizations. More importantly, MDNCs exhibited reproducible differentiation rates, arborizations and expression of dopamine 1 receptors (DR1) on separate sequential samples from the same individual. Differentiation efficiency measured by cell morphology was on average 11.9 ± 1.4% (mean, SEM, n = 38,819 cells from 15 donors). To provide context and help researchers decide which in vitro model of neuronal development is best suited to address their scientific question,we compared our results with those of other in vitro models currently available and exposed advantages and disadvantages of each paradigm.
Psychoneuroendocrinology | 2016
Boris Chaumette; Oussama Kebir; Célia Mam-Lam-Fook; Yannick Morvan; Julie Bourgin; Marion Plaze; Raphaël Gaillard; Thérèse M. Jay; Marie-Odile Krebs
Journal of Inherited Metabolic Disease | 2018
Alice Kuster; Jean-Baptiste Arnoux; Magalie Barth; D. Lamireau; Nada Houcinat; Cyril Goizet; Bérénice Doray; Stéphanie Gobin; Manuel Schiff; Aline Cano; Daniel Amsallem; Christine Barnerias; Boris Chaumette; Marion Plaze; Abdelhamid Slama; Christine Ioos; Isabelle Desguerre; Anne-Sophie Lebre; Pascale de Lonlay; Laurence Christa
Journal of the American Academy of Child and Adolescent Psychiatry | 2018
Vladimir Ferrafiat; Boris Chaumette; Amirthagowri Ambalavanan; Priscille Gerardin; Claudine Laurent; David Cohen; Judith L. Rapoport; Guy A. Rouleau
European Psychiatry | 2016
Oussama Kebir; Boris Chaumette; Marie-Odile Krebs