Analysis of Community Participation in the 2020 Medan Mayor Election During the Covid-19 Pandemic

The purpose of this study was to analyze community participation and the factors that led to the non-achievement of the national target in the 2020 Medan City Regional Head election. The method used is qualitative-descriptive research, namely by presenting the facts found in a comprehensive manner through in-depth analysis. While the data analysis technique consists of data reduction, data presentation and conclusion drawing. The results of the research obtained are that in the 2020 Medan Mayor election, the number of community participation increased and increased compared to previous years, but still the national target for political participation was not achieved. The popularity of candidates is an important aspect of increasing public participation in the 2020 Medan elections. The existence of candidates seems to have a curious effect on the people of Medan City. In addition, the results of the study also concluded that the factors that caused the national target for the 2020 regional elections in Medan were not achieved, namely the ambiguity of government policies. On the one hand, the Government wants Covid-19 to be completed immediately with various policies such as social distancing and avoiding crowds, but it is still like forcing the 2020 Regional Head Election which is one of the sources of crowds even though there are aspects of implementing health protocols

Corpus callosum area in patients with bipolar disorder with and without psychotic features: an international multicentre study

BACKGROUND: Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls. METHODS: We analyzed anatomic T(1) MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. RESULTS: We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. LIMITATIONS: We found small to medium effect sizes, and there was no calibration technique among the sites. CONCLUSION: Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD

Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.: HERV-W in schizophrenia and bipolar disorder

International audienceEpidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of severe psychotic disorders

PHARMACOGENETIQUE DE LA SCHIZOPHRENIE

Since the serendipitous discovery of typical antipsychotics in the treatment of schizophrenia, several molecules have been developed for their tolerance and a specific action. However, before any prescription of these molecules, in the spirit of the disorder, the concept of resistance to the treatment was evoked. Indeed, there is an inter-individual variation of response to antipsychotics in schizophrenic subjects that was described by specific scales of evaluation. It appears that clinical factors seem to contribute to the non response of treatment and they are not appreciated so well. Psychotics follow specific pathways and it is know that physiological and biochemical effects depend on factors. Thus, smoking habits, alcohol and diet have been described as factors influencing variability in drug response. While age, gender and genetic factors seem to contribute to the quality of therapeutic response. Evidence from family, twin and adoption studies clearly demonstrate the involvement of genetic factors in schizophrenia. Both linkage and association studies support this hypothesis. Although the results of such studies remain inconsistent regarding the heterogeneity of the disease. Refinement of the phenotype using the pharmacogenetic approach could thus be useful in the genetic studies of schizophrenia. Pharmacogenetic research claim to assess a possible interaction between the therapeutic targets of antispychotics and their specific mutations in candidate genes. High affinity of atypical antipsychotics for 5-HT2A receptors may explain their specific efficacy/tolerability profile compared to conventional antipsychotics. A number of reports have associated a silent 5-HT2A polymorphism (T102) with response to clozapine or risperidone. This polymorphism is in complete linkage disequilibrium with a -1438A/G polymorphism, located within the promoter region of the gene, with conflicting results. Phenotypical heterogeneity of schizophrenia might explain such discrepancies. For example, negative symptoms are known to reflect severity of illness and to restrain therapeutic response. On this basis, we re-assessed the possible influence of the −1438A/G polymorphism of the 5-HT2A receptor gene on the clinical efficacy of atypical antipsychotics with focus on several relevant dimensions. The A allele and the AA genotype of the −1438A/G polymorphism of the gene coding for the 5-HT2A receptor were not associated with therapeutic response to atypical antipsychotics in our sample. Furthermore, the AA genotype appeared to be associated with the SANS score, raising the possibility that negative symptoms in schizophrenia constitute a confounding factor between the 5-HT2A gene and atypical antipsychotic response. Traditionally, dopaminergic and serotoninergic sytems have been used as targets for antipsychotic therapy. Although, most available antipsychotics have a multitarget profile without any clear mechanism of action. Recently, atypical antispychotics have been found to display a wide range of affinities for several neurotransmitters. Neurobiological research suggest a significant role of the endocannabinoid system in schizophrenia vulnerability and also in the quality of response to antipsychotics. Epidemiology studies show that patients consume twice more of cannabis than the general population. An increase of the density of receptors is observed in the dorsolateral prefrontal cortex of schizophrenic post mortem samples. The CNR1 gene, that encodes the CB1 receptor, is located on chromosome 6q14-15, which has been considered as a susceptibility locus for schizophrenia. Recent progress in pharmacogenetics, evaluating the individual risk for antipsychotic refractoriness, has focused notably on the dopaminergic and serotoninergic systems. However, so far, these studies led to discrepant data. This led us to assess the possible influence of the 1359G/A polymorphism as a haplotype tagging SNP of the CNR1 gene, in comparison with three other SNPs covering 14kb across this gene, on the risk of schizophrenia and/or therapeutic response to atypical antipsychotics. We found no difference in 1359G/A polymorphism between patients and control subjects, and no relationships were noted between this polymorphism and any clinical parameter considered as potential intermediate factor. However, the G allele frequency was significantly higher among non-responsive vs responsive patients, with a dose effect of the G allele. In contrast, no association was found for three other genetic polymorphisms of the CNR1 gene. Pharmacogenetics may in future lead to individualized pharmacotherapy based on the specific genetic, environmental and demographic characteristics of each patient. Pharmacogenetics could thus increase the patient comfort in terms of both higher initial response rates and reduced propensity to developing debilitating side-effects.Depuis la découverte, fruit du hasard des neuroleptiques pour traiter la schizophrénie, de nombreuses molécules ont été développées pour une meilleure tolérance et une meilleure efficacité. Toutefois, bien avant la prescription de ces molécules, à l'essence même de la pathologie, le concept de résistance a été évoqué. La variabilité interindividuelle de réponse aux antipsychotiques des sujets schizophrènes a pu être ainsi conceptualisée grâce à des échelles spécifiques d'évaluation. Il apparait que ces sujets non répondeurs se caractérisent par une symptomatologie clinique plus bruyante qui n'est pas toujours évaluée de manière spécifique par ce type d'échelles. Les psychotropes empruntent des voies bien définies et il est reconnu que les effets physiologiques et biochimiques de ces substances sont soumis à certaines influences. Ainsi, le type d'alimentation, l'alcool et le tabac sont autant de facteurs extrinsèques influant la réponse aux traitements tandis que l'âge, le sexe, le poids ou d'autres facteurs physiopathologiques (incluant les facteurs héréditaires) sont d'importants facteurs intrinsèques. L'hypothèse d'un sous bassement génétique de la schizophrénie est étayé par plusieurs travaux comme les études épidémiologiques, de liaison génétique et des gènes candidats. Toutefois, l'hétérogénéité phénotypique de la maladie amène à des résultats variables. De fait, le cloisonnement phénotypique à la non réponse aux antipsychotiques chez les patients schizophrènes, pourrait être contributif à ce type d'approche. La pharmacogénétique se base sur les connaissances pharmacologiques des antipsychotiques et des gènes candidats des récepteurs cibles de ces molécules. Se basant sur l'hypothèse sérotoninergique de la schizophrénie et le tropisme préférentiel des antipsychotiques atypiques pour le récepteur sérotoninergique 5-HT2A, les premières études dans ce domaine ont testé la qualité de la réponse à la clozapine avec les polymorphismes T102C -1438A/G de la région promotrice et du gène du récepteur 5-HT2A. On peut toutefois noter l'inconsistance des résultats. L'hétérogénéité phénotypique de la maladie pourrait, au travers de symptômes cliniques, souligner ces différences. Par exemple, les symptômes négatifs dont la constance au cours de la maladie et l'association avec une moins bonne réponse thérapeutique sont reconnus. Notre hypothèse était que la disparité des résultats des études pharmacogénétiques testant le gène du récepteur 5-HT2A était liée à l'interférence des symptômes négatifs eux-mêmes sous influence génétique. Nous avons donc choisi de tester le polymorphisme -1438A/G de la région promotrice du gène codant pour le récepteur 5-HT2A et la réponse aux antipsychotiques, évaluant de manière parallèle les variables cliniques pouvant aggraver la réponse aux traitements. Dans ce premier travail, nous avons constaté que les sujets mauvais répondeurs se définissent surtout par la gravité des symptômes négatifs. Nous ne retrouvons pas d'association positive entre le polymorphisme génétique -1438A/G et la réponse aux antipsychotiques atypiques. Toutefois, l'allèle A et le génotype AA semblent être significativement associés à l'intensité des symptômes négatifs intervenant ainsi comme potentiel facteur confusionnant dans les études pharmacogénétiques testant le récepteur 5-HT2A. Les théories dopaminergiques et sérotoninergiques dans la schizophrénie ont été enrichies d'autres hypothèses pharmacologiques comme l'implication des systèmes adrénergiques, histaminiques, muscariniques ou cannabinoides. Plusieurs arguments permettaient d'envisager le gène du récepteur CB1 comme potentiellement impliqué dans la réponse médicamenteuse chez les patients schizophrènes. La plupart des études épidémiologiques montrent que les patients schizophrènes consomment jusqu'à deux fois plus de cannabis que dans la population générale. Les études post mortem réalisées chez les patients schizophrènes montrent une augmentation de la densité de ces récepteurs au niveau du cortex préfrontal dorsolatéral et cela de manière indépendante à la consommation récente de cannabis. La localisation cérébrale des récepteurs CB1, leur rôle interactif avec d'autres neurotransmetteurs en particulier la dopamine ou le glutamate ont permis d'envisager l'hypothèse endocannabinoide de la schizophrénie. Le gène du récepteur CB1 est localisé sur la région chromosomique 6q14-15, une région potentiellement impliquée dans la schizophrénie. Dans un second travail, nous avons analysé le polymorphisme 1359G/A du récepteur CB1 (étant donné sa caractéristique de tag-SNP) dans la réponse aux antipsychotiques. Parallèlement, nous avons choisi de tester trois autres polymorphismes couvrant environ 14kb du gène du CB1. Nous trouvons une association significative entre l'allèle G et la mauvaise réponse aux antipsychotiques mais pas d'association avec la maladie. Les travaux de recherche en pharmacogénétique semblent pertinents dans la prédiction de la qualité de la réponse aux traitements chez les patients schizophrènes. Dans la mesure où les mécanismes d'actions des antipsychotiques sont connus, il semble aisé de tester les gènes des récepteurs cibles dans la prédiction de la réponse médicamenteuse. Ce type d'approche pourrait être contributive comme outil complémentaire au psychiatre afin d'améliorer le confort des patients à travers une meilleure compliance

Le tabagisme dans la schizophrénie (un lien avec les hallucinations ? Une étude menée chez 100 patients)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pharmacogénétique de la schizophrenie

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

La folie à deux (revue de la littérature)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF