Asunto(s)
Enfermedad de Graves/complicaciones , Heterotopia Nodular Periventricular/complicaciones , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/etiología , Adulto , Antipsicóticos/uso terapéutico , Antitiroideos/uso terapéutico , Benzodiazepinas/uso terapéutico , Femenino , Enfermedad de Graves/tratamiento farmacológico , Humanos , Metimazol/uso terapéutico , Olanzapina , Heterotopia Nodular Periventricular/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológicoRESUMEN
Recent progress in genotyping technology and the development of public databases has enabled large-scale genome-wide association tests with diseases. We performed a two-stage genome-wide association study (GWAS) of bipolar disorder (BD) in Japanese cohorts. First we used Affymetrix 100K GeneChip arrays in the analysis of 107 cases with bipolar I disorder and 107 controls, and selected markers that were nominally significant (P < 0.01) in at least one of the three models (1,577 markers in total). In the follow-up stage, we analyzed these markers using an Illumina platform (1,526 markers; 51 markers were not designable for the platform) and an independent sample set, which consisted of 395 cases (bipolar I + II) and 409 controls. We also assessed the population stratification of current samples using principal components analysis. After the two-stage analysis, 89 markers remained nominally significant (allelic P < 0.05) with the same allele being consistently over-represented in both the first and the follow-up stages. However, none of these were significant after correction for multiple-testing by false discovery rates. Sample stratification was virtually negligible. Collectively, this is the first GWAS of BD in the Japanese population. But given the small sample size and the limited genomic coverage, these results should be taken as preliminary.
Asunto(s)
Trastorno Bipolar/genética , Estudio de Asociación del Genoma Completo/métodos , Adulto , Anciano , Pueblo Asiatico/genética , Trastorno Bipolar/epidemiología , Estudios de Casos y Controles , Femenino , Marcadores Genéticos , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Proyectos Piloto , Análisis de Componente PrincipalRESUMEN
Methamphetamine, a potent psychostimulant, may cause a condition of mood disorder among users. However, arguments concerning methamphetamine-induced mood disorder remain insufficient. This case study describes a male with methamphetamine-induced bipolar disorder not accompanied by psychotic symptoms, who twice in an 11-year treatment period, manifested an ultra-rapid cycler condition alternating between manic and depressive mood states with 3- to 7-day durations for each. The conditions ensued after a bout of high-dose methamphetamine use and shifted to a moderately depressive condition within 1 month after the use under a treatment regimen of aripiprazole and mood stabilizers. The cycler condition may be characteristic of a type of the bipolar disorder and a sign usable for characterization. Further efforts are needed to seek distinctive features and to improve diagnostic assessment of methamphetamine-induced mood disorders.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Procesamiento de Imagen Asistido por Computador , Tamizaje Masivo/métodos , Anciano , Anciano de 80 o más Años , Atrofia/diagnóstico , Diagnóstico Diferencial , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Curva ROC , Estudios RetrospectivosRESUMEN
Based on the neurodevelopmental hypothesis in the etiology of schizophrenia, neurotrophic factors may be involved in the pathogenesis of the illness. We searched for polymorphisms in the promoter region of the neurotrophin-3 (NTF3) gene by using denaturing high performance liquid chromatography (DHPLC). Six single nucleotide polymorphisms (SNPs) were found. When these polymorphisms were examined for association with schizophrenia, a weakly significant difference was observed in the genotype distribution of the G/- 3004/A polymorphism between 184 schizophrenics and 185 controls (P < 0.05), although no statistically significant association was detected in a family-based sample of 50 trios (schizophrenics and their parents). With respect to the other polymorphisms, there was no significant association with schizophrenia. The G/- 3004/A polymorphism was in linkage disequilibrium with the CA repeat polymorphism in the first intron of the NTF3 gene. When haplotype-based analysis was performed, an increased frequency of the haplotype containing the G(- 3004) and the "A3" ([CA]23) alleles was observed for the schizophrenics compared to controls. Our results suggest that the G(- 3004)-A3 haplotype has a modest effect of giving susceptibility to schizophrenia.
Asunto(s)
Neurotrofina 3/genética , Regiones Promotoras Genéticas/genética , Esquizofrenia/genética , Adulto , Anciano , Alelos , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
Several lines of evidence suggest a possible role for reelin in the pathogenesis of neurodevelopmental diseases, particularly schizophrenia. Genes encoding reelin and proteins involved in the signal pathway of reelin are thus candidate genes for schizophrenia. We examined the polymorphic CGG repeat in the 5'-untranslated region (UTR) of the reelin gene, which was recently found to be associated with autistic disorder, and the CGG repeat in the 5' UTR region of the very low density protein receptor (VLDLR) gene, which was reported to be associated with sporadic Alzheimer's disease, for allelic association with schizophrenia. The subjects consisted of 150 patients and 150 controls matched for sex, age and ethnicity (Japanese). We found no significant association of schizophrenia with the trinucleotide repeat polymorphism of the reelin or VLDLR genes, suggesting that these polymorphisms do not have a major role in the pathogenesis of the disease.
Asunto(s)
Región de Flanqueo 5'/genética , Moléculas de Adhesión Celular Neuronal/genética , Proteínas de la Matriz Extracelular/genética , Receptores de LDL/genética , Esquizofrenia/genética , Repeticiones de Trinucleótidos/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Japón , Desequilibrio de Ligamiento , Masculino , Proteínas del Tejido Nervioso/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Proteína Reelina , Factores de Riesgo , Análisis de Secuencia de ADN , Serina EndopeptidasasRESUMEN
Reelin is a protein which plays an important role in cell construction and proliferation of neurons during the development of the central nervous system. Several lines of evidence suggest a possible role for reelin-related genes in the etiology of neurodevelopmental as well as neurodegenerative diseases. It is possible that variations in reelin-related genes (Reelin, VLDLR, FYN, CNRs, a3b1INTEGRIN, mDAB1) may be involved in the pathogenesis of schizophrenia and Alzheimer's disease. We have been conducting a systematic survey of the association of reelin-related gene polymorphisms with these disorders. Previously, we examined the association of the triplet repeats of the reelin and VLDLR gene with schizophrenia. We found no significant association of schizophrenia with the trinucleotide repeat polymorphism of the reelin nor VLDLR genes (Akahane et al. 2002). In this study, we performed an allelic association analysis in Alzheimer's disease and schizophrenia with three polymorphisms of the fyn gene reported by Ishiguro et al (2000). Diagnosis was based on DSM-IV and NINCDS-ADRDA. We found no significant differences in genotype distribution or allelic frequency between patient and control groups. Thus, it is unlikely that these polymorphisms play an important role in the pathogenesis of Alzheimer's disease or schizophrenia.