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Frank Bellivier

Publications and source records attributed to Frank Bellivier.

At least 19 recordsLinked to original sources
PubMed2007

The influence of four serotonin-related genes on decision-making in suicide attempters.

Genetic factors have been associated with the vulnerability to suicidal behavior. We previously reported decision-making impairment in suicide attempters and hypothesized that these cognitive alterations may represent an endophenotype of suicidal behavior. In this study, we aimed to investigate the influence of four serotonin-related genes relevant to suicidal behavior on decision-making, in a large population of suicide attempters. The Iowa Gambling Task was used to assess decision-making in 168 patients with a personal history of attempted suicide. Patients were genotyped for four serotonergic polymorphisms: 5HTTLPR, TPH1 A218C, MAOA u-VNTR, and TPH2 rs1118997. Patients carrying the 5HTTLPR-ll and -sl, TPH1-CC and -AC, MAOA-HH (in women) and TPH2-AA genotypes significantly improved their performance during the task, suggesting a genetic modulation of the learning process required for advantageous decision-making. In contrast, genotypes previously associated with a higher risk of suicidal behavior, a greater sensitivity to the environment and a higher propensity to negative feelings are those conferring poorer learning abilities. We hypothesize that the influence of genetic factors on the vulnerability to suicidal behavior may partly be achieved through their modulation of decision-making and particularly its learning component.

Adolescent↗
PubMed2007

Schizotypal dimensions: an intermediate phenotype associated with the COMT high activity allele.

BACKGROUND: Although catechol-O-methyltransferase (COMT) has long been suggested to be implicated in the pathogenesis of schizophrenia, association studies have generated discrepant results concerning the involvement of the COMT gene in schizophrenia. As several studies have suggested that schizotypal traits might be genetically related to schizophrenia, increased statistical power to detect gene effects could be obtained by using dimensional personality traits in unaffected relatives. METHODS: We tested the hypothesis that the functional Val158Met COMT polymorphism might contribute to the variance of self-reported schizotypal scores in a sample of 106 unaffected subjects, composed of controls (N = 57), first-degree relatives of schizophrenic (N = 27) and of bipolar (N = 22) probands. We also looked for specific associations between COMT polymorphisms and the three dimensions of schizotypy (positive, negative, disorganized) assessed by the Schizotypal Personality Questionnaire (SPQ). RESULTS: We found that self-reported SPQ scores are related to COMT genotype (P = 0.01), with individuals homozygous for the high activity allele having the highest scores. This association is primarily due to specific associations with the positive (P = 0.001) and negative (P = 0.04) dimensions. CONCLUSIONS: Our data support the hypothesis that the functional COMT polymorphism could be involved in different psychotic dimensions. This confirms that studying specific schizotypal dimensions can help to identify the genes involved in the pathogenesis of psychosis.

Adult↗
PubMed2006

Prefrontal cortex dysfunction in patients with suicidal behavior.

BACKGROUND: Abnormal serotonergic neurotransmission has long been demonstrated in suicidal behavior. The dorsal and median raphe nuclei housing the main serotonergic cell bodies and the prefrontal cortex (PFC), particularly the ventral part innervated by the serotonergic system, have therefore been studied extensively in suicidal behavior research. However, only a few studies have described neuropsychological function impairment in suicidal patients. We investigated PFC-related neuropsychological function in patients with suicidal behavior, separating dorsolateral PFC (DLPFC)- and orbitofrontal cortex (OFC)-related functions. METHOD: We compared 30 euthymic patients with suicidal behavior aged 18-65 years with 39 control subjects, for the following neuropsychological domains: global intellectual functioning, reward sensitivity, initiation, inhibition, and working memory. Patients and controls were compared by means of univariate and multivariate analyses, adjusting for age at interview, level of education and mood state at the time of evaluation. Trait impulsivity, measured with the Barratt Impulsivity Scale version 10 (BIS-10), was also included as a covariate in a subset of analyses. RESULTS: Multivariate comparisons demonstrated significant executive function deficits in patients with suicidal behavior. In particular, we observed impairment in visuospatial conceptualization (p<0.0001), spatial working memory (p=0.001), inhibition (Hayling B-A, p=0.04; go anticipations, p=0.01) and visual attention (or reading fluency) (p=0.002). Similar results were obtained following adjustment for motor impulsivity as a covariate, except for spatial working memory. CONCLUSIONS: These deficits are consistent with prefrontal dysfunction in patients with suicidal behavior. Differentiation between DLPFC- and OFC-related neuropsychological functions showed no specific dysfunction of the orbitofrontal region in patients with suicidal behavior in our sample.

Adult↗
PubMed2006

Familial resemblance for executive functions in families of schizophrenic and bipolar patients.

Executive dysfunctions are considered to be putative markers of familial/genetic vulnerability to both schizophrenia and bipolar disorder. However, familial resemblance must be demonstrated before executive functions are used as a potential endophenotype. The aim of this study was to investigate familial resemblance for executive functions in families of schizophrenic and bipolar subjects. We assessed executive functions by means of two tests - the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT) - in 351 subjects from five populations: schizophrenic patients, bipolar patients, a group of relatives for each patient group and controls. For both tests, cognitive assessment results were consistent with previous studies: schizophrenic patients showed the greatest impairment, followed by bipolar patients and then the two groups of relatives. In families of bipolar patients we observed familial resemblance for the WCST and part A and part B of the TMT. However, by contrast with the classical point of view, considering executive measures to be markers of genetic vulnerability to schizophrenia, we did not demonstrate familial resemblance for either of the two executive tests in families of schizophrenic patients. Thus, executive measures, as assessed by the WCST or the TMT, should not be used as endophenotypes in genetic studies of schizophrenia unless confounders are identified and their effects eliminated.

Adult↗
PubMed2005

Suicidal disorders: a nosological entity per se?

An extensive body of data has repeatedly shown in the past decades that suicidal behaviors are associated with several external validators such as low serotonergic activity in body fluids and in brains of suicide victims, genetic transmission of suicide risk independently of transmission of associated major psychiatric disorders, and more recently association with several serotonin-related genes. Despite these concordant findings, suicidal behaviors are still not considered as a nosological entity per se in standardized classification. The aim of this study is to review the existing literature establishing the validity of this entity through clinical, genetic, biochemical, and therapeutic arguments all leading to the need to recognizing suicidal behavior as an independent and possibly dimensional clinical entity.

Brain↗
PubMed2005

Age at onset in bipolar affective disorders: a review.

Bipolar affective disorder (BPAD) is a multifactorial disorder with various clinical presentations. Etiologic heterogeneity may partly underlie the phenotypic heterogeneity. Efforts to dissect BPAD have been based on the course of the disorders (BP I versus BP II or rapid cycling), comorbidity pattern (panic attacks, suicide attempts, addiction or hyperactivity), differences between the sexes, and clinical pattern (cycloid and puerperal psychosis). The present article provides a comprehensive review of the existing data, showing that age at onset (AAO) identifies homogeneous sub-groups of patients with BPAD. Recent work has demonstrated the existence of three--early, intermediate and late--onset bipolar sub-groups based on AAO, following Kendell's criteria for validity (The American Journal of Psychiatry 2003; 160: 999). We will also show how these distinctions may be of use in the search for genetic vulnerability factors and other pathogenic influences. Following Kendell's criteria, we show that AAO of bipolar disorders has been tested with most of the available strategies for establishing the validity of clinical syndromes. We also present data from genetic epidemiologic studies in bipolar disorder, showing that AAO sub-groups may reduce the underlying genetic heterogeneity. No accurate AAO thresholds to define valid sub-groups have been identified precisely. Until recently, studies defined early- and late-onset as corresponding to early or mid-adulthood, not taking into account juvenile-onset bipolar disorder. A recently proposed theoretical model with three AAO sub-groups (onset age 17, 27 and 46) is discussed.

Adolescent↗
PubMed2005

Impaired decision making in suicide attempters.

OBJECTIVE: The understanding of suicidal behavior is incomplete. The stress-diathesis model suggests that a deficit in serotonergic projections to the orbitofrontal cortex is involved in susceptibility to suicidal behavior. The orbitofrontal cortex has been implicated in decision making, a cognitive function dealing with complex choices that may be under serotonergic modulation. In this preliminary study, the authors assessed decision making in suicide attempters. METHOD: The authors used the Iowa Gambling Task to investigate patients with a history of violent (N=32) or nonviolent (N=37) suicidal behavior, patients suffering from affective disorders with no history of suicidal behavior (N=25), and healthy comparison subjects (N=82). Patients were assessed when they were not suffering from a current axis I disorder. The authors also assessed the correlation of Iowa Gambling Task performance with psychometric measures of impulsivity, hostility, anger, aggression, and emotional instability. RESULTS: Both groups of suicide attempters scored significantly lower than healthy comparison subjects, and violent suicide attempters performed significantly worse than affective comparison subjects. No significant differences were observed between the groups of suicide attempters or between the two comparison groups. The differences in performance could not be accounted for by age, intellectual ability, educational level, number of suicide attempts, age at first suicide attempt, history of axis I disorder, or medication use. Iowa Gambling Task performances were correlated positively with affective lability and with anger expression but not with impulsivity. CONCLUSIONS: Impaired decision making, possibly due to emotional dysfunction, may be a neuropsychological risk factor for suicidal behavior.

Adult↗
PubMed2004

Admixture analysis of age at onset in schizophrenia.

In schizophrenia, clinical, familial and biological characteristics according to age at onset (AAO) suggest that AAO is a valid candidate symptom for genetic studies. However, none of the various thresholds used to define AAO subgroups in schizophrenia has been validated. We aim to define different AAO subtypes by admixture analysis in a sample of prospectively recruited subjects with schizophrenia. Consecutive inpatients and outpatients (N=141) meeting DSM IV criteria for schizophrenia were included. We used admixture analysis to investigate whether the observed AAO distribution consisted of a mixture of gaussian distributions and then compared clinical features and familial risks in the various groups of subjects. The model that best fitted the observed AAO distribution was a mixture of two gaussian distributions (mean+/-S.D.): (19.91+/-3.56 years) and (33.48+/-8.2 years), with a cutoff point at 28 years. The existence of two subgroups according to AAO was further confirmed by the different clinical and familial profiles of these subgroups. The early-onset group consisted predominantly of male patients, with non-paranoid subtypes and with a higher familial risk of schizophrenia spectrum disorders and affective disorders. The late-onset group of patients presented predominantly paranoid subtype, preponderance of females; they were more likely to be married and to have children. We identified two subgroups of schizophrenic subjects with different clinical and familial profiles. This study provides a mathematical validation of the existence of two subgroups defined by an onset of schizophrenia before or after 28 years. These results may have important implications for the search for schizophrenia susceptibility factors. Working with homogeneous subgroups defined on the basis of AAO may facilitate the identification of genetic vulnerability factors in schizophrenia.

Adult↗
PubMed2004

Lack of association between 5HT2A receptor gene haplotype, bipolar disorder and its clinical subtypes in a West European sample.

Bipolar affective disorder (BPAD) is a complex psychiatric disorder with a major genetic contribution. Abnormalities in serotonergic function have been implicated in its aetiology. The 5HT2A receptor (5HT2AR) gene is a strong candidate gene for involvement in BPAD, but previous association studies have reported conflicting results. These data are difficult to interpret because most negative results were obtained with small samples. The aim of this study was to test the association between the 5HT2AR gene and BPAD in a large West European sample. We studied the -1438G/A and the His452Tyr polymorphisms, for haplotype analysis to increase both informativity and the likelihood of detecting an association between BPAD and the 5HT2AR gene. We analysed the genotype, allele and haplotype distributions of two 5HT2AR gene variants in a population of 356 BPAD patients, which we compared with 208 healthy controls. We also carried out exploratory analysis in clinical subgroups of patients defined according to personal history of mood disorders, suicidal behaviour, comorbid psychiatric disorders and family history of affective disorders. We found no difference between BPAD patients and controls for allele, genotype and haplotype distributions. Exploratory analysis in subgroups of BPAD patients showed only a marginal difference in haplotype distribution between controls and BPAD patients with antidepressant-induced mania (P = 0.018). This difference was not significant after correction for multiple testing. Our study suggests that the 5HT2AR gene is unlikely to be involved in genetic susceptibility to BPAD but should be further investigated in a pharmacogenetic study.

Adult↗
PubMed2004

Association between the TPH gene A218C polymorphism and suicidal behavior: a meta-analysis.

Genes encoding proteins involved in serotonergic metabolism are major candidates in association studies of suicidal behavior. The tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, is a major candidate gene and has been extensively studied in association studies of suicidal behavior, providing conflicting results. It is difficult to interpret these conflicting results due to lack of power, ethnic heterogeneity, and variations in the sampling strategies (in particular for controls) and in the polymorphism of the TPH gene studied. Meta-analyses can improve the statistical power for the analysis of the effects of candidate vulnerability factors. The analysis of the sources of heterogeneity that contribute to these conflicting results is an important step in the interpretation of these conflicting association results and in the interpretation of the results of a meta-analysis. We selected all of the published association studies between the TPH gene polymorphism and suicidal behavior. Nine association studies between the A218C TPH polymorphism and suicidal behavior fulfilled the inclusion criteria. A significant association was observed between the A218C polymorphism and suicidal behavior using the fixed effect method (odds ratio (OR) = 1.62; 95% confidence interval (CI) = [1.26; 2.07]) and the random effect method (OR = 1.61; 95% CI = [1.11; 2.35]). The analysis of the sources of heterogeneity showed that two studies (one positive and one negative) significantly deviated from the calculated global effect. The meta-analysis performed after removing those two studies also revealed a significant association between the TPH A218C polymorphism and suicidal behavior. Both analyses suggested that the A allele has a dose-dependent effect on the risk of suicidal behavior.

Alleles↗
PubMed2004

Serotonin transporter gene may be involved in short-term risk of subsequent suicide attempts.

BACKGROUND: In the first year following a suicide attempt, patients are at high risk for reattempt and for completed suicide. We aim to determine the predictive value of two serotonin-related genes, the tryptophan hydroxylase (TPH) and serotonin transporter (5-HTTLPR) genes that have been involved in the susceptibility to suicidal behavior. METHODS: After a one-year follow-up study of 103 patients hospitalized after a suicide attempt, patients have been genotyped for both the A218C TPH and the functional S/L 5-HTTLPR polymorphisms. RESULTS: Patients who reattempted suicide during the follow-up period had significantly higher frequencies of the S allele and the SS genotype. The odds ratio for the SS genotype vs. the LL genotype was 6.5 (95% CI [1.18-35.84]). No difference was observed for TPH gene. Patients carrying the SS genotype were more impulsive. However, multivariate analysis suggested an independent effect of both the SS genotype and impulsivity on the risk of repeated suicide attempts. CONCLUSIONS: These results suggest that the 5-HTTLPR SS genotype is associated with further suicide attempts among patients who have previously attempted suicide.

Adult↗
PubMed2004

Executive dysfunctions as potential markers of familial vulnerability to bipolar disorder and schizophrenia.

Attentional and executive impairments have been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that they might be considered as familial vulnerability markers. Several studies have shown that the performance of bipolar patients does not significantly differ from that of schizophrenic patients, so that executive and attentional deficits might not be specific to schizophrenia. In the present study, we aimed to identify executive dysfunctions in schizophrenia and bipolar disorder that might be vulnerability trait markers specific to one or common to both of these diseases. We assessed cognitive performance of euthymic bipolar and schizophrenic patients, their unaffected first-degree relatives and a healthy control group, using neuropsychological tasks to test different components of executive function: the Verbal Fluency Test, the Stroop Word Colour Test, the Wisconsin Card Sorting Test and the Trail Making Test. The two groups of patients and their unaffected relatives demonstrated disproportionately increased slowness on the Stroop test in comparison to the normal healthy group. Patients with schizophrenia performed poorly on all the tests in comparison to the normal healthy subjects, while no other impairment was observed in the bipolar patients and in the relatives of schizophrenic and bipolar patients. Enhanced susceptibility to interference and reduced inhibition could be transnosographical markers for a shared familial vulnerability common to schizophrenia and bipolar disorders.

Adult↗
PubMed2004

Bipolar patients with suicidal behavior: toward the identification of a clinical subgroup.

BACKGROUND: Suicide is the most severe and frequent complication of bipolar disorder, but little is known about the clinical characteristics of bipolar patients at risk of suicide. The purpose of this study was to identify those characteristics. METHOD: We studied 307 prospectively recruited DSM-IV-diagnosed bipolar I or II patients from November 1994 through October 2001. Semi-structured diagnostic interviews (the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies) were used to determine the diagnosis of bipolar disorder and its lifetime description, lifetime comorbid Axis I disorder diagnoses, familial history of psychiatric disorders and demographic characteristics. RESULTS: One hundred twenty-nine bipolar patients (42%) had made at least 1 suicide attempt in their life. Lifetime history of suicidal behavior was associated with history of suicidal behavior in first-degree relatives but not with a familial history of mood disorder. Early age at onset of mood disorder, total number of previous depressive episodes, alcohol and tobacco use, social phobia, antidepressant-induced mania, and personal history of head injury were associated with suicidal behavior. No association was observed with gender or diagnosis of bipolar I or II disorder. Social phobias, tobacco use, and personal history of head injury were no longer associated with suicidal behavior in the multivariate analysis. CONCLUSION: Bipolar patients with early age at bipolar disorder onset, high number of depressive episodes, personal history of antidepressant-induced mania, comorbid alcohol abuse, and suicidal behavior constitute a clinical subgroup at risk of suicidal behavior. This information, as well as familial history of suicide behavior, should improve suicide risk assessment in bipolar patients.

Adult↗
PubMed2003

Anhedonia in schizophrenia: a distinct familial subtype?

Failures to replicate results in psychiatric genetics might be due to our inability to define the heritable phenotype. Instead of relying entirely on classical nosographical approaches, the use of a candidate symptom approach to identify more homogeneous forms of diseases among affected subjects and subclinical traits among first-degree relatives may increase genetic validity. Anhedonia may be a marker for subjects at risk of schizophrenia or schizophrenia spectrum disorders. We compared the familiality of anhedonia characterized by a high level of physical anhedonia (score above 23) in a sample of schizophrenic probands (N=80) and their relatives (N=78), with that in bipolar patients (N=109), their relatives (N=33) and normal controls (N=94). We identified a subform of schizophrenia characterized by highly anhedonic schizophrenic probands with a three-fold higher familial risk of schizophrenia and schizophrenic spectrum disorders. We also found that their first-degree relatives had a high level of anhedonia. An intrafamilial correlation analysis confirmed the familial nature of anhedonia. Our data suggest that anhedonia is a candidate symptom for schizophrenia. Refining phenotype definition by studying subgroups of anhedonic and non-anhedonic probands with relevant candidate genes might be fruitful.

Adult↗
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↗