ORCID Profile
0000-0001-5473-3697
Current Organisations
INSERM
,
Université Paris Descartes
,
Université Paris-Est Créteil Val de Marne Faculté de médecine
,
Assistance Publique Hôpitaux de Paris
,
Fondation FondaMental
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Publications
Analysis of X chromosome inactivation in autism spectrum disorders
Publisher: Wiley
Date: 22-08-2008
DOI: 10.1002/AJMG.B.30688
Childhood trauma moderates schizotypy-related brain morphology: Analyses of 1,182 healthy individuals from the ENIGMA Schizotypy working group
Publisher: Cold Spring Harbor Laboratory
Date: 28-11-2022
DOI: 10.1101/2022.11.22.22282598
Abstract: Schizotypy represents an index of psychosis-proneness in the general population often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. We addressed this question using data from a total of 1,182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical grey matter volume and cortical thickness were determined. A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of thicker bilateral medial orbitofrontal gyri, right rostral anterior cingulate gyrus, left temporal pole, left insula, and thinner left paracentral lobule directly associated with increasing levels of schizotypy. In addition, thinner left postcentral, superior parietal and lingual gyri, as well as thicker left caudal middle frontal gyrus and smaller left thalamus and right caudate were associated with increasing levels of childhood trauma exposure. These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in in iduals exposed to high levels of trauma.
Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder
Publisher: Research Square Platform LLC
Date: 26-06-2023
DOI: 10.21203/RS.3.RS-3068352/V1
Abstract: The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi + Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p 1x10 − 4 values, including HAS3 , CNTNAP5 and NFIB . Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP’s age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4 , XKR4 , NRXN1 , NRG1/3 and GRK5 . Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
Publisher: Elsevier BV
Date: 2022
Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder
Publisher: Oxford University Press (OUP)
Date: 21-06-2016
DOI: 10.1093/HMG/DDW181
Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study
Publisher: Elsevier BV
Date: 03-2016
Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Publisher: Public Library of Science (PLoS)
Date: 24-10-2013
Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 20-06-2017
DOI: 10.1038/TP.2017.115
Abstract: Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient s les worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD ( P =4.42 × 10 −7 ) and PKP4 ( P =8.67 × 10 −7 ) and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P FDR =0.019 FDR, false discovery rate). Prior studies have implicated DPYD , PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP ( r g =0.28 [ P =2.99 × 10 −3 ]), SCZ ( r g =0.34 [ P =4.37 × 10 −5 ]) and MDD ( r g =0.57 [ P =1.04 × 10 −3 ]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study
Publisher: Elsevier BV
Date: 08-2022
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 22-05-2017
The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism
Publisher: Springer Science and Business Media LLC
Date: 13-06-2014
DOI: 10.1038/NCOMMS5074
Abstract: Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects ( P ≤2.40E−09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched ( P ≤3.83E−23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network ( P ≤4.16E−04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions.
Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
Publisher: Elsevier BV
Date: 06-2018
A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder
Publisher: Springer Science and Business Media LLC
Date: 14-10-2011
T145. ALTERATIONS IN SUPERFICIAL WHITE MATTER IN THE FRONTAL CORTEX IN SCHIZOPHRENIA: A DWI STUDY USING A NOVEL ATLAS
Publisher: Oxford University Press (OUP)
Date: 04-2018
Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
Publisher: Springer Science and Business Media LLC
Date: 29-11-2021
DOI: 10.1038/S41398-021-01702-2
Abstract: Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between in iduals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi + Gen www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility
Publisher: Springer Science and Business Media LLC
Date: 09-04-2013
DOI: 10.1038/MP.2013.37
Strategies and foundations for scientific discovery in longitudinal studies of bipolar disorder
Publisher: Wiley
Date: 18-03-2022
DOI: 10.1111/BDI.13198
Abstract: Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical s les with cross‐sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life‐story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.
Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1
Publisher: Springer Science and Business Media LLC
Date: 25-08-2016
DOI: 10.1007/S12035-016-0041-X
Abstract: Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders however, when s le size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different s les. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P
Corpus callosum area in patients with bipolar disorder with and without psychotic features: an international multicentre study
Publisher: CMA Joule Inc.
Date: 09-2015
DOI: 10.1503/JPN.140262
Abstract: Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre s le of patients with BD and healthy controls. We analyzed anatomic T1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. We found small to medium effect sizes, and there was no calibration technique among the sites. Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD.
Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
Publisher: Springer Science and Business Media LLC
Date: 04-12-2015
DOI: 10.1007/S12035-015-9559-6
Abstract: Reelin (RELN) is identified as a risk gene for major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). However, the role of its downstream signaling molecule, the low-density lipoprotein receptor-related protein 8 (LRP8) in these illnesses is still unclear. To detect whether LRP8 is a susceptibility gene for SCZ and BPD, we analyzed the associations of single nucleotide polymorphisms (SNPs) in LRP8 in a total of 47,187 subjects (including 9379 SCZ patients 6990 BPD patients and 12,556 controls in a screening s le, and 1397 SCZ families, 3947 BPD patients, and 8387 controls in independent replications), and identified a non-synonymous SNP rs5174 in LRP8 significantly associated with SCZ and BPD as well as the combined psychosis phenotype (P
Altering the course of schizophrenia: progress and perspectives
Publisher: Springer Science and Business Media LLC
Date: 04-03-2016
DOI: 10.1038/NRD.2016.28
Abstract: Despite a lack of recent progress in the treatment of schizophrenia, our understanding of its genetic and environmental causes has considerably improved, and their relationship to aberrant patterns of neurodevelopment has become clearer. This raises the possibility that 'disease-modifying' strategies could alter the course to - and of - this debilitating disorder, rather than simply alleviating symptoms. A promising window for course-altering intervention is around the time of the first episode of psychosis, especially in young people at risk of transition to schizophrenia. Indeed, studies performed in both in iduals at risk of developing schizophrenia and rodent models for schizophrenia suggest that pre-diagnostic pharmacotherapy and psychosocial or cognitive-behavioural interventions can delay or moderate the emergence of psychosis. Of particular interest are 'hybrid' strategies that both relieve presenting symptoms and reduce the risk of transition to schizophrenia or another psychiatric disorder. This Review aims to provide a broad-based consideration of the challenges and opportunities inherent in efforts to alter the course of schizophrenia.
Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study
Publisher: Research Square Platform LLC
Date: 03-10-2023
Genome-wide association study of obsessive-compulsive disorder
Publisher: Springer Science and Business Media LLC
Date: 14-08-2012
DOI: 10.1038/MP.2012.85
The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder.
Publisher: Informa UK Limited
Date: 03-08-2020
DOI: 10.1080/15622975.2018.1492734
Abstract: To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disorder (BD) on cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of differential expression in in iduals with BD. To use the GES to identify new drugs for BD using Connectivity Map (CMap).
Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders
Publisher: Cold Spring Harbor Laboratory
Date: 17-08-2020
DOI: 10.1101/2020.08.13.249813
Abstract: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. We conducted the largest to date genome-wide genotype–by–sex (GxS) interaction of risk for these disorders, using 85,735 cases (33,403 SCZ, 19,924 BIP, 32,408 MDD) and 109,946 controls from the Psychiatric Genomics Consortium (PGC) and iPSYCH. Across disorders, genome-wide significant SNP-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815 p =3.2×10 −8 ), that interacts with sodium otassium-transporting ATPase enzymes implicating neuronal excitability. Three additional loci showed evidence ( p ×10 −6 ) for cross-disorder GxS interaction (rs7302529, p =1.6×10 −7 rs73033497, p =8.8×10 −7 rs7914279, p =6.4×10 −7 ) implicating various functions. Gene-based analyses identified GxS interaction across disorders ( p =8.97×10 −7 ) with transcriptional inhibitor SLTM . Most significant in SCZ was a MOCOS gene locus (rs11665282 p =1.5×10 −7 ), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509 p =1.1×10 −7 ) in a locus containing IDO2 , a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant GxS of genes regulating vascular endothelial growth factor (VEGF) receptor signaling in MDD ( p FDR .05). In the largest genome-wide GxS analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development, immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway enrichment levels.
Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette’s Syndrome and OCD
Publisher: American Psychiatric Association Publishing
Date: 2015
Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive per
Publisher: Royal College of Psychiatrists
Date: 02-2016
DOI: 10.1192/BJP.BP.114.156976
Abstract: Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippoc al volume ( n = 5775) and cognitive performance ( n = 342) among healthy in iduals. Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48 bipolar disorder P = 5.85×10 –5 ). Follow-up studies across multiple independent s les confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility ( P = 3.54×10 –8 ). Further exploratory analysis revealed that rs6088662 is also associated with hippoc al volume and cognitive performance in healthy in iduals. Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
Publisher: Frontiers Media SA
Date: 31-05-2018
Correction: Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
Publisher: Springer Science and Business Media LLC
Date: 11-07-2022
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study
Publisher: Wiley
Date: 28-06-2018
DOI: 10.1111/BDI.12659
Childhood trauma moderates schizotypy-related brain morphology: analyses of 1182 healthy individuals from the ENIGMA schizotypy working group
Publisher: Cambridge University Press (CUP)
Date: 20-10-2023
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial
Publisher: Elsevier BV
Date: 2010
Clinical staging in psychiatry: a cross-cutting model of diagnosis with heuristic and practical value
Publisher: Royal College of Psychiatrists
Date: 04-2013
DOI: 10.1192/BJP.BP.112.110858
Abstract: Staging models are used routinely in general medicine for potentially serious or chronic physical disorders such as diabetes, arthritis and cancers, describing the links between biomarkers, clinical phenotypes and disease extension, and promoting a personalised or stratified medicine approach to treatment planning. Clinical staging involves a detailed description of where an in idual exists on a continuum of disorder progression from stage 0 (an at-risk or latency stage) through to stage IV (late or end-stage disease). The approach is popular owing to its clinical utility and is increasingly being applied in psychiatry. The concept offers an informed approach to research and the active promotion of indicated prevention and early intervention strategies. We suggest that for young persons with emerging bipolar disorder, such transdiagnostic staging models could provide a framework that better reflects the developmental psychopathology and matches the complex longitudinal inter-relationships between subsyndromal and syndromal mood, psychotic and other disorders.
Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa
Publisher: American Psychiatric Association Publishing
Date: 09-2017
Characterization of Age and Polarity at Onset in Bipolar Disorder
Publisher: Cold Spring Harbor Laboratory
Date: 16-04-2021
DOI: 10.1101/2021.04.16.21251163
Abstract: Studying the phenotypic and genetic characteristics of age and polarity at onset (AAO, PAO) in bipolar disorder (BD) can provide new insights into disease pathology and facilitate the development of screening tools. To examine the genetic architecture of AAO and PAO and their association with BD disease characteristics. Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (N=12977) and PAO (N=6773) were conducted in BD patients of 34 cohorts and a replication s le (N=2237). The association of onset with disease characteristics was investigated in two of these cohorts. Earlier AAO was associated with an increased risk of psychotic symptoms, suicidality, and fewer episodes. A depressive onset correlated with lifetime suicidality and a manic onset with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in SNV-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased polygenic scores for autism spectrum disorder (β=-0.34 years, SE=0.08), major depression (β=-0.34 years, SE=0.08), schizophrenia (β=-0.39 years, SE=0.08), and educational attainment (β=-0.31 years, SE=0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. AAO and PAO are associated with indicators of BD severity. In iduals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents, and phenotype definitions introduce significant heterogeneity, affecting analyses. In the largest study to systematically characterize age at onset (N=12977) and polarity at onset (N=6773) in bipolar disorder, we describe an association between illness onset characteristics and indicators of severity, confirming their clinical relevance. Our study shows that that early illness onset is associated with genetic liability for a broad range of psychiatric disorders. However, we also highlight systematic differences in age at onset across cohorts, continents, and phenotype definitions. This heterogeneity results in reduced heritability and affects genetic analyses, underscoring the need for the development of standardized phenotype definitions.
Patterns of pharmacotherapy for bipolar disorder: A GBC survey
Publisher: Wiley
Date: 18-07-2023
DOI: 10.1111/BDI.13366
Abstract: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized in iduals with BD in North America, Europe, and Australia. Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. In idual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns. This study included 10,351 in iduals from North America ( n = 3985), Europe ( n = 3822), and Australia ( n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60% vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD.
Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report
Publisher: Public Library of Science (PLoS)
Date: 19-06-2013
Analysis of shared heritability in common disorders of the brain
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-06-2018
Abstract: Consistent classification of neuropsychiatric diseases is problematic because it can lead to misunderstanding of etiology. The Brainstorm Consortium examined multiple genome-wide association studies drawn from more than 200,000 patients for 25 brain-associated disorders and 17 phenotypes. Broadly, it appears that psychiatric and neurologic disorders share relatively little common genetic risk. However, different and independent pathways can result in similar clinical manifestations (e.g., psychosis, which occurs in both schizophrenia and Alzheimer's disease). Schizophrenia correlated with many psychiatric disorders, whereas the immunopathological affliction Crohn's disease did not, and posttraumatic stress syndrome was also largely independent of underlying traits. Essentially, the earlier the onset of a disorder, the more inheritable it appeared to be. Science , this issue p. eaap8757
Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder
Publisher: American Medical Association (AMA)
Date: 09-11-2017
Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
Publisher: Springer Science and Business Media LLC
Date: 15-05-2017
DOI: 10.1038/NG.3863
Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations
Publisher: Oxford University Press (OUP)
Date: 24-05-2014
Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders
Publisher: Elsevier BV
Date: 05-2014
Revealing the complex genetic architecture of obsessive–compulsive disorder using meta-analysis
Publisher: Springer Science and Business Media LLC
Date: 08-2017
DOI: 10.1038/MP.2017.154
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Publisher: Springer Science and Business Media LLC
Date: 11-08-2202
DOI: 10.1038/NG.2711
Related Organisations
Université Paris-Est Créteil Val De Marne Faculté De Médecine
Location: France
Related Funding Activities
No related grants have been discovered for Marion LEBOYER.