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Biomedical subjects

F Thibaut

Publications and source records attributed to F Thibaut.

At least 19 recordsLinked to original sources
PubMed2005

Hyperprolinemia is a risk factor for schizoaffective disorder.

DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.

Adult↗
PubMed2004

The promoter -194 C polymorphism of the nicotinic alpha 7 receptor gene has a protective effect against the P50 sensory gating deficit.

As suggested by several studies, abnormal sensory gating measured by the P50 paradigm could be an endophenotype predisposing to schizophrenia. In a previous work, we have shown a significant association between the presence of at least one -2 bp deletion located within exon 6 of the CHRNA7-like gene and the P50 abnormality in the general population. A recent study involved polymorphisms located in the core promoter region of the CHRNA7 gene as risk factors for the P50 inhibitory deficit. Screening for promoter variants in a large population of schizophrenic patients (n=111) and control subjects (85), for whom auditory-evoked potentials had been recorded did not allow us to replicate these results. By contrast, we showed a significant association between the -194 C allele and a T/C ratio <0.45, thus demonstrating a protective effect of this variant for the sensory gating deficit. Such conflicting results can be reconciled if we consider that the -194 C polymorphism has no causative effect, but is in linkage disequilibrium with other causal variations for the P50 sensory gating deficit, and that different alleles are in disequilibrium in different populations.

Adult↗
PubMed2002

Cognitive patterns in subtypes of schizophrenia.

AIM: Because of the heterogeneity of schizophrenia, this study researched different cognitive patterns in distinct subtypes of schizophrenic patients. METHODS: Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic patients and 35 healthy controls were included. Patients were categorized into deficit, disorganized and positive subtypes with the schedule for the deficit syndrome (SDS) and the positive and negative syndrome scale (PANSS). Executive/attentional functions were assessed with the modified card sorting test (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop color-word test (Stroop test). Episodic memory was explored through the California verbal learning test (CVLT). RESULTS: The positive subtype had some executive/attentional (fluency and Stroop tests) and mnesic performances in the normal range, suggesting the preservation of good cognitive skills. In contrast, the deficit and disorganized subtypes had major mnesic and executive/attentional dysfunctions compared to healthy subjects. The deficit subtype compared to the control group performed predominantly worse on the MCST and fluency, whereas the disorganized subtype had the lowest scores on the TMT and the Stroop test. CONCLUSION: This study showed distinct cognitive patterns in deficit, disorganized and positive patients in comparison with the controls, suggesting a heterogeneous cognitive dysfunction in schizophrenia.

Adolescent↗
PubMed2002

The -2 bp deletion in exon 6 of the 'alpha 7-like' nicotinic receptor subunit gene is a risk factor for the P50 sensory gating deficit.

Abnormality in the P50 auditory-evoked potential gating is an endophenotype associated with schizophrenia. Biochemical and genetic studies have suggested that the alpha 7 nicotinic acetylcholine receptor (nAChR) is involved in this sensory gating deficit. Two related alpha 7 genes (CHRNA7 and CHRNA7-like gene) resulting from a partial duplication (from exon 5 to exon 10) are present in the human genome. Two types of genetic variation, a large deletion and a -2 base-pair deletion in exon 6 resulting in a truncation of the open reading frame, affect specifically the CHRNA7-like gene. We developed a simple multiplex PCR assay on genomic DNA, allowing the quantification of the number of exons 6 and the distinction of all possible exon 6 genotypes. Genotyping of 70 schizophrenic patients and 77 controls showed that carrying at least one -2 bp deletion of exon 6 did not constitute a risk factor for schizophrenia. In contrast, the distribution of genotypes differed significantly between subjects with normal and abnormal P50 ratios, with an over-representation of genotypes carrying at least one -2 bp deletion of exon 6 among subjects exhibiting an abnormal P50 ratio. We thus conclude that the -2 bp deletion within the CHRNA7-like gene is a risk factor for P50 sensory gating deficit. Interestingly, most of the effect came from the non schizophrenic group, which may suggest that in schizophrenic patients other risk factors account for the large proportion of subjects exhibiting an abnormal P50 ratio.

Adult↗
PubMed2001

No evidence for linkage between COMT and schizophrenia in a French population.

Catechol-O-methyltransferase is a candidate in the predisposition to schizophrenia both because of its function and the position of its gene. A multipoint non-parametric linkage analysis and a transmission disequilibrium test were performed on 42 multiplex families genotyped for Pml I and Bcl I polymorphisms using two definitions of the affected phenotype. Neither linkage nor preferential transmission of any allele or haplotype was detected, failing to replicate previous positive findings.

Alleles↗
PubMed2001

Concordance of deficit and non-deficit subtypes in siblings affected with schizophrenia.

Deficit and non-deficit subtypes were examined for their concordance in 83 sibling pairs of 109 schizophrenic patients belonging to 46 multiply affected families. Using a sib-pair method, we have found that the distribution of deficit and non-deficit syndromes in sibling pairs of schizophrenic patients differed significantly from chance expectation. This familial aggregation suggests that the syndrome may be used to define phenotypes for genetic studies.

Adult↗
PubMed2001

Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia.

We have analyzed eye movement performances in schizophrenics showing primary negative or deficit symptoms (n=16) and non-deficit schizophrenics (n=55), and compared them with those of controls (n=34) in order to study the relationships between negative symptoms and eye movement abnormalities. Patients were subtyped into deficit and non-deficit subgroups using the Schedule for the Deficit Syndrome. Three oculomotor paradigms were used: smooth pursuit, a reflexive saccade paradigm and an antisaccadic task. The smooth pursuit gain was significantly decreased (and the rate of catch-up saccades increased) in schizophrenics as compared with controls, but no difference was observed between patient groups. In the reflexive saccade paradigm, no difference was found between controls and patients, except for latency in deficit patients. In the antisaccade paradigm, the number of errors and the latency of successful antisaccades were significantly increased in schizophrenics as compared with controls. The latency of successful antisaccades in both directions was significantly increased in deficit patients as compared with non-deficit patients. The latency of rightward successful antisaccades was significantly increased as compared with the latency of leftward antisaccades in deficit patients only. However, when patients were classified into negative and non-negative groups using the PANSS, no difference was found in the antisaccade paradigm. Smooth pursuit impairment does not seem to depend on the primary enduring negative symptoms.In deficit schizophrenics, the abnormalities observed in the antisaccadic task are consistent with prefrontal dysfunction, and may suggest parietal lobe dysfunction as well.

Adult↗
PubMed2001

Evidence of a cohort effect for age at onset of schizophrenia.

OBJECTIVE: The authors address whether a possible age-at-onset cohort effect may have introduced a bias into anticipation studies of schizophrenia. METHOD: A retrospective review of the medical records of all admissions for psychotic disorders (N=877) was conducted. All subjects with a confirmed DSM-IV diagnosis of schizophrenia and age-at-onset data were included (N=419). For analyses, subjects were placed into one of three successive birth cohorts: 1905-1944 (N=96), 1945-1964 (N=200), and 1965-1984 (N=123). RESULTS: The mean age at first appearance of psychotic symptoms and, similarly, the mean age at first hospitalization significantly decreased over time in successive birth cohorts (25.3, 23.3, and 20.4 years, respectively, for age at first appearance of psychotic symptoms). CONCLUSIONS: This potential birth cohort effect for age at onset of schizophrenia needs to be incorporated into genetic models.

Adult↗
PubMed2000

Proton magnetic resonance spectroscopy of the medial prefrontal cortex in patients with deficit schizophrenia: preliminary report.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) was used to study medial prefrontal metabolic impairments in schizophrenic patients with the deficit syndrome. METHOD: The subjects were 22 schizophrenic patients categorized as deficit (N=5) or nondeficit (N=17) and 21 healthy subjects. (1)H-MRS was performed for the right and the left medial prefrontal cortex. RESULTS: The patients with the deficit syndrome had significantly lower ratios of N-acetylaspartate to creatine plus phosphocreatine than did the healthy subjects or nondeficit patients. CONCLUSIONS: As N-acetylaspartate levels could reflect neuronal density and/or viability, this finding suggests a neuronal loss in the medial prefrontal cortex of deficit patients.

Aspartic Acid↗
PubMed1999

Linkage disequilibrium on the COMT gene in French schizophrenics and controls.

Catechol-O-methyltransferase (COMT) catalyzes the degradation of catecholamines and could therefore play a role in the etiology of schizophrenia. Moreover, microdeletions including the COMT locus have been found in schizophrenics presenting typical features of the velo-cardio-facial syndrome. In the present work, five single-strand conformation polymorphisms were detected in exons of the COMT gene. The linkage disequilibria between the polymorphisms were estimated, and the genotypic frequencies were calculated on a sample of 126 to 137 schizophrenics and 136 to 140 controls, depending on the marker. Patients and controls were matched for ethnicity and geographical origin. A trend toward association was found between schizophrenia and (i) genotype 11 of the Pml I polymorphism (p = 0.034; OR = 1.82); (ii) haplotype 1-2 for the Pml I and Bcl I polymorphisms (p = 0.022; OR = 1.75). The Pml I polymorphism is in complete linkage disequilibrium with the common Met-->Val(158) substitution, which affects the activity of the enzyme. This finding suggests a possible minor effect of COMT in a multifactorial threshold model of vulnerability to schizophrenia.

3' Untranslated Regions↗
PubMed1999

Month of birth in deficit and non-deficit schizophrenic patients.

In order to test the hypothesis that an excess of summer births is a risk factor for deficit syndrome, the month of birth was studied in 53 deficit schizophrenic patients compared to 158 non-deficit patients. No significant difference in terms of month of birth or season of birth was observed between deficit and non-deficit patients, suggesting that summer births might not be a risk factor for deficit schizophrenia.

Adult↗
PubMed1999

Apolipoprotein E-varepsilon4 frequency in deficit schizophrenia.

The apolipoprotein E (ApoE) genotype has been found to affect the expression of several neuropsychiatric disorders. We determined ApoE genotype frequencies and their relationship to primary negative symptoms in 61 non-deficit and 45 deficit schizophrenic patients, and compared them with 98 control subjects. No difference was observed when genotype or allele frequencies were compared between the three groups. Our data do not support a role for ApoE in the phenotypic expression of schizophrenia.

Adult↗
PubMed1998

Anticipation in schizophrenia: no evidence of expanded CAG/CTG repeat sequences in French families and sporadic cases.

A decrease in age of onset of schizophrenia through consecutive family generations (anticipation) has been found in several studies. Anticipation is known to result from expansion of CAG repeats in genes that determine several neurodegenerative disorders. In a previous study we analysed 26 unilineal two-generation French pedigrees and found clinical evidence of anticipation. A 10-year mean reduction in age of onset of schizophrenia was found in the second generation compared with the parental generation. The repeat expansion detection method was used to screen for CAG expansion in 21 of the 26 families with evidence of anticipation for the disease and in 59 sporadic schizophrenics and 59 controls. Comparison of the frequency distributions of CAG/CTG repeat size observed in schizophrenics and controls showed no significant difference, even when we considered familial (P = 0.23) and sporadic (P = 0.25) affected individuals separately. These results do not support the association between long CAG repeats and schizophrenia. However, the possibility that expansions with fewer than 40 repeats are involved in schizophrenia cannot be excluded.

Adult↗