scholarly journals Genomics, Transcriptomics and Methylomics: Alternative Approaches for the Analysis of Serotonin System and Antipsychotic Response

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
V. De Luca ◽  
R. De Souza ◽  
E. Viggiano ◽  
J. Volavka ◽  
J. Lieberman ◽  
...  

Serotonin receptors blockade is the major basis for the action of atypical antipsychotic drugs. Genetic factors affecting the density and/or function of serotonergic receptors, transporters and enzymes may therefore affect antipsychotic response. This exploratory study investigates the effect of ten polymorphisms from HTR1A, HTR1D, HTR2A, HTR3A, HTR3B, HTR4, HTR6, SLC6A4, TPH1, TPH2 genes on antipsychotic response in a sample of 289 patients with DSM-diagnosis of schizophrenia. Clinical Response was assessed using Brief Psychiatric Rating Scale (BPRS). Response was determined as 20% reduction improvement of BPRS compared to baseline. Selection of the biological relevant interactions, regardless the phenotype was performed using different statistics strategies regardless the phenotype to investigate epistasis within the serotonin system. the test for relevant interaction selection showed that 5HT4 and 5HT6 can be in epistatic relationship. the single locus analysis of these two receptor polymorphisms showed no significant results and the logistic regression model incorporating both genes, the clinical and demographic variables was not significant. Even this result is not significant, this strategy aimed to investigate the epistatic effect among genes could be useful for finding relevant biological interaction among genetic variants. Furthermore we are currently analyzing the methylation level of HTR2A in responders and non-responders, this epigenetic analysis will be very valuable in adding more information to the classic pharmacogenetic studies.

2008 ◽  
Vol 13 (6) ◽  
pp. 8-8
Author(s):  
Richard T. Katz

Abstract The author, who is the editor of the Mental and Behavioral Disorders chapter of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, comments on the previous article, Assessing Mental and Behavioral Disorder Impairment: Overview of Sixth Edition Approaches in this issue of The Guides Newsletter. The new Mental and Behavioral Disorders (M&BD) chapter, like others in the AMA Guides, is a consensus opinion of many authors and thus reflects diverse points of view. Psychiatrists and psychologists continue to struggle with diagnostic taxonomies within the Diagnostic and Statistical Manual of Mental Disorders, but anxiety, depression, and psychosis are three unequivocal areas of mental illness for which the sixth edition of the AMA Guides provides M&BD impairment rating. Two particular challenges faced the authors of the chapter: how could M&BD disorders be rated (and yet avoid an onslaught of attorney requests for an M&BD rating in conjunction with every physical impairment), and what should be the maximal impairment rating for a mental illness. The sixth edition uses three scales—the Psychiatric Impairment Rating Scale, the Global Assessment of Function, and the Brief Psychiatric Rating Scale—after careful review of a wide variety of indices. The AMA Guides remains a work in progress, but the authors of the M&BD chapter have taken an important step toward providing a reasonable method for estimating impairment.


1987 ◽  
Vol 2 (3) ◽  
pp. 174-187
Author(s):  
Monique de Bonis ◽  
Paul de Boeck ◽  
Marie-Odile Lebeaux

RésuméLe présent travail comporte une critique de la méthodologie employée pour définir une typologie des schizophrènes et une étude empirique de la distinction entre forme productive et forme déficitaire.Après avoir souligné que les études factorielles visant l’identification de deux types de schizophrènes reposaient sur des choix méthodologiques discutables: recherche de corrélations entre variables, alors qu’il s’agit de découvrir des corrélations entre sujets; préférence pour des relations symétriques, alors que les liaisons sont probablement d’ordre asymétrique, les auteurs présentent deux études empiriques.La première réalisée sur un échantillon de 99 schizophrènes s’appuie sur la factorisation des estimations de la symptomatologie (BPRS* á 42 items) à l’aide de la méthode factorielle en plan Q et d’une analyse des correspondances. La seconde a porté sur un sous-échantillon de 52 schizophrènes à l’aide d’une nouvelle méthode d’analyse hiérarchique (HICLAS). Les résultats de ces analyses aboutissent aux conclusions suivantes. Les résultats des analyses factorielles montrent: • qu’il existe plus de deux formes de schizophrènie et qu’à l’intérieur des classes formées par les individus l’opposition déficitaire -productif est stable quelle que soit la métrique utilisée; • que cette opposition repose principalement, pour ce qui est de la forme déficitaire sur 3 symptômes: l’émoussement affectif, le retrait affectif et le ralentissement, et pour ce qui est de la forme productive sur l’humeur expansive, l’attitude manipulatoire, l’excitation, la dramatisation et la labilit émotionnelle; • que contrairement aux travaux antérieurs ni les hallucinations ni la désorganisation conceptuelle ne permettent d’établir la différence entre les deux groupes de malades sans doute parce qu’elles sont communes à tous les schizophrènes; • qu’il n’y a pas de correspondance entre les diagnostics cliniques et les formes décrites; et, • que les malades les plus déficitaires (situés aux extrêmités du pole factoriel) se différencient des malades productifs essentiellement par des variables liées au sexe (plus d’hommes que de femmes dans le premier cas), un statut marital de célibat plus fréquent, et des antécédents psychiatriques plus importants. Les résultats des analyses factorielles soulignent d’une part que les types mixtes sont plus fréquents que les types purs et, d’autre part qu’il suffit de moins de 10 symptômes pour réaliser une opposition satisfaisante entre forme productive et forme déficitaire (Tableau 3, figure 1).Toutes ces conclusions sont valables aussi pour l’analyse hiérarchique. Mais de plus, cette méthode permet d’individualiser un groupe de malades “purs” dans la forme déficitaire seulement, groupe disjoint des autres individus sur la base d’un très petit nombre de symptômes. A côté de ces types purs figurent des types mixtes, qui possédent à la fois des symptômes déficitaires et des symptômes productifs suivant des combinaisons hiérarchiques précises, c’est-à-dire avec une dominance de l’une ou de l’autre forme. Il existe aussi des formes résiduelles dans lesquelles aucune hiérarchie ne peut être mise au jour (Tableau 4).En conclusion on a insisté, outre les problèmes méthodologiques négligés dans les précédentes recherches, sur l’existence d’une dissymétrie entre la forme déficitaire et la forme productive, dans la mesure où c’est seulement la forme déficitaire qui présente une grande singularité et sur l’importance des symptômes liés à la vie affective et à son appauvrissement qui ont un pouvoir discriminatif plus élevé que les symptômes productifs.*BPRS = Brief Psychiatric Rating Scale


1993 ◽  
Vol 38 (8) ◽  
pp. 534-540 ◽  
Author(s):  
Marie-A. Gagné ◽  
Hugues Cormier ◽  
Gérard Leblanc ◽  
Daniel Lévesque ◽  
Thérèse Di Paolo

A radioreceptor assay (RRA) was used to determine the neuroleptic plasma levels of 32 outpatients with schizophrenia receiving a high dose of neuroleptics (the equivalent of 18 mg or more of oral haloperidol per day) and undergoing a 50% partial and progressive reduction (ten percent each month for five months) in their medication. Plasma levels of neuroleptics were measured three times: before (T1) and immediately after the 50% reduction (T2) and five months later (T3). A linear correlation was observed between neuroleptic plasma levels obtained by RRA and the neuroleptic doses prescribed at T1 and T3. Furthermore, neuroleptic plasma levels were significantly lower at T3 than at T1. Concurrent evaluations of psychopathology were done using the Brief Psychiatric Rating Scale, and the results indicated that no correlation exists between neuroleptic plasma levels and the total rating scale scores at T1 but a significant correlation was observed at T3.


1994 ◽  
Vol 39 (4) ◽  
pp. 223-229 ◽  
Author(s):  
Gérard Leblanc ◽  
Hugues Cormier ◽  
Marie-Andrée Gagné ◽  
Sylvie Vaillancourt

This paper presents an open study which evaluated the clinical effects of a partial and progressive reduction in neuroleptic medication in 32 outpatients suffering from schizophrenia who were receiving high doses (equivalent of ≥ 18 mg of oral haloperidol per day; EHL). After an observation period of twelve weeks, each subject's dose of neuroleptics was reduced by 50% at the rate of 10% every four weeks. Patients were receiving a mean of 62 mg per day EHL at the beginning of the study and 30 mg per day EHL at the completion of the study. After the reduction, the following was observed: 1. a significant but modest change in psychopathology: a decrease in negative symptoms and in the total score on Brief Psychiatric Rating Scale; and 2. a significant increase in tardive dyskinesia symptoms. Six subjects relapsed but five of them recovered without increasing their reduced medication. Results of this study are discussed in the context of trying to find a minimal maintenance dose in the treatment of schizophrenia. The relative paucity of change despite a large reduction in medication argues for réévaluation of dosage in patients on high or very high doses of neuroleptics. The results suggest that many patients taking high doses could be maintained on significantly lower doses of neuroleptics. With gradual reduction of medication it would seem that many patients who are receiving a high dose of neuroleptic can achieve a lower dose than their current maintenance level.


1987 ◽  
Vol 151 (2) ◽  
pp. 152-155 ◽  
Author(s):  
K. R. Abraham ◽  
P. Kulhara

The efficacy of ECT was investigated in a double-blind trial. Twenty-two patients with schizophrenia received trifluoperazine and were randomly allocated to receive eight real or eight simulated ECTs. In the first eight weeks, the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale. However, the groups showed no significant differences from the twelfth week onwards. The superiority of real ECT was not confirmed at the end of six months.


1989 ◽  
Vol 22 (2-3) ◽  
pp. 168-176 ◽  
Author(s):  
J. Andersen ◽  
J.K. Larsen ◽  
V. Schultz ◽  
B.M. Nielsen ◽  
A. Kørner ◽  
...  

1997 ◽  
Vol 21 (11) ◽  
pp. 692-694 ◽  
Author(s):  
A. Thomas ◽  
G. Katsabouris ◽  
N. Bouras

This exploratory study assessed staff perceptions to the reduction of maintenance neuroleptic medication in patients with chronic schizophrenia living in a long-stay hospital. Ten in-patients were assessed at regular times over six months. In addition to the Brief Psychiatric Rating Scale (BPRS), data were obtained from nursing staff on patients' ward behaviour (Ward Behaviour Interview Schedule, WBIS), clinical global opinion (CGI) and staff reaction (SR) to the reduction of medication plan. The average decrease of BPRS and WBIS was not related to keyworker's clinical global impression. The SR increased against the reduction of medication over the study period (P<0.05). Staff perceptions in the treatment of patients with chronic schizophrenia and their possible influence on prescribed closes should be taken into consideration in addition to psychopathology and clinical symptoms.


Author(s):  
Ali N. Yashin ◽  
Dolly Roy ◽  
Prosenjit Ghosh

Background: Schizophrenia is one of the most commonly encountered psychiatric disorders. It is characterized by impairment in perception or expression of reality, leading to occupational and social dysfunction. Now a day’s mainstay of treatment of schizophrenia is by using atypical antipsychotics. Amisulpride and olanzapine are atypical antipsychotics which are commonly used in treatment of schizophrenia. The current study is undertaken to assess the efficacy of amisulpride which is a relatively newer antipsychotics against existing antipsychotic olanzapine.Methods: This was designed as a single-blind, prospective, parallel-group, observational study. Eighty adult patients of either sex were randomized to receive standard doses of the two drugs orally for 12 weeks, with follow up at 4 and 8 weeks. Effectiveness was assessed by change in the score of Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) score during the treatment period. Data were entered in Microsoft excel and statistical analysis were done using graph pad and p value <0.05 considered to be statistically significant.Results: Out of 80 adults patients 76 patients were evaluated by dividing into two groups, 38 patients were included in each group. Final BPRS score was less for olanzapine as compared to amisulpride (p<0.001). Improvement in CGI score is more in olanzapine group than amisulpride group which became statistically significant from 8th weeks onwards.Conclusions: Both amisulpride and olanzapine are very effective in controlling the symptoms of schizophrenia which is evident by significant decrease in BPRS, CGI-S and CGI-I score, but efficacy of amisulpride is still inferior to olanzapine.


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