The sensitivity of denaturing gradient gel electrophoresis: a blinded analysis.

Denaturing gradient gel electrophoresis (DGGE) is considered one of the most sensitive and specific of the mutational scanning techniques, yet blinded analyses have not been reported. We report the results of a blinded study of the efficiency of DGGE to detect mutations in the Human Coagulation Factor IX. Two overlapping genomic DNA sequences from exon 8 of Factor IX (290 bp and 539 bp length) with an unknown number of mutations were amplified with a 40 bp GC-clamp and tested blindly by DGGE. DGGE detected all mutations in the 290 bp genomic DNA segment. DGGE detected all but one mutation in the 539 bp genomic segment after experimental conditions were fully optimized but missed multiple mutations in an initial blinded experiment. These results demonstrate the utility of blinded analyses and confirm the exquisite power of DGGE for detecting mutations.

[Disposition toward mood genes]. / Des humeurs aux gènes de l'humeur.

Genetic factors together with psychological heredity have been involved in the genesis of mood disorders for a long time. Beside chromosomes X and 11, many other tracks exist. Results are heterogeneous and likely because of clinical, etiopathogenic and genetic heterogeneity of these diseases. Studies multiplicity strengthen the determinism complexity of the mood disorders. Since positive results published remain poorly replicated they receive from readers a reception as variable as the mood changes of the illnesses they concern. However, these studies lead to a better definition of their limits. Either clinical, biological or genetic, these limits would be on the decline and human genetic applied to psychiatry might improve etiopathogenic and therapeutic knowledges of mood disorders.

No abnormality in the gene for the G protein stimulatory alpha subunit in patients with bipolar disorder.

BACKGROUND: The available evidence for an involvement of the heterotrimeric guanine-nucleotide-binding proteins (G proteins) in bipolar disorder relies primarily on the effects of lithium salts on G protein function and on alterations in the concentration or function of G proteins (most notably Gs-alpha) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder. METHODS: The hypothesis that a mutation in Gs-alpha gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the Gs-alpha subunit gene coding sequences and promoter sequences by denaturing gradient gel electrophoresis in unrelated individuals with bipolar disorder and (2) association and linkage analyses with a common silent exonic polymorphism, using genetic allelic information from American families with at least 1 affected child. For association analysis, the transmission test for linkage disequilibrium was used; for linkage analysis, nonparametric methods were used. RESULTS: No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative. CONCLUSION: Our results do not support the speculation that the Gs-alpha protein gene has a role in the genetic predisposition to bipolar disorder.

[Premenstrual dysphoric disorder: diagnostic and therapeutic approach]. / Trouble dysphorique prémenstruel: approche diagnostique et thérapeutique.

Central Nervous System acts as both a target and a regulator for the hormonal system. Premenstrual syndrome is a good example. Premenstrual dysphoria is wellknown and dreaded since a long time. Recent diagnostic criteria available for Premenstrual Dysphoric Disorder decrease the methodologic problems and might lead to a better knowledge regarding etiology and treatment. Alteration of serotonin regulation seems to be a promising area for further research. Efficacy of the inhibitors of serotonin reuptake accounts for it. Expected improvements will benefit to women and men as well....

[Criteria for choosing antidepressants]. / Critères de choix d'un antidépresseur.

Since clinical and biological 'markers' in depressive disorders are missing, the antidepressive drug choice today is based on several classifications. The chemical classification separates antidepressive drugs according to their structure. Their activity mechanism and/or specificity on brain neurotransmittors constitute the biochemical classification. Their sedative, median or stimulating activity provide the therapeutic classification. Which criteria should be used in choosing? The choice depends on clinical and biological data obtained from the patient. Chemical classification may be useful at a new molecule synthesis level. In the biochemical classification, anticholinergic and antihistaminic activities inducing side effects and sedation are taken in account. The therapeutic classification is usually used first, especially in case of first cure. An antidepressive drug will be prescribed according its initial effects on anxiety or holding up, facilitating the wait for its antidepressive action. A better definition of samples studied and of study aims, and improvement in knowledge about activity mechanisms of antidepressive drugs might provide answers regarding treatment choice in depressive disorders.

Genetic study of dopamine D1, D2, and D4 receptors in schizophrenia.

The goal of this study was to define precisely the involvement of the dopamine D1, D2, and D4 receptor genes in the etiology of schizophrenia. A linkage analysis using the lod score method was performed in 37 families originating from France (n = 14) and from the Island of La Réunion in the Indian Ocean (n = 23). No evidence of linkage between schizophrenia and genetic markers located at these loci was found. A simulation study was carried out to gauge the significance of these results. The conclusions of a nonparametric linkage test (i.e., the affected pedigree member method) were equally negative. For each genetic marker, an allelic association with the disease was also sought: 80 unrelated patients and 80 healthy control subjects were tested, and no significant association was found. These results, which are in agreement with those obtained by other groups, do not support the involvement of the dopamine D1, D2, and D4 receptor genes in the pathogenesis of schizophrenia.

Failure to find evidence for linkage or association between the dopamine D3 receptor gene and schizophrenia.

OBJECTIVE: This study was performed to assess the possible involvement of the dopamine D3 receptor gene (DRD3) in the etiology of schizophrenia. The authors' approach included a population study and a family study using both parametric (lod score) and nonparametric (affected pedigree member) methods of linkage analysis. METHOD: Two different DNA markers were studied at the DRD3 locus. The family study included 35 multiplex families of schizophrenic subjects for the linkage analyses. The population study involved 50 unrelated schizophrenic subjects and 50 normal comparison subjects from the same ethnic and geographic origin. RESULTS: Whichever clinical classification was used to define the pathological phenotype (schizophrenia or schizophrenia spectrum), the results of the lod score and affected pedigree member studies did not provide any evidence of linkage of the DRD3 gene to the illness. The negative results of the association study reinforce these results. CONCLUSIONS: The hypothesis that the DRD3 gene has a predisposing role in schizophrenia was not supported by these population and family studies. However, the possibility that this gene has a role in the etiology of the disease cannot be definitely excluded because of the intrinsic limitations of the methods of analysis and the number of subjects studied.