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Marie-Odile Krebs

Publications and source records attributed to Marie-Odile Krebs.

At least 19 recordsLinked to original sources
PubMed2006

The French version of the validated short TEMPS-A: the temperament evaluation of Memphis, Pisa, Paris and San Diego.

The TEMPS developed from classical temperament concepts at the Universities of Tennessee (Memphis) and California (San Diego) in collaboration with clinical scientists in Pisa and Paris. It presently exists in 20 languages and full validation of its 110-item version has been accomplished in American English, Italian, French, German, Hungarian, Japanese, Turkish, Lebanese Arabic and Argentinean Spanish. For many studies, a shorter version is easier to use. Accordingly, the 39-item validated English version has just been rendered into French, to facilitate clinical use and research in Francophone countries.

France↗
PubMed2006

Association study of the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia.

BACKGROUND: Brahma (BRM) is a key component of the multisubunit SWI/SNF complex, a complex which uses the energy of ATP hydrolysis to remodel chromatin. BRM contains an N-terminal polyglutamine domain, encoded by a polymorphic trinucleotide (CAA/CAG) repeat, the only known polymorphism in the coding region of the gene (SMARCA2). We have examined the association of this polymorphism with schizophrenia in a family-based and case/control study. SMARCA2 was chosen as a candidate gene because of its specific role in developmental pathways, its high expression level in the brain and some evidence of its association with schizophrenia spectrum disorder from genome-wide linkage analysis. RESULTS: Family-based analysis with 281 complete and incomplete triads showed that there is no significant preferential transmission of any of the alleles to the affected offspring. Also, in the case/control analysis, similar allele and genotype distributions were observed between affected cases (n = 289) and unaffected controls (n = 273) in each of three Caucasian populations studied: French Canadian, Tunisian and other Caucasians of European origin. CONCLUSION: Results from our family-based and case-control association study suggest that there is no association between the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia.

Case-Control Studies↗
PubMed2006

Postnatal effect of embryonic neurogenesis disturbance on reelin level in organotypic cultures of rat hippocampus.

Despite a delayed emergence of the symptoms, schizophrenia is thought to be a late consequence of early disturbances during development. Several reports have found decreased levels of reelin in the cortex and the hippocampus of postmortem brains of schizophrenic patients. In the rat, intraperitoneal injection of the anti-mitotic agent methylazoxymethanol (MAM) during intra-uterine development (embryonic day 17) induces cytoarchitectural abnormalities in the hippocampus and the cortex and behavioural changes reminiscent of positive, negative and cognitive symptoms of schizophrenia. We aimed to examine whether a transient prenatal disturbance of neurogenesis induces postnatal changes in the expression of reelin in the hippocampus. Cellular modifications were explored using hippocampal organotypic slice cultures, which allow for conservation of the in vivo cytoarchitecture. MAM effect on hippocampal neurogenesis was confirmed by birthdating experiments. After 3 weeks in vitro, reelin was expressed by calretinin-negative cells. The number of reelin-positive neurons was increased whereas the total neuron number was decreased in the stratum oriens in the E17 MAM-exposed animals as compared to the control group. Not only an increase in the number of cells expressing reelin was observed, but there was also a slight increase in reelin mRNA levels in hippocampal pyramidal cells of MAM-exposed animals. In contrast, there was no significant change in the dentate gyrus. These results show that transient prenatal disturbance of neurogenesis induces long-term modifications in specific areas of the hippocampus and in particular in the number of neurons expressing reelin. They also confirm the value of organotypic slices to study postnatal maturation in the hippocampus.

Animals↗
PubMed2005

Validity of the CAGE questionnaire in schizophrenic patients with alcohol abuse and dependence.

The objective of the study was to assess the sensitivity and the specificity of the CAGE questionnaire in 114 schizophrenic patients. The Composite International Diagnostic Interview was used to assess the DSM-III-R diagnosis of abuse of or dependence on alcohol. The CAGE questionnaire can be reliably used to assess alcohol use disorders in schizophrenic patients: with a cutoff score of 1 or more, the sensitivity of the CAGE questionnaire was 0.91 and the specificity was 0.83. With a cutoff score of 2 or more, the sensitivity of the CAGE questionnaire was 0.82 and the specificity was 0.94. The post test probabilities (PPV) were high (PPV1=0.74; PPV2=0.85) compared to the primary probability of alcoholism (29.8%).

Adult↗
PubMed2005

Age at onset of schizophrenia: interaction between brain-derived neurotrophic factor and dopamine D3 receptor gene variants.

One of the main features of schizophrenia is its age at onset in early adulthood. Dopaminergic dysregulation is the most documented neurobiological factor that may be involved in triggering schizophrenia. Recent findings on neurodevelopmental processes show that the brain-derived neurotrophic factor plays a critical role in the development of mesolimbic dopaminergic-related systems and regulates the expression of dopamine D3 receptors. In this study, we examine whether an interaction between dopamine D3 receptors and brain-derived neurotrophic factor gene variants influences age at onset in patients with schizophrenia. Our findings show that this gene-gene interaction was significantly associated with an earlier emergence of psychosis by 3 years.

Adult↗
PubMed2005

Population-based and family-based association study of 5'UTR polymorphism of the reelin gene and schizophrenia.

Reelin is a glycoprotein involved in the migration and positioning of proliferating neurons and synaptic connectivity during neurodevelopment. It may also modulate neuronal plasticity throughout life. Therefore, the reelin gene is a candidate gene for schizophrenia. We examined the association of the CGG repeat polymorphism in the 5'-untranslated region of the reelin gene with schizophrenia in 266 unrelated French Caucasian patients, 156 of their parents, and 103 controls. We found no difference in the allele distribution between patients and controls although there was a significant higher prevalence of the genotype 8-8 in controls (CLUMP T3: chi(2) = 6.3, P = 0.035). There was no significant transmission disequilibrium in intrafamilial analysis. To refine our phenotypic characterization and in accordance with converging evidence suggesting that treatment resistance is associated with indices of abnormal neurodevelopment, we studied the association between reelin gene polymorphism and response to antipsychotics. Patients who responded to antipsychotics had a higher frequency of both the (CGG)(10) allele and (CGG)(10)-containing genotypes (P = 0.02; P = 0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]). Our results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia.

5' Flanking Region↗
PubMed2005

Admixture analysis of age at onset in obsessive-compulsive disorder.

BACKGROUND: Age at onset (AAO) has been useful to explore the clinical, neurobiological and genetic heterogeneity of obsessive-compulsive disorder (OCD). However, none of the various thresholds of AAO used in previous studies have been validated, and it remains an unproven notion that AAO is a marker for different subtypes of OCD. If AAO is a clinical indicator of different biological subtypes, then subgroups based on distinct AAOs should have separate normal distributions as well as different clinical characteristics. METHOD: Admixture analysis was used to determine the best-fitting model for the observed AAO of 161 OCD patients. RESULTS: The observed distribution of AAO in OCD is a mixture of two Gaussian distributions with mean ages of 11.1 +/- 4.1 and 23.5 +/- 11.1 years. The first distribution, defined by early-onset OCD, had increased frequency of Tourette's syndrome and increased family history of OCD. The second distribution, defined by late-onset OCD, showed elevated prevalence of general anxiety disorder and major depressive disorder. CONCLUSIONS: These results, based on a statistically validated AAO cut-off and those of previous studies on AAO in OCD, suggest that AAO is a crucial phenotypic characteristic in understanding the genetic basis of this disorder.

Adolescent↗
PubMed2005

Future contributions on genetics.

It has become obvious from epidemiological studies in families of patients affected or from twin studies, that most psychiatric disorders are in part genetically determined. Genetics have raised incredible hopes that the complex nature of psychiatric disorders might be unravelled. However, progress in psychiatry genetics have met major difficulties that have hampered psychiatry taking advantage of the new technologies as compared to other fields, such as neurology. In this non-exhaustive review, we propose an overview from the initial evidence to the expected future, through a critical statement on the current situation.

Bipolar Disorder↗
PubMed2005

[Schizophrenic disorders: current etiologic and clinical knowledge].

Brain anomalies associated with schizophrenic disorders may be of a cognitive, neurophysiological or neurological nature [the latter being relatively minor and nonspecific]. Brain imaging has revealed early anomalies such as cortical-subcortical atrophy and abnormal gyration. These anomalies can also be present in relatives free of schizophrenic symptoms. This raises the question of what determines the transition from vulnerability to clinical onset. There is now evidence that schizophrenic disorders are true brain diseases. This is based on neuropathological studies, brain imaging and clinical findings such as "soft" neurological signs (pyramidal and extrapyramidal symptoms, coordination difficulties, etc.). Cognitive dysfunctions such as attention and memory disorders and abnormal verbal fluency have also been described. Oculomotor pursuit and auditive evoked potentials have identified specific neurophysiological disorders such as N300 and P50 wave modifications. Schizophrenic disorders can also be associated with neuronal abnormalities, notably affecting factors involved in synaptic transmission and plasticity. For example, BDNF protein deficit is linked to certain late-onset forms of schizophrenia. Genetic studies are no longer focusing on a possible disease genotype but rather on phenotypic characteristics determined by simpler genotypes (P50 wave modulation, COMT and BDNF genes). The ultimate objective is to identify high-risk subjects, in order to shorten the treatment delay and thereby improve long-term outcome. The benefit of primary prophylaxis remains to be determined, however.

Brain↗
PubMed2004

Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia.

Schizophrenia is associated with impairments in many cognitive domains on which the influence of antipsychotics, whether conventional or atypical, remains unclear. We conducted a study of recent-onset schizophrenic patients (DSM IV) that included unmedicated (n=19), and medicated (n=19) patients matched for age and IQ. Both groups of patients had comparably low extra-pyramidal symptoms (EPS). Cognitive tasks included attentional tasks (alertness and divided attention tests), a working memory task (a verbal n-back test) and the Wisconsin Card Sorting Test (WCST). After adjustment for the Total PANSS score, we found no significant difference between the two groups of patients in any of the cognitive tasks. When compared to a group of healthy controls (n=20) matched for IQ level, unmedicated patients performed significantly worse in all cognitive tasks, with significantly longer reaction times for alertness, divided attention and working memory. These results confirm the presence of cognitive impairments in attentional and executive functions in recent-onset patients whether or not they are medicated. There was no evidence that either conventional or atypical antipsychotics had an influence on patients when EPS were excluded. Altogether, our results further support the idea that cognitive deficits in schizophrenia are enduring features per se and cannot be considered as secondary to psychiatric symptoms or to the adverse effects of medication. In addition our results suggest that antipsychotics do not have a major effect on these impairments.

Adult↗
PubMed2004

Nicotine use in schizophrenia and disinhibition.

The role of personality in nicotine use has been little studied in patients with schizophrenia. The objectives of the present study were to compare impulsivity, sensation seeking and anhedonia in a group of schizophrenic patients with and without current cigarette smoking. One hundred patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria) were assessed with the Positive and Negative Syndrome Scale, the Fagerström Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. Among these patients, 67% were current smokers. The mean scores for sensation seeking were higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the "disinhibition" subscale. No significant difference was found for impulsivity and physical anhedonia mean scores. The scores on the Sensation Seeking Scale were especially low in nonsmokers. Cigarette smoking could influence disinhibition and possibly help to normalize inhibition in schizophrenic patients.

Adult↗
PubMed2004

Cerebellum development and schizophrenia: an association study of the human homeogene Engrailed 2.

Epidemiological data and family studies in schizophrenia show that genetic factors contribute to the vulnerability to this disorder. The homeogene Engrailed 2 (EN2) is specifically involved in patterning the region that gives rise to the cerebellum and controls the plasticity of midbrain dopaminergic neurons. We carried out an association study for a CA repeat polymorphism located in the 3' region of the homeogene EN2. The subjects consisted of 165 patients with schizophrenia and 97 controls matched for age and ethnicity from a French Caucasian population. We found no significant association of schizophrenia with this bi-nucleotide repeat polymorphism of the EN2 gene.

Adult↗
PubMed2004

Effects of atypical neuroleptics on alertness and visual orienting in stabilized schizophrenic patients: a preliminary study.

It has been shown that schizophrenic patients treated with conventional neuroleptics display a general slowness in latency in simple reaction-time tasks and a disengagement deficit in visual-orienting tasks. Yet, the influence of atypical neuroleptics on attention is still controversial. The purpose of our study was to investigate the effect of atypical neuroleptics in tasks requiring alertness, selective attention or visual orienting. Thirteen stabilized schizophrenic patients receiving atypical neuroleptics were compared to 13 healthy controls matched for age, gender, and study level, in a choice reaction time (CRT) task and a visual-orienting task cued target detection (CTD) task. The results showed that patients and controls obtained comparable reaction times (RTs) in the CRT task. In the CTD task, both groups had comparable RTs but the presence of invalid cues caused a greater attentional cost in both visual fields for patients compared to controls, indicating a symmetrical disengagement deficit. To conclude, patients treated with atypical neuroleptics had a phasic alertness ability similar to controls. By contrast, an impairment of disengagement was present in those patients. Thus, atypical neuroleptics could have a positive influence on certain but not all attentional domains.

Adult↗
PubMed2004

Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder.

Several lines of evidence suggest that obsessive compulsive disorder (OCD) could be the consequence of glutamatergic dysfunction. We performed a case-control study in 156 patients and 141 controls and the transmission disequilibrium test in 124 parent-offspring trios to search for association between OCD and two kainate receptors, GRIK2 and GRIK3. Using three single nucleotide polymorphisms (SNP) in GRIK2 and one in GRIK3, we found no evidence for association in case-control or family-based analyses. Only the GRIK2 SNP I867, recently associated with autism, was less transmitted than expected (p < 0.03), supporting a functional role for this variant. These findings suggest the need for further investigation of the role of GRIK2 in OCD.

Adolescent↗
PubMed2004

Minor physical anomalies in patients with schizophrenia and their parents: prevalence and pattern of craniofacial abnormalities.

The frequency of minor physical anomalies (MPAs) in patients with schizophrenia suggests an early disturbance in the development of the neuroectoderm. To improve the phenotypic delimitation of this disorder, we used a comprehensive scale of MPAs (41 items) in patients with schizophrenia and their first-degree relatives. This scale, adapted from a revised version of the Waldrop Scale (Ismail et al. Minor physical anomalies in schizophrenic patients and their siblings, American Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing facial and limbs asymmetry. The interrater reliability between two examiners was good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45; mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of several items to predict group status, including facial asymmetry, cleft palate, hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry in patients with schizophrenia and their first-degree relatives provides new insights into the underlying dysembryogenic processes. This revised scale thus appears to be a useful complementary tool in pathophysiological studies aiming at the identification of developmental factors in schizophrenia.

Abnormalities, Multiple↗
PubMed2003

Neurological soft-signs and minor physical anomalies in schizophrenia: differential transmission within families.

Markers of vulnerability have been identified in schizophrenia, and among them, neurological soft-signs (NSS) and minor physical anomalies (MPAs) also seem to occur in biological relatives. The similarities of these developmental markers within families may depend on either genetic or non-genetic factors. The aim of the study was to investigate the intra-familial similarities of NSS and MPAs within 18 nuclear families (18 probands with schizophrenia and 36 of their non-psychotic parents). A general linear model showed similarities within families for NSS (intra-class coefficient [ICC] = 0.64; F = 2.6; df = 17.17; p = 0.02) but not for MPAs (ICC = -0.10; F = 0.7; df = 17.17; ns). We thus found a direct evidence for the intra-familial transmission of NSS but not of MPAs, suggesting that this morphological phenotypic trait could be more dependent on epigenetic influences.

Abnormalities, Multiple↗
PubMed2003

Apolipoprotein E in schizophrenia: a French association study and meta-analysis.

Schizophrenic disorders are complex genetic disorders that may involve multiple genes of small effect. Apolipoprotein E (ApoE) gene variants are associated with alterations in brain function and an increased risk of Alzheimer's disease (AD). However, conflicting results have been reported in schizophrenia. We compared the ApoE genotypes of 114 French Caucasian schizophrenic patients and 91 normal controls. No differences in ApoE allele or genotype frequencies were observed between the two groups. However, we observed a possible association between male schizophrenic patients and the ApoE epsilon 2 epsilon 3 genotype. In addition, a meta-analysis of all published case-control studies on ApoE and schizophrenia did not support a major role for ApoE gene variants in schizophrenia as a whole. However, ApoE may be associated with particular forms of schizophrenia.

Alleles↗