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F Bellivier

Publications and source records attributed to F Bellivier.

At least 19 recordsLinked to original sources
PubMed2006

Lack of influence of COMT and NET genes variants on executive functions in schizophrenic and bipolar patients, their first-degree relatives and controls.

Abnormal dopaminergic function in the prefrontal cortex (PFC) may be a key factor in the etiopathogeny of schizophrenia and bipolar disorder. Both schizophrenic and bipolar subjects have executive functions (EF) deficits, thought to reflect abnormal PFC function. The main inactivation pathways for dopamine in the PFC are enzymatic cleavage by the Carboxy-O-Methyl-Transferase (COMT) and reuptake by the nor-epinephrine transporter (NET). Our aim in this study was to replicate previous studies that investigated influence of the COMT genotype on EF in schizophrenic subjects, their relatives and controls and extend their scope by including bipolar patients, and their relatives and by exploring NET gene polymorphisms influence on executive performances. We investigated one functional polymorphism of the COMT gene and two polymorphisms of the NET gene. EF were assessed by means of the Trail Making Test (TMT) and the Wisconsin Card Sorting Test (WCST). We assessed the effect of each of the three genotypes on EF for the whole sample (N = 318) and separately in schizophrenic (N = 66), bipolar (N = 94) and healthy subjects (i.e., relatives and controls N = 158). Separate analyses were performed because of the presence, in patients samples, of potentially confounding factors, especially medication. Genotype had no significant effect on the cognitive measures in any of the analyses (for the two EF measures, the three polymorphisms, and the four groups). In our sample we found no evidence in favor of a major effect of COMT or NET polymorphisms on the two tests of EF.

Adult↗
PubMed2006

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non-parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (AAO of 21 years or below). Non-parametric multipoint analysis suggested eight regions of linkage with P-values<0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide P-value estimated over 10 000 simulated replicates of 0.015 [0.01-0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.

Adolescent↗
PubMed2005

Schizophrenia, antipsychotics and diabetes: Genetic aspects.

The relatively high comorbidity of type 2 diabetes and schizophrenia may suggest a shared biological susceptibility to these two conditions. Family studies have demonstrated an increased risk of diabetes in unaffected relatives of patients with schizophrenia, consistent with a heritable susceptibility trait. Linkage analyses have identified several loci that are associated with schizophrenia and some of these, notably those on chromosomes 2p22.1-p13.2 and 6g21-824.1 have also been observed in linkage studies in type 2 diabetes. In addition, the dopamine D5 receptor on chromosome 5 and the tyrosine hydroxylase gene on chromosome 11 have both been suggested as candidate genes in schizophrenia and may also be implicated in susceptibility to poor glycaemic control. In addition, an increased rate of type II diabetes has been observed in some patients treated with antipsychotics. Potential neurochemical substrates of this effect include the histamine H1 receptor, the 5-HT2C serotonin receptor or the beta3 adrenoreceptor. However, the search for a genetic basis to the association between diabetes and schizophrenia is still in its infancy, and much further work needs to be performed, including the systematic screening of all confirmed susceptibility loci and quantitative trait locus mapping of glycaemic control.

Chromosomes, Human, Pair 11↗
PubMed2003

Antidepressant-induced mania, rapid cycling and the serotonin transporter gene polymorphism.

The genes involved in the serotonin system are major candidates in association studies on affective disorders and responses to antidepressants. We studied a functional polymorphism of the serotonin transporter (5-HTT) gene (a 44 bp insertion/deletion in the 5-HTT-linked polymorphic region (5-HTTLPR)) and lifetime history of antidepressant-induced mania (AIM) in a population of 305 patients with bipolar affective disorder. AIM was defined using a broad definition and a restrictive definition. No association was found between the "s" allele of the 5-HTTLPR and AIM for either definition. However, we found an association between the 5-HTTLPR and lifetime history of rapid cycling in a subsample of patients (for allele and genotype distributions: exact probability, p=0.0009 and chi(2)=9.4; df=1; p=0.002, respectively). These results may help to explain the conflicting association results obtained with the 5-HTT gene polymorphism, in particular with AIM. Indeed, the precise phenotype associated with the 5-HTT gene is unclear. The association between the "s" allele and rapid cycling may provide further evidence for an association between the 5-HTTLPR "s" allele and a pattern of affective instability.

Adult↗
PubMed2001

Serotonin transporter gene polymorphism and psychiatric disorders in NF1 patients.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease characterized by a broad clinical expression. Comorbid affective disorders, anxiety disorders, and suicide are frequently observed during NF1. The promoter marker (5-HTTLPR) of the serotonin transporter gene (5-HTT) has been shown to be associated with major affective disorders, anxiety-related trait, and more recently with suicidal behavior. This gene is adjacent to the NF1 gene, raising the question of the implication of the 5-HTT gene in the psychiatric comorbidity during NF1. Eighty-eight patients with NF1 and 184 screened controls were typed for the 5-HTTLPR. No deviation from the Hardy-Weinberg equilibrium in patients was observed. In addition, allele and genotype frequencies were similar in the two groups. Our data do not support the implication of the 5-HTT gene in the psychiatric comorbidities of NF1.

Alleles↗
PubMed2001

Bipolar sensation seeking is associated with a propensity to abuse rather than to temperamental characteristics.

OBJECTIVE: As some temperament profiles may be markers of genetic vulnerability traits, we aimed to compare sensation seeking in euthymic bipolar patients and in controls. METHODS: One hundred ninety-four patients fulfilling DSM-IV diagnostic criteria for bipolar disorders (BP), 81% of whom presented type I BP, and 95 controls were included in this study. Euthymia was assessed using both the MADRS and Bech mania scales. Subjects were evaluated using the French abbreviated form of Zuckerman's Sensation Seeking Scale (SSS), which provide a total score (TS) and four subscores: Thrill and Adventure Seeking (TAS), Experience Seeking (ES), Disinhibition (Dis), and Boredom Susceptibility (BS). RESULTS: SSS total score differed significantly between men (17.2 +/- 0.5) and women (15.3 +/- 0.6) (P = 0.02) and all the subscores were negatively correlated with age. On adjustment for sex and age, we found that bipolar patients had a high Dis score (P = 0.003). However, if the same analysis was performed with a lifetime history of alcohol abuse or dependence as a covariable, no such difference was found (P = 0.436). The SSS demonstrated a high degree of test-retest reliability (ICC = 0.91). CONCLUSION: These results suggest that sensation seeking assessed with the SSS is not a temperament characteristic associated with bipolar disorders but is instead linked to a tendency towards alcohol abuse.

Adult↗
PubMed2001

Suicide attempts and the tryptophan hydroxylase gene.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.

Adult↗
PubMed2000

Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders.

BACKGROUND: Genes involved in the serotonin system are major candidates in association studies of suicidal behavior. In this case-control study we investigated whether the serotonin transporter (5-HTT) gene encoding the protein responsible for the reuptake of serotonin from the synapse after its release from serotonergic neurons is a susceptibility factor for suicidal behavior. METHODS: A functional polymorphism of the 5-HTT gene (a 44-base pair insertion/deletion in the 5-HTT-linked polymorphic region [5-HTTLPR]) was studied in a population of 237 consecutive patients with affective disorder (unipolar or bipolar) and 187 control subjects. Ninety-nine patients had attempted suicide at least once, of whom 26 made a violent attempt. RESULTS: No association was found between the "s" allele of the 5-HTTLPR and suicide attempt; however, there was a significant difference in allele distributions between patients who had made violent suicide attempts and control subjects. CONCLUSIONS: A genetic variant of the 5-HTT gene may predispose individuals to violent suicidal behavior. The precise phenotype associated with the 5-HTT gene is unclear, and therefore further studies are required to replicate these findings.

Adult↗
PubMed2000

Early and late onset bipolar disorders: two different forms of manic-depressive illness?

BACKGROUND: Conflicting results in genetic studies of bipolar disorders may be due to the clinical and genetic heterogeneity of the disease. Age at onset of bipolar disorders may be a key indicator for identifying more homogeneous clinical subtypes. We tested whether early onset and late onset bipolar illness represent two different forms of bipolar illness in terms of clinical features, comorbidity and familial risk. METHODS: Among a consecutively recruited sample of 210 bipolar patients, we compared early onset (n=58) and late onset (n=39) bipolar patients; the cut-off points were age at onset before 18 years and after 40 years for the two subgroups. The subgroups were compared by independent t tests and a contingency table by raw chi-square test. Morbid risk among first-degree relatives was measured by the survival analysis method. RESULTS: The early onset group had the most severe form of bipolar disorder with more psychotic features (P=0.03), more mixed episodes (P=0.01), greater comorbidity with panic disorder (P=0.01) and poorer prophylactic lithium response (P=0.04). First degree relatives of early onset patients also had a higher risk of affective disorders (P=0.0002), and exhibit the more severe phenotype, i.e bipolar disorder. CONCLUSION: Our data suggest that early and late onset bipolar disorders differ in clinical expression and familial risk and may therefore be considered to be different subforms of manic-depressive illness.

Adolescent↗
PubMed2000

The DRD2 gene and the risk for alcohol dependence in bipolar patients.

The high co-morbidity between bipolar disorder and alcohol dependence may have different explanations, one of them being the existence of common genetic factors for the two disorders. Several candidate genes may be involved but the genes acting in the dopaminergic pathway may be more specifically involved. We have thus tested the role of the gene encoding the D2 dopamine receptor (TaqI A1 allele) in the potentially shared vulnerability to alcohol dependence and bipolar disorder. One hundred and twenty-two French (for at least two generations) patients were recruited on the basis of hospital or outpatient files and were interviewed with the DIGS. The A1 allele frequencies were compared between four groups, namely, with bipolar patients and co-morbid alcohol dependence (N = 21), with bipolar patients without alcohol morbidity (N = 31), with alcohol dependence without mood disorder (N = 35) and unaffected controls (N = 35). The Hardy Weinberg equilibrium for the DRD2 Taq1 A1 genotypes was respected for the sample as a whole, and for each subsample. We observed that 42.9% of control subjects have at least one A1 allele, a frequency which is not significantly different from the one observed in the affected sample as a whole (39.1%), neither from patients with alcohol dependence (37.1%), patients with bipolar disorder (48.4%) nor patients with alcohol dependence and bipolar disorder (28.6%). The regression analysis based on the three variables (bipolar disorder, alcohol dependence and interaction between these two disorders) does not explain the presence of the A1 allele of the DRD2 gene. We thus found no evidence for a significant role of the A1 allele of the D2 dopamine receptor gene in the specific association between bipolar disorder and alcohol dependence in our sample.

Adult↗
PubMed2000

Association between bipolar disorder and monoamine oxidase A gene polymorphisms: results of a multicenter study.

OBJECTIVE: Although genetic factors have been implicated in the etiology of bipolar disorder, no specific gene has been conclusively identified. Given the link between abnormalities in serotonergic neurotransmission and bipolar disorder, a candidate gene association approach was applied to study the involvement of the monoamine oxidase A (MAOA) gene, which codes for a catabolic enzyme of serotonin, in the susceptibility to bipolar disorder. METHOD: In France and Switzerland, 272 patients with bipolar disorder and 122 healthy subjects were typed for three polymorphic markers of the MAOA gene: the MAOA-CA repeat, the MAOA restriction fragment length polymorphism (RFLP), and a repeat directly adjacent to the variable number of tandem repeats (VNTR) locus. RESULTS: A significant difference in the distribution of the alleles for the MAOA-CA repeat was observed between the female bipolar patients and comparison group. CONCLUSIONS: The results obtained in the French and Swiss population confirm findings from two studies conducted in the United Kingdom.

Adult↗
PubMed1999

Temperament in bipolar illness: impact on prognosis.

OBJECTIVE: The present study was designed to investigate the relations between temperament and outcome in bipolar illness. METHODS: Seventy-two patients presenting with bipolar type I disorder were recruited from consecutive admissions and evaluated when euthymic. The criteria developed by Akiskal and Mallya (Criteria for the 'soft' bipolar spectrum: treatment implications. Psychopharmacol. Bull. 1987;23:68-73) were used to assess both depressive (DT) and hyperthymic temperaments (HT) in a dimensional approach. RESULTS: Multiple regression analysis showed that a higher DT score or a lower HT score were significantly associated with a greater number of episodes. Furthermore, a higher DT score was strongly associated with a higher percentage of major depressive episodes. Conversely, a higher HT score was associated with a trend to manic rather than depressive episodes. Suicide attempts appeared more frequent in the history of patients presenting with higher DT scores. CONCLUSIONS: Our findings strengthen the hypothesis that temperament is one of the main variables accounting for some features in the clinical evolution of bipolar disorder such as polarity of episodes. Furthermore, these findings are consistent with the hypothesis of a trait-state continuum between personality and affective episodes.

Adult↗
PubMed1998

Age at onset and gender resemblance in bipolar siblings.

In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific.

Adolescent↗
PubMed1998

Serotonin transporter gene polymorphisms in patients with unipolar or bipolar depression.

To explore the involvement of serotonin transporter (5HTT) in mood disorder, we studied two polymorphisms of the 5HTT gene (a variable number of tandem repeats in the second intron (VNTR) and a 44 bp insertion/deletion in the 5HTT linked polymorphic region (5-HTTLPR)) in a sample of unipolar and bipolar patients and controls. Homozygosity for the short variant of the 5-HTTLPR was significantly more frequent in bipolar patients than in controls (chi2 = 4.68, d.f. = 1, P = 0.03) whereas there was no difference between bipolar patients and controls for allele distribution, suggesting a recessive effect. The interaction between the two markers suggests that the two polymorphisms probably have independent effects to determine the susceptibility to affective disorder. Further studies are required to identify the precise phenotype associated with 5HTT polymorphisms in depressed patients.

Adult↗
PubMed1998

CAG repeat sequences in bipolar affective disorder: no evidence for association in a French population.

Anticipation has been described in bipolar affective disorder (BPAD). However, there are conflicting results from association studies screening for a link between BPAD and CAG/CTG repeat expansions, the molecular basis of anticipation in several hereditary neurodegenerative disorders. Here, the repeat expansion detection (RED) method was used to screen for CAG repeat expansion in 119 French BPAD patients. Western blotting was also used to search for polyglutamine stretches, encoded by CAG expansion, among proteins, extracted from lymphoblastoid cell lines, from six selected familial cases. Maximum CAG/CTG repeat length did not differ significantly (P = 0.38) between the 119 BPAD patients and the 88 controls included in the study. Several categories of subgroups were used, none of which showed significant association with a long repeat. Nor was a specific protein with an unusually long polyglutamine stretch (lower detection limit, approximately 33 polyglutamines) detected in cell lysates from the familial cases studied. In conclusion, an association between a long CAG/CTG repeat and BPAD in the French population sample studied was not found. Nonetheless, a short repeat (<40 repeats) might still be implicated, and this possibility warrants further study.

Adult↗