Marion Leboyer - Academia.edu (original) (raw)

Papers by Marion Leboyer

Schizophrenia Bulletin Open, 2021

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) re... more Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients wa...

The Lancet Psychiatry, 2021

Molecular neurobiology, Sep 25, 2016

Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome... more Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample 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 samples. 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 meta = 5.72 × 10(-4)), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10(-16...

Social Psychiatry and Psychiatric Epidemiology, 2016

Purpose We sought to determine whether significant variation in the incidence of clinically relev... more Purpose We sought to determine whether significant variation in the incidence of clinically relevant psychoses existed at an ecological level in an urban French setting, and to examine possible factors associated with this variation. We aimed to advance the literature by testing this hypothesis in a novel population setting and by comparing a variety of spatial models. Methods We sought to identify all first episode cases of non-affective and affective psychotic disorders presenting in a defined urban catchment area over a 4 years period, over more than half a million person-years at-risk. Because data from geographic close neighbourhoods usually show spatial autocorrelation, we used for our analyses Bayesian modelling. We included small area neighbourhood measures of deprivation, migrants' density and social fragmentation as putative explanatory variables in the models. Results Incidence of broad psychotic disorders shows spatial patterning with the best fit for models that included both strong autocorrelation between neighbouring areas and weak autocorrelation between areas further apart. Affective psychotic disorders showed similar spatial patterning and were associated with the proportion of migrants/foreigners in the area (inverse correlation). In contrast, non-affective psychoses did not show spatial patterning. Conclusions At ecological level, the variation in the number of cases and the factors that influence this variation are different for non-affective and affective psychotic disorders. Important differences in results-compared with previous studies in different settings-point to the importance of the context and the necessity of further studies to understand these differences.

Psychologie Francaise, 1991

The British journal of psychiatry : the journal of mental science, Jan 3, 2015

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses s... more BackgroundBipolar 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.AimsWe 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.MethodTo 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 hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain ...

Frontiers in Bioscience, 2012

Introduction 3. Immuno-inflammatory markers in bipolar disorder 3.1. Abnormalities of the innate ... more Introduction 3. Immuno-inflammatory markers in bipolar disorder 3.1. Abnormalities of the innate and the adaptative system in bipolar disorder 3.2. C-reactive protein (crp) and bipolar disorder 3.3. Autoimmunity in bipolar disorder 3.4. The contribution of immunogenetics in bipolar disorder 4. The viral hypothesis 4.1. A winter/spring excess of birth in bipolar disorder 4.2. Viruses and bipolar disorder 5. The retroviral hypothesis: a new avenue of research? 6.

Psychological Medicine, 2005

Background. Executive dysfunctions in relatives of schizophrenic patients may be trait markers of... more Background. Executive dysfunctions in relatives of schizophrenic patients may be trait markers of genetic liability and thus help us to elucidate the aetiology of schizophrenia. As a large amount of data has been published, a synthesis through a meta-analysis was needed to demonstrate the existence of executive impairments in relatives of schizophrenic patients and to assess their magnitude.Method. We conducted a meta-analysis of articles that compared performances of controls and relatives of schizophrenic patients on the four tests most frequently used to assess executive functions: the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Stroop Test and the Verbal Fluency (VF) Test. When needed and possible, published data were supplemented with information from the authors. After assessing the homogeneity of the data, effect sizes were estimated and publication bias was tested by use of funnel plots.Results. Relatives of schizophrenic patients performed less well...

Psychological Medicine, 1997

Background. Previous studies have shown that individuals with autism show impaired performance on... more Background. Previous studies have shown that individuals with autism show impaired performance on tests of executive function (Ozonoff et al. 1991, 1993; Hughes & Russell, 1993; Hughes et al. 1994). There is also strong evidence for genetic involvement in autism (see Rutter, 1991 for review). If executive dysfunction is a core impairment in autism, then similar impairments are hypothesized to exist in a subtler form among the parents of autistic children.Methods. Forty parents of autistic children were compared with 40 parents of learning disabled children and 36 adults from unaffected families on three computerized tests of executive function. These tasks tapped attentional-shifting skills, visuospatial planning and working memory. Participants also received a computerized control test of spatial memory-span. In addition, the interviewer's initial impressions of family members were coded using a new 33-item questionnaire.Results. A significant proportion of parents of autistic ...

Neuroscience Letters, 2005

Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (... more Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (OCD) have generated discrepant results. Here, we genotyped the 5-HTTLPR polymorphism in 106 French OCD patients and 171 healthy controls (case control study). We also performed a family association study on 116 trios including an OCD patient (73 French and 43 German). No association was detected between the 5-HTTLPR polymorphism and OCD in either the case control study or the family study.

NeuroReport, 2004

Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studie... more Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studies have shown a high linkage at chromosome 6q16-21. Among the genes located in this region is the glutamate receptor ionotropic kainate 2 gene (GRIK2 or GLUR6), a functional candidate for susceptibility to schizophrenia. In this study, transmission of GRIK2 was evaluated in 356 schizophrenic patients from three di¡erent clinical centers.Whereas paternal transmission shows equilibrium, we observed maternal transmission disequilibrium of GRIK2 in the largest population (p¼0.03), which was still signi¢cant when all populations were added (p¼0.05). These results are similar to the maternal GRIK2 transmission disequilibrium previously reported for autism, and support the presence of a susceptibility gene for schizophrenia at 6q16.

Genes, Brain and Behavior, 2010

The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the over... more The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the overlap model of bipolar disorder and schizophrenia, we aimed to investigate AKT1 genetic variants and protein expression in both diseases. A total of 679 subjects with European ancestry were included: 384 with schizophrenia, 130 with bipolar disorder and 165 controls. Six single nucleotide polymorphisms (SNPs) were investigated for association with the diseases using single‐ and multi‐locus analyses. AKT1 and AKT2 protein levels were measured in post‐mortem brain tissues from ante‐mortem diagnosed schizophrenia (n = 30) and bipolar disorder subjects (n = 12) and matched controls. The analysis identified a significant global distortion in schizophrenia (P = 0.0026) and a weak association in bipolar disorder (P = 0.046). A sliding window procedure showed a five‐SNP haplotype (TCGAG) to be associated with schizophrenia (P = 1.22 × 10−4) and bipolar disorder (P = 0.0041) and a four‐SNP haplotyp...

European Psychiatry, 2012

BackgroundThe clinical and dimensional features associated with suicidal behaviour in bipolar pat... more BackgroundThe clinical and dimensional features associated with suicidal behaviour in bipolar patients during euthymic states are not well characterised.MethodsIn a sample of 652 euthymic bipolar patients, we assessed clinical features with the Diagnostic Interview for Genetics Studies (DIGS) and dimensional characteristics with questionnaires measuring impulsivity/hostility and affective lability/intensity. Bipolar patients with and without suicidal behaviour were compared for these clinical and dimensional variables.ResultsOf the 652 subjects, 42.9% had experienced at least one suicide attempt. Lifetime history of suicidal behaviour was associated with being a woman, a history of head injury, tobacco misuse and indicators of severity of bipolar disorder including early age at onset, high number of depressive episodes, positive history of rapid cycling, alcohol misuse and social phobia. Indirect hostility and irritability were dimensional characteristics associated with suicidal be...

European Psychiatry, 2002

SummaryProgress in identifying the genetic vulnerability factors in autism requires correct ident... more SummaryProgress in identifying the genetic vulnerability factors in autism requires correct identification of the inherited phenotype(s). This can be achieved not only by the accurate description of the affected subject but also by the identification of vulnerability traits in non-affected relatives of autistic probands. This review will focus on this last strategy and principally on clinical, biochemical and cognitive traits.

Developmental Neuropsychology, 1995

Parents and siblings of 26 autistic females and 26 Down's syndrome females were compared on a... more Parents and siblings of 26 autistic females and 26 Down's syndrome females were compared on a battery of verbal and visuospatial tasks to test the possibility of familial aggregation of a particular cognitive profile. No difference was found between parents of both groups. In contrast, siblings of autistic females showed significantly lower verbal abilities than controls but did not differ in their visuospatial performance. This difference appeared attributable to brothers of autistic females, some of whom showed an especially pronounced discrepant profile at the disadvantage of verbal abilities compared to their visuospatial abilities. Results are discussed in terms of genetic and/or environ mental factors that may account for an aggregation of cognitive features ranging from left‐hemisphere impairments to enhanced right‐hemisphere abilities.

BMC Medical Genetics, 2010

Background: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS... more Background: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. Methods: We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). Results: Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. Conclusions: Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.

Bipolar Disorders, 2008

Objectives: Despite the demonstrated high heritability of bipolar disorder, few susceptibility g... more Objectives: Despite the demonstrated high heritability of bipolar disorder, few susceptibility genes have been identified and linkage and/or association studies have produced conflicting results. This search for susceptibility genes is hampered by several methodological limitations, and environmental risk factors for the disease (requiring incorporation into analyses) remain misunderstood. Among them, childhood trauma is probably the most promising environmental factor for further investigation. The objectives are to review the arguments in favor of an association between childhood trauma and bipolar disorder and to discuss the interpretations of such an observation.Methods: We computed a literature search using PubMed to identify relevant publications concerning childhood trauma and bipolar disorder. We also present some personal data in this field.Results: Growing evidence suggests that incidences of childhood trauma are frequent and severe in bipolar disorder, probably affect ...

Bipolar Disorders, 2009

Background: Normothymic states in bipolar disorders are generally considered to be devoid of sev... more Background: Normothymic states in bipolar disorders are generally considered to be devoid of severe symptoms. However, bipolar patients present subsyndromal symptoms for half of their lives, and often have comorbid psychiatric disorders. If we go beyond the concept of temperamental features, can we identify certain emotional characteristics distinguishing normothymic bipolar patients from normal controls? We previously showed, using self‐completed questionnaires, that normothymic bipolar patients display higher levels of emotional lability and intensity than controls.Objectives: The aim of this study was to assess the emotional reactivity of normothymic bipolar patients, comparing such patients with a normal control group during an experimental mood induction procedure.Method: We evaluated the subjective emotional reactivity of 145 subjects (90 control subjects and 55 normothymic bipolar patients), using an emotional induction method based on the viewing of a set of 18 pictures (...

Schizophrenia Bulletin Open, 2021

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) re... more Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients wa...

The Lancet Psychiatry, 2021

Molecular neurobiology, Sep 25, 2016

Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome... more Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample 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 samples. 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 meta = 5.72 × 10(-4)), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10(-16...

Social Psychiatry and Psychiatric Epidemiology, 2016

Purpose We sought to determine whether significant variation in the incidence of clinically relev... more Purpose We sought to determine whether significant variation in the incidence of clinically relevant psychoses existed at an ecological level in an urban French setting, and to examine possible factors associated with this variation. We aimed to advance the literature by testing this hypothesis in a novel population setting and by comparing a variety of spatial models. Methods We sought to identify all first episode cases of non-affective and affective psychotic disorders presenting in a defined urban catchment area over a 4 years period, over more than half a million person-years at-risk. Because data from geographic close neighbourhoods usually show spatial autocorrelation, we used for our analyses Bayesian modelling. We included small area neighbourhood measures of deprivation, migrants' density and social fragmentation as putative explanatory variables in the models. Results Incidence of broad psychotic disorders shows spatial patterning with the best fit for models that included both strong autocorrelation between neighbouring areas and weak autocorrelation between areas further apart. Affective psychotic disorders showed similar spatial patterning and were associated with the proportion of migrants/foreigners in the area (inverse correlation). In contrast, non-affective psychoses did not show spatial patterning. Conclusions At ecological level, the variation in the number of cases and the factors that influence this variation are different for non-affective and affective psychotic disorders. Important differences in results-compared with previous studies in different settings-point to the importance of the context and the necessity of further studies to understand these differences.

Psychologie Francaise, 1991

The British journal of psychiatry : the journal of mental science, Jan 3, 2015

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses s... more BackgroundBipolar 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.AimsWe 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.MethodTo 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 hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain ...

Frontiers in Bioscience, 2012

Introduction 3. Immuno-inflammatory markers in bipolar disorder 3.1. Abnormalities of the innate ... more Introduction 3. Immuno-inflammatory markers in bipolar disorder 3.1. Abnormalities of the innate and the adaptative system in bipolar disorder 3.2. C-reactive protein (crp) and bipolar disorder 3.3. Autoimmunity in bipolar disorder 3.4. The contribution of immunogenetics in bipolar disorder 4. The viral hypothesis 4.1. A winter/spring excess of birth in bipolar disorder 4.2. Viruses and bipolar disorder 5. The retroviral hypothesis: a new avenue of research? 6.

Psychological Medicine, 2005

Background. Executive dysfunctions in relatives of schizophrenic patients may be trait markers of... more Background. Executive dysfunctions in relatives of schizophrenic patients may be trait markers of genetic liability and thus help us to elucidate the aetiology of schizophrenia. As a large amount of data has been published, a synthesis through a meta-analysis was needed to demonstrate the existence of executive impairments in relatives of schizophrenic patients and to assess their magnitude.Method. We conducted a meta-analysis of articles that compared performances of controls and relatives of schizophrenic patients on the four tests most frequently used to assess executive functions: the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Stroop Test and the Verbal Fluency (VF) Test. When needed and possible, published data were supplemented with information from the authors. After assessing the homogeneity of the data, effect sizes were estimated and publication bias was tested by use of funnel plots.Results. Relatives of schizophrenic patients performed less well...

Psychological Medicine, 1997

Background. Previous studies have shown that individuals with autism show impaired performance on... more Background. Previous studies have shown that individuals with autism show impaired performance on tests of executive function (Ozonoff et al. 1991, 1993; Hughes & Russell, 1993; Hughes et al. 1994). There is also strong evidence for genetic involvement in autism (see Rutter, 1991 for review). If executive dysfunction is a core impairment in autism, then similar impairments are hypothesized to exist in a subtler form among the parents of autistic children.Methods. Forty parents of autistic children were compared with 40 parents of learning disabled children and 36 adults from unaffected families on three computerized tests of executive function. These tasks tapped attentional-shifting skills, visuospatial planning and working memory. Participants also received a computerized control test of spatial memory-span. In addition, the interviewer's initial impressions of family members were coded using a new 33-item questionnaire.Results. A significant proportion of parents of autistic ...

Neuroscience Letters, 2005

Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (... more Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (OCD) have generated discrepant results. Here, we genotyped the 5-HTTLPR polymorphism in 106 French OCD patients and 171 healthy controls (case control study). We also performed a family association study on 116 trios including an OCD patient (73 French and 43 German). No association was detected between the 5-HTTLPR polymorphism and OCD in either the case control study or the family study.

NeuroReport, 2004

Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studie... more Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studies have shown a high linkage at chromosome 6q16-21. Among the genes located in this region is the glutamate receptor ionotropic kainate 2 gene (GRIK2 or GLUR6), a functional candidate for susceptibility to schizophrenia. In this study, transmission of GRIK2 was evaluated in 356 schizophrenic patients from three di¡erent clinical centers.Whereas paternal transmission shows equilibrium, we observed maternal transmission disequilibrium of GRIK2 in the largest population (p¼0.03), which was still signi¢cant when all populations were added (p¼0.05). These results are similar to the maternal GRIK2 transmission disequilibrium previously reported for autism, and support the presence of a susceptibility gene for schizophrenia at 6q16.

Genes, Brain and Behavior, 2010

The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the over... more The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the overlap model of bipolar disorder and schizophrenia, we aimed to investigate AKT1 genetic variants and protein expression in both diseases. A total of 679 subjects with European ancestry were included: 384 with schizophrenia, 130 with bipolar disorder and 165 controls. Six single nucleotide polymorphisms (SNPs) were investigated for association with the diseases using single‐ and multi‐locus analyses. AKT1 and AKT2 protein levels were measured in post‐mortem brain tissues from ante‐mortem diagnosed schizophrenia (n = 30) and bipolar disorder subjects (n = 12) and matched controls. The analysis identified a significant global distortion in schizophrenia (P = 0.0026) and a weak association in bipolar disorder (P = 0.046). A sliding window procedure showed a five‐SNP haplotype (TCGAG) to be associated with schizophrenia (P = 1.22 × 10−4) and bipolar disorder (P = 0.0041) and a four‐SNP haplotyp...

European Psychiatry, 2012

BackgroundThe clinical and dimensional features associated with suicidal behaviour in bipolar pat... more BackgroundThe clinical and dimensional features associated with suicidal behaviour in bipolar patients during euthymic states are not well characterised.MethodsIn a sample of 652 euthymic bipolar patients, we assessed clinical features with the Diagnostic Interview for Genetics Studies (DIGS) and dimensional characteristics with questionnaires measuring impulsivity/hostility and affective lability/intensity. Bipolar patients with and without suicidal behaviour were compared for these clinical and dimensional variables.ResultsOf the 652 subjects, 42.9% had experienced at least one suicide attempt. Lifetime history of suicidal behaviour was associated with being a woman, a history of head injury, tobacco misuse and indicators of severity of bipolar disorder including early age at onset, high number of depressive episodes, positive history of rapid cycling, alcohol misuse and social phobia. Indirect hostility and irritability were dimensional characteristics associated with suicidal be...

European Psychiatry, 2002

SummaryProgress in identifying the genetic vulnerability factors in autism requires correct ident... more SummaryProgress in identifying the genetic vulnerability factors in autism requires correct identification of the inherited phenotype(s). This can be achieved not only by the accurate description of the affected subject but also by the identification of vulnerability traits in non-affected relatives of autistic probands. This review will focus on this last strategy and principally on clinical, biochemical and cognitive traits.

Developmental Neuropsychology, 1995

Parents and siblings of 26 autistic females and 26 Down's syndrome females were compared on a... more Parents and siblings of 26 autistic females and 26 Down's syndrome females were compared on a battery of verbal and visuospatial tasks to test the possibility of familial aggregation of a particular cognitive profile. No difference was found between parents of both groups. In contrast, siblings of autistic females showed significantly lower verbal abilities than controls but did not differ in their visuospatial performance. This difference appeared attributable to brothers of autistic females, some of whom showed an especially pronounced discrepant profile at the disadvantage of verbal abilities compared to their visuospatial abilities. Results are discussed in terms of genetic and/or environ mental factors that may account for an aggregation of cognitive features ranging from left‐hemisphere impairments to enhanced right‐hemisphere abilities.

BMC Medical Genetics, 2010

Background: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS... more Background: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. Methods: We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). Results: Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. Conclusions: Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.

Bipolar Disorders, 2008

Objectives: Despite the demonstrated high heritability of bipolar disorder, few susceptibility g... more Objectives: Despite the demonstrated high heritability of bipolar disorder, few susceptibility genes have been identified and linkage and/or association studies have produced conflicting results. This search for susceptibility genes is hampered by several methodological limitations, and environmental risk factors for the disease (requiring incorporation into analyses) remain misunderstood. Among them, childhood trauma is probably the most promising environmental factor for further investigation. The objectives are to review the arguments in favor of an association between childhood trauma and bipolar disorder and to discuss the interpretations of such an observation.Methods: We computed a literature search using PubMed to identify relevant publications concerning childhood trauma and bipolar disorder. We also present some personal data in this field.Results: Growing evidence suggests that incidences of childhood trauma are frequent and severe in bipolar disorder, probably affect ...

Bipolar Disorders, 2009

Background: Normothymic states in bipolar disorders are generally considered to be devoid of sev... more Background: Normothymic states in bipolar disorders are generally considered to be devoid of severe symptoms. However, bipolar patients present subsyndromal symptoms for half of their lives, and often have comorbid psychiatric disorders. If we go beyond the concept of temperamental features, can we identify certain emotional characteristics distinguishing normothymic bipolar patients from normal controls? We previously showed, using self‐completed questionnaires, that normothymic bipolar patients display higher levels of emotional lability and intensity than controls.Objectives: The aim of this study was to assess the emotional reactivity of normothymic bipolar patients, comparing such patients with a normal control group during an experimental mood induction procedure.Method: We evaluated the subjective emotional reactivity of 145 subjects (90 control subjects and 55 normothymic bipolar patients), using an emotional induction method based on the viewing of a set of 18 pictures (...

European Neuropsychopharmacology, 2017

As part of the ROAMER project, we aimed at revealing the share of health research budgets dedicat... more As part of the ROAMER project, we aimed at revealing the share of health research budgets dedicated to mental health, as well as on the amounts allocated to such research for four European countries. Finland, France, Spain and the United Kingdom national public and non-profit funding allocated to mental health research in 2011 were investigated using, when possible, bottom-up approaches. Specifics of the data collection varied from country to country. The total amount of public and private not for profit mental health research funding for Finland, France, Spain and the UK was €10 Á 2, €84 Á 8, €16 Á 8, and €127 Á 6 million, respectively. Charities accounted for a quarter of the funding in the UK and less than six per cent elsewhere. The share of health research dedicated to mental health ranged from 4 Á 0% in the UK to 9 Á 7% in Finland. When compared to the DALY attributable to mental disorders, Spain, France, Finland, and the UK invested respectively €12 Á 5, €31 Á 2, €39 Á 5, and €48 Á 7 per DALY. Among these European countries, there is an important gap between the level of mental health research funding and the economic and epidemiologic burden of mental disorders.