Search

Resume L’objectif de cette etude etait d’evaluer la frequence des temperaments affectifs, selon les criteres elabores par Akiskal et Mallya, sur une population de temoins sans antecedent personnel de trouble de l’humeur. En effet, ces temperaments ont ete largement etudies sur des cohortes de patients, mais on dispose de peu de donnees sur les populations de controles et les sujets a risque pour les troubles de l’humeur. Nous avons recrute et interviewe a l’aide du SCAN 185 sujets. Vingt ont ete exclus pour leurs antecedents familiaux de psychose schizophrenique (n = 1), leurs antecedents personnels de trouble thymique (n = 7) ou pour leur temperament cyclothymique (n = 12). Les 165 sujets restants ont ete divises en 3 groupes controles : dans le premier (AFN, n = 99), aucun ne presentait de pathologie psychiatrique familiale ; dans le second (AFP, n = 33), tous avaient des antecedents familiaux de trouble thymique au 1 er ou 2 e degre ; le troisieme (FBP, n = 33) etait compose de sujets recrutes dans la fratrie de patients bipolaires type I, selon les criteres du DSM IV. Aucun de ces temoins ne presentait de temperament cyclothymique. A chacun de ces sujets, nous avons fait passer un interview semi-structure pour les temperaments hyperthymique, depressif et irritable. Nos resultats mettent en evidence une frequence de deregulation temperamentale plus importante et statistiquement significative chez les sujets a risque (AFP et FBP) compares aux temoins, indemnes de pathologie familiale (AFN). En effet, les scores moyens obtenus pour les 3 echelles, ainsi que le Z-score (moyenne + 2 sd), differencient les sous-groupes de temoins entre eux. De plus, le pattern d’anomalie temperamentale ne semble pas identique dans les 2 groupes de temoins, avec antecedent familial et fratrie de bipolaires. En effet, le temperament est preferentiellement de type depressif chez les individus avec antecedent familial de trouble thymique. Au contraire, ces deregulations temperamentales sont plus heterogenes dans la fratrie des patients bipolaires, chez lesquels on retrouve, a la fois, une frequence importante de temperaments hyperthymique ou depressif. Ces resultats sont discutes en fonction des donnees de la litterature. Mais s’ils se confirmaient, ils pourraient temoigner en faveur d’une agregation familiale de ces anomalies chez les sujets a risque et accrediteraient la these d’une pathologie affective sub-syndromique, en marge des episodes affectifs majeurs. L’etude des temperaments ouvre ainsi la possibilite d’un nouveau paradigme de recherche pour les etudes biologiques, en general, et genetiques, en particulier.

The purpose of this study was to examine whether biological variables, such as erythrocyte membrane transports and plasma levels of monoamine precursor amino acids (tyrosine, tryptophan and phenylalanine), exhibit a particular pattern relatively to DSM-III depressive subgroups (dysthymic disorders, major recurrent depression and biopolar depression), when they are treated synthetically by a stepwise discriminant analysis. We conducted two tests in 97 subjects (64 depressed patients vs. 33 controls): the first before any antidepressant treatment, and the second after pharmacotherapy and clinical improvement. Our results clearly indicate a satisfying homogeneity for the controls and bipolar depressed patients as opposed to dysthymic disorders and major recurrent depression in both tests. The most informative biological variables are the erythrocyte membrane transports before treatment, tryptophan parameters after clinical improvement. Evidence is provided that multivariate analysis constitutes an interesting approach in biological psychiatry.

In a population-based association study, we tested the hypothesis that allelic variants of the human serotonin transporter (5-HTT) gene confer susceptibility to mood disorders. Both a biallelic repeat polymorphism in the 5′ promotor region that differentially modulates gene expression and a second intron variable-number-tandem-repeat (VNTR) marker were genotyped in 294 controls and 115 patients with mood disorders. Subjects were of West European descent and included 36 patients with major depressive disorder (MDD) and 79 patients with bipolar I disorder (BD). No significant differences in genotype or allele frequencies were found at either locus between controls and combined patients, nor between controls and MDD or BD patients separately. Thus, our data do not support the association between depressive disorder and a nine-repeat allelic variant of the 5-HTT VNTR marker recently reported by Ogilvie et al. (Lancet 347:731–733, 1996). More importantly, no association between alleles conveying functional differences in 5-HTT gene expression and MDD or BD could be found. Taken together, our data suggest that the 5-HTT gene is not commonly involved in the susceptibility to mood disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:1–3, 1998. © 1998 Wiley-Liss, Inc.

Since more than one century, the illness considerably evolved. Between the extremes of full-blown manic-depressive disorder and the strictly defined unipolar depression, patients exhibit particular affective conditions characterised by complex or soft symptoms. So the actual classification encompasses 6 clinical forms with sometimes, sub-forms. In this context, an awareness of the different clinical presentations is an important issue in the daily practice, especially hypomania, cyclothymia, mixed states and affective episode with delusion. These conditions are often misdiagnosed and the bipolar trouble is under-diagnosed. Although, the lifetime prevalence of the classical manic-depressive is about 1%, current evidences indicate that the bipolar spectrum account for 5-8% in the general population. So, the public health significance of a rapid and proper diagnosis is quite essential because the treatment needs to be applied in the clinical care.

Background: The modern concept of affective disorders focuses increasingly on the study of subthreshold conditions on the border of manic or depressive episodes. Indeed, a spectrum of affective conditions spanning from temperament to clinical episodes has been proposed by the senior author. As bipolar disorder is a familial illness, an examination of cyclothymic temperament (CT) in controls and relatives of bipolar patients is of major relevance. Methods: We recruited a total sample of 177 healthy symptom-free volunteers. These controls were divided into three groups. The first one is comprised of 100 normal subjects with a negative familial affective history (NFH); the second of 37 individuals, with positive affective family history (PFH); and a third of 40 subjects, with at least one sib or first-degree kin with bipolar disorder type I according to the DSM-IV (BPR). The last two groups defined at risk individuals. We interviewed all subjects with CT, as described by the senior author. Results: We found a statistically significant difference in the rates of CT between the subjects in BPR versus others. CT was also more prevalent in the PFH compared with NFH. Additionally, the simple numeration of the CT traits exhibited gradation in the distribution of individuals inside the NFH, PFH and BPR. Finally, categorically defined CT and CT traits predominated in females. Limitation and conclusion: Although not all relatives of bipolar probands were studied, our results exhibit an aggregation of CT in families with affective disorder—and more specifically those with bipolar background. These results allow us to propose the importance of including CT for phenotypic characterization of bipolar disorder. Furthermore, our results support a spectrum concept of bipolar disorder, whereby CT is distributed in ascending order in the well-relatives of those with depressive and bipolar disorders. We submit that this temperament represents a behavioral endophenotype, serving as a link between molecular and behavioral genetics.

Mutations in various ion channel genes are responsible for neuromuscular and other neurological disorders. We have previously identified the human small conductance calcium-activated potassium channel gene (hSKCa3) which has two tandemly arranged CAG repeats in its 5' region. Here we have isolated the first genomic clones containing the gene and have shown that both repeats are in exon 1. Homology to the previously localized sequence tagged site G16005 indicated that the gene may be on chromosome 22q, however using polymerase chain reaction amplification of somatic cell hybrid DNA and fluorescence in situ hybridization of two P1 artificial chromosome clones, we physically localized the gene to chromosome 1q21.3. We previously found an association between the highly polymorphic second (more 3') CAG repeat and schizophrenia in 98 patients and 117 controls. We have now genotyped an additional 19 patients with schizophrenia and have performed statistical analyses on the entire group of patients and controls to investigate the possible effect of age of onset, family history, and gender of the patients on the observed association. None of these factors were found to influence the results. Both CAG repeats have been typed in 86 bipolar I disorder patients, and no significant difference in allele distribution was observed between our bipolar disorder patients and controls.

International audience; The XNP/ATR-X gene is involved in several X-linked mental retardation phenotypes: the ATR-X syndrome, the Juberg-Marsidi syndrome, and some severe mental retardation phenotypes without alpha-thalassemia. Using a vectorette strategy, we have identified and sequenced the intron/exon boundaries of this gene. The gene is composed of 35 exons. It encodes a potential protein of 2492 amino acids. A search of the databases identified three zinc finger motifs within the 5' end of the gene. Expression analysis in different tissues indicated that an alternative splicing event that involves exon 6 is occurring. One of these alternatively spliced transcripts is predominantly expressed in embryonic tissues. These data led us to search for mutations in the 5' region in ATRX patients without other mutations in the 3' region. In one patient a mutation was found in which part of exon 7 was removed from the XNP transcript, as a result of a mutation creating a novel splice site that is substituted for the natural splice site. This new splicing event removed one zinc finger motif. This is the first example of a mutation in XNP within the 5' coding region. It suggests that mutations will be predominantly found in the helicase region as well as in the zinc finger regions and leads us to propose a large screening of additional patients.

A dual CO(2) laser-based differential absorption lidar (DIAL) system has been constructed and demonstrated for range-resolved mapping of chemical vapor plumes. The system acquires high range resolution through the use of plasma-shutter pulse clippers that extinguish the nitrogen tail of the CO(2)-laser output. Aprogrammable servomotor-driven scanner allows full hemispherical coverage of the interrogated field. A high-speed direct-detection receiver subsystem is used to gather, process, and display vapor-concentration data in near real time. Data demonstrating range-resolved detection of low concentrations of chemical plumes from ranges of 1 to 2 km are presented. In the column-content detection mode, trace levels of secondary vapors from various organophosphate liquids were monitored. Detection of an SF(6) vapor plume released 16 km from the DIAL system is also adduced.