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Marion Leboyer

Publications and source records attributed to Marion Leboyer.

52 records · Page 3Linked to original sources
PubMed2003

Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family-based association study of 55 trios. Extended transmission-disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene (P = 0.005). Moreover, in a population-based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically-matched controls (P = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family- and population-based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms.

Adolescent↗
PubMed2003

Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states.

BACKGROUND: The relationship between depression and mania remains poorly understood and is responsible for much of the confusion about mixed states. The difficulty in conceptualizing opposite states such as euphoric and depressive moods during the same episode may account for the considerable differences in reported frequencies of mixed states, among acutely manic patients. It is possible that the fundamental mood characteristic of mania is not tonality of mood (e.g. euphoric, irritable or depressed mood), but rather the intensity of emotions. METHOD: We interviewed 30 patients hospitalized for a manic episode, asking about their symptoms during the episode, using the list of symptoms for manic and depressive episode of the DSM-IV criteria. Emotional hyper-reactivity, defined as an increase in the intensity of all emotions, was assessed using the Hardy Scale. Manic symptoms were also assessed by a clinician using the Beck-Rafaelsen Mania Scale. RESULTS: This study showed that most of the manic episodes presented many dysphoric symptoms, more particularly depressive mood (33%), irritability (53%), anxiety (76%), and recurrent thoughts of death or suicidal ideation (33%). However, only 10% of our sample met the criteria for mixed state. The other symptoms reported by patients and included in the DSM-IV criteria for depressive mood are common between depressive and manic episodes. All patients (100%) reported that they felt all their emotions with an unusual intensity. CONCLUSION: We suggest that the most appropriate way to define mood in manic states is as a function of intensity, and not as a function of tonality. This definition circumvents the arbitrary dichotomy between mania and mixed state. With this definition, manic episodes can be described as being more or less dysphoric, with the actual characteristics of dysphoria encompassing irritability, anxiety, or depressive affect. This point could be extremely helpful in discriminating mixed state or dysphoric mania from depression.

Adult↗
PubMed2003

[Genetics of autism: from genome scans to candidate genes].

The autistic disorder was firstly described by Leo Kanner sixty years ago. This complex developmental disability is characterized by social and communicative impairments and repetitive and stereotyped behaviours and interests. The prevalence of autism in the general population is about 1 in 1,000, with four males affected for one female. In approximately 15% of the cases, autism is associated with known genetic disorders, such as fragile X syndrome, tuberous sclerosis or Rett syndrome. Nevertheless, a recognised medical etiology can only be identified in a minority of cases. A higher recurrence risk in families with autistic subjects (45 times greater than the prevalence in the general population) and higher concordance for autism among monozygotic (60-90%) than dizygotic (0-10%) twins argue for a genetic predisposition to idiopathic autism. The past decade has been marked by an increased interest in the genetic basis of autism, with a series of multiple independent whole genome scans and chromosomal abnormalities studies. These analyses have pointed out several candidate regions on chromosomes 2q, 7q, 6q, 15q and sex chromosomes. These regions possess candidate genes that have been screened for mutations or association with autism. However, a clear involvement of a major susceptibility gene (or genes) in autism remains far from clear. The results from linkage studies and the clear drop in the concordance rates between monozygotic and dizygotic twins suggests that the genetic aetiology of autism is certainly heterogeneous (different genes in different families) and polygenic (more than one affected gene per individual). The almost finished sequence of the human genome and the generation of haplotype maps will shed light on the inter-individual genetic variability and will certainly increase the power and reliability of association studies for complex traits, such as autism.

Autistic Disorder↗
PubMed2003

Age at onset in bipolar I affective disorder: further evidence for three subgroups.

OBJECTIVE: Preliminary data suggested that there are three subgroups of bipolar affective disorder based on age at onset. The authors sought to replicate those findings and determine the cut-off age of each subgroup. METHOD: Admixture analysis was used to determine the best-fitting model for the observed ages at onset of 368 consecutively admitted patients. The results obtained were compared with those of the previously described model. The authors also investigated whether affected siblings are more likely to belong to the same theoretical age-at-onset subgroup as identified by admixture analysis. RESULTS: The existence of three subgroups defined by age at onset was confirmed. The mean ages estimated in this model were 17.4 years (SD=2.3), 25.1 years (SD=6.2), and 40.4 years (SD=11.3). Affected siblings were more likely to belong to the same theoretical subgroup. CONCLUSIONS: There are three age-at-onset subgroups of bipolar patients, and specific familial vulnerability factors might underlie each subgroup.

Adolescent↗
PubMed2003

Familial aggregation of delusional proneness in schizophrenia and bipolar pedigrees.

OBJECTIVE: Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands. METHOD: The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives. RESULTS: Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands. CONCLUSIONS: Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies.

Adult↗
PubMed2003

Anxiety disorders in 318 bipolar patients: prevalence and impact on illness severity and response to mood stabilizer.

OBJECTIVE: The aim of this study was to assess the frequency and impact of anxiety disorders on illness severity and response to mood stabilizers in bipolar disorders. METHOD: 318 bipolar patients consecutively admitted to the psychiatric wards of 2 centers as inpatients were recruited. Patients were interviewed with a French version of the Diagnostic Interview for Genetic Studies providing DSM-IV Axis I diagnoses and demographic and historical illness characteristics. Logistic and linear regressions to adjust for age and sex were performed. RESULTS: In a population with mostly bipolar type I patients (75%), 24% had at least 1 lifetime anxiety disorder (47% of these patients had more than 1 such disorder), 16% of patients had panic disorder (with and without agoraphobia, and panic attacks), 11% had phobia (agoraphobia without panic disorder, social phobia, and other specific phobias), and 3% had obsessive-compulsive disorder. Comorbidity with anxiety disorders was not correlated with severity of bipolar illness as assessed by the number of hospitalizations, psychotic characteristics, misuse of alcohol and drugs, and suicide attempts (violent and nonviolent). Bipolar patients with an early onset of illness had more comorbidity with panic disorder (p <.05). Anxiety disorders were detected more frequently in bipolar II patients than in other patients, but this difference was not significant (p =.09). Bipolar patients with anxiety responded less well to anticonvulsant drugs than did bipolar subjects without anxiety disorder (p <.05), whereas the efficacy of lithium was similar in the 2 groups. There was also a strong correlation between comorbid anxiety disorders and depressive temperament in bipolar patients (p =.004). CONCLUSION: Patients with bipolar disorders often have comorbid anxiety disorders, particularly patients with depressive temperament, and the level of comorbidity seems to decrease the response to anticonvulsant drugs.

Adult↗
PubMed2002

Serotonin transporter gene polymorphism influences age at onset in patients with bipolar affective disorder.

Serotonin transporter (SLC6A4) gene polymorphism is associated with several behavioral and psychiatric traits. In bipolar affective disorder, two polymorphisms of the SLC6A4 gene, a variable number of tandem repeats in the second intron and a 44 bp insertion/deletion in the serotonin transporter gene linked polymorphic region (5-HTTLPR), have been extensively studied. The findings are conflicting possibly because of the heterogeneity of bipolar disorder. Early-onset bipolar disorder appears to be clinically and genetically more homogeneous and was recently suggested to be associated with the 5-HTTLPR polymorphism. We tested the association between two polymorphisms of the SLC6A4 gene and age at onset (AAO) in a sample of bipolar patients. For both SLC6A4 gene polymorphisms, AAO of subjects with different genotypes were compared. SLC6A4 genotype distributions of different AAO groups were also compared. The variable number of tandem repeats (VNTR) polymorphism significantly influences the AAO but the serotonin transporter gene linked polymorphic region (5-HTTLPR) polymorphism did not. Patients carrying at least one VNTR STin2.12 allele began their illness later whereas patients carrying the 'ss' genotype tended to begin their illness earlier. Differential sampling procedures may influence the proportion of AAO subgroups in a given association study, and therefore these results may explain the conflicting results obtained in studies of the association between the SLC6A4 gene polymorphism and bipolar affective disorder (BPAD).

Adolescent↗
PubMed2002

Investigation of two variants in the DOPA decarboxylase gene in patients with autism.

Though genetic risk factors are important for the development of autism, no specific risk alleles have yet been identified. DOPA decarboxylase (DDC) is involved in both the catecholaminergic and serotonergic pathways and may be considered a functional candidate gene for autism. The present study is the first to test if two new variants of possible functional significance in the DDC gene increase the susceptibility to autism. A total of 90 parent-offspring trios recruited in Denmark and France were investigated using the transmission disequilibrium test (TDT). We found no evidence of linkage disequilibrium between autism and either of the two polymorphisms. Nor did we find linkage disequilibrium between autism and haplotypes of the two variants using a multiallelic TDT. These findings suggest that the DDC gene is unlikely to play a major role in the development of autism in our data set.

Adolescent↗
PubMed2002

Analysis of ten candidate genes in autism by association and linkage.

We studied the possible involvement of ten candidate genes in autism: proenkephalin, prodynorphin, and proprotein convertase subtilisin/kexin type 2 (opioid metabolism); tyrosine hydroxylase, dopamine receptors D2 and D5, monoamine oxidases A and B (monoaminergic system); brain-derived neurotrophic factor, and neural cell adhesion molecule (involved in neurodevelopment). Thirty-eight families with two affected siblings and one family with two affected half-siblings, recruited by the Paris Autism Research International Sibpair Study (PARIS), were tested using the transmission disequilibrium test and two-point affected sib-pair linkage analysis. We found no evidence for association or linkage with intragenic or linked markers. Our family sample has good power for detecting a linkage disequilibrium of 0.80. Thus, these genes are unlikely to play a major role in the families studied, but further studies in a much larger sample would be needed to highlight weaker genetic effects.

Alleles↗
PubMed2002

Association between the COMT locus and obsessive-compulsive disorder in females but not males.

A polymorphism in the coding region of catechol-O-methyltransferase gene (COMT) was previously reported to be associated with obsessive-compulsive disorder (OCD), particularly in male probands. We attempted to replicate the previous finding using a family-based genetic design in haplotype relative risk (HRR) and transmission disequilibrium (TDT) analyses. Fifty-six OCD probands and their parents were genotyped for the COMT locus using established methods. Analysis of allele and genotype frequencies between the proband genotypes and the control (parental nontransmitted) genotypes failed to replicate the previous finding of gender divergence, gave no evidence of overall association, nor was linkage detected by TDT. However, further analysis of the COMT allele frequencies by proband gender gave evidence of a mildly significant association with the low-activity COMT allele in female probands (P=0.049), but not in male probands. These findings indicate that COMT may be etiologically relevant to OCD in a gender-specific manner opposite to that shown in previous studies.

Adolescent↗
PubMed2002

Mid-morning tryptophan depletion delays REM sleep onset in healthy subjects.

Because serotonin is involved in the diachronic regulation of sleep, we tested the effect of a midmorning rapid deficiency in the serotonin precursor tryptophan on the next night's sleep. After a 48-h low-protein diet, 17 healthy volunteers received either a tryptophan-free mixture of amino acids or a placebo at 10:30 A.M., in a randomized double-blind cross-over design, resulting in a 77% decrease and 41% decrease of serum tryptophan at 3:30 P.M. and 9:30 P.M., respectively. Urinary sulfatoxy-melatonin excretion and mood were unaffected by the rapid tryptophan depletion (RTD), but rapid eye movement (REM) sleep latency increased by 21 min (from 91.5 +/- 4.5 min to 112.2 +/- 6.9 min), sleep fragmentation 58%, and REM density of the first REM sleep period doubled. The results show that midmorning RTD delays REM sleep latency during following night-time sleep, whereas evening RTD shortens REM sleep latency in previous studies, and suggest that the serotonin control of REM sleep latency is upregulated.

Adolescent↗
PubMed2002

Fringe phenotypes in autism: a review of clinical, biochemical and cognitive studies.

Progress 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.

Autistic Disorder↗
PubMed2002

Temperament in schizophrenia: a study of the tridimensional personality questionnaire (TPQ).

PURPOSE: The aim of this study was to assess dimensions of temperament as defined by Cloninger's neurobiological model using the tridimensional personality questionnaire (TPQ) in a sample of consecutively recruited schizophrenic patients. SUBJECTS AND METHODS: We used the French version of the TPQ to compare 45 stable, euthymic schizophrenic patients with 126 controls with no personal or familial history of psychiatric disorder. After comparison of TPQ scores between groups, we also performed a multivariate analysis to avoid the confounding effects of age, gender, and alcohol and substance use disorder comorbidity. RESULTS: Harm avoidance (HA) was higher in schizophrenic patients than in controls. DISCUSSION AND CONCLUSION: This replicates and extends the results of previous studies suggesting that schizophrenic patients have high HA and that HA might be a marker for underlying genetic vulnerability to schizophrenia.

Adult↗