RESUMEN
Although to date there have been no conclusive pathophysiological findings in support of the degenerative theory of the etiology of schizophrenia, the results of neuroimaging studies have suggested that progressive changes in the brain do occur during the clinical course of schizophrenia. However, there has been no report on alterations in regional cerebral blood flow (rCBF) under resting condition, which was compared between the first-episode and the chronic patients of schizophrenia and healthy controls. Therefore, in this study, we applied three-dimensional stereotactic surface projection analysis of resting SPECT (3D-SSP SPECT) in patients with first-episode (n=18) and chronic schizophrenia (n=23) and age-/sex-matched healthy controls (n=40). The rCBFs in the middle/inferior/medial frontal gyrus and the anterior cingulate gyrus were significantly decreased in both patient groups, relative to the respective controls (Z>3.0, P<0.001, uncorrected). The chronic group showed significant hypoperfused region in the left inferior parietal lobule and middle/inferior temporal gyrus. Furthermore, within-cases comparison between the first-episode and chronic schizophrenia, revealed that the significant hypoperfused regions in the chronic group, compared to the first-episode group, were not only the lateral and medial prefrontal cortex, but also the inferior parietal cortex, posterior part of the temporal lobe, and the cuneus. The present study suggested that the reduction in rCBF occurs in the posterior brain area in addition to the frontal lobe across all clinical stages of schizophrenia.
Asunto(s)
Encéfalo/patología , Circulación Cerebrovascular/fisiología , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Esquizofrenia/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto JovenRESUMEN
Accumulating evidence suggests that phosphatidylinositol (PI) pathways have been involved in the secretion of dopamine (DA) and the regulation of DA transporter, which is a target of methamphetamine (METH). A recent large-scale gene-association study in a Dutch population demonstrated that the PIK4CA gene was closely linked to schizophrenia [Jungerius et al. (2007); Mol Psychiatry]. Here, we conducted a case (N = 232)-control (N = 233) study of the PIK4CA gene on Japanese METH abusers, which can manifest severe psychosis similar to schizophrenia. The genotype and allelic distributions of all four single nucleotide polymorphisms (SNPs) did not differ significantly between the METH abusers and the controls. The comparisons based on the classification of the psychosis as transient or prolonged and on the presence or absence of spontaneous relapse revealed no significant distribution of the four SNPs compared to the controls. Furthermore, haplotype analyses showed almost the same frequencies between the METH abusers and the controls. The present study suggests that the PIK4CA gene does not play a significant role in the vulnerability to METH use disorder in the Japanese population.
Asunto(s)
Trastornos Relacionados con Anfetaminas/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Metanfetamina/efectos adversos , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Trastornos Psicóticos/genética , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Metanfetamina/administración & dosificación , Persona de Mediana Edad , Antígenos de Histocompatibilidad MenorAsunto(s)
Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Fluvoxamina/uso terapéutico , Receptores sigma/agonistas , Psicología del Esquizofrénico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto , Femenino , Humanos , Receptor Sigma-1RESUMEN
Accumulating evidence suggests that oxidative stress plays a role in the mechanisms of action of methamphetamine (METH) in the brain. In the present study, we investigated the association between the genetic polymorphisms among glutathione (GSH)-related enzymes; glutathione S-transferases (GSTs) such as GSTT1 (Non-deletion/Null), GSTT2 (Met139Ile), GSTA1 (-69C/T), and GSTO1 (Ala140Asp); glutathione peroxidase 1 (GPX1) (Pro198Leu); and glutamate-cysteine ligase modifier (GCLM) subunit and METH use disorder in a Japanese population. Two hundred eighteen METH abusers and 233 healthy controls were enrolled in the study. There was a significant difference in GSTT1 genotype frequency between patients with METH psychosis and controls (P = 0.039, odds ratio: 1.52, 95% CI 1.03-2.24). Furthermore, the frequency (66.0%) of the GSTT1 null genotype among prolonged-type METH psychotic patients with spontaneous relapse was significantly higher (P = 0.025, odds ratio: 2.43, 95% CI 1.13-5.23) than that (44.4%) of transient-type METH psychotic patients without spontaneous relapse. However, there were no associations between the polymorphisms of other genes and METH abuse. The present study suggests that the polymorphism of the GSTT1 gene might be a genetic risk factor of the development of METH psychosis in a Japanese population.
Asunto(s)
Trastornos Relacionados con Anfetaminas/genética , Glutatión Transferasa/genética , Metanfetamina , Polimorfismo Genético , Adulto , Anciano , Trastornos Relacionados con Anfetaminas/epidemiología , Estudios de Casos y Controles , Femenino , Glutatión Transferasa/fisiología , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , RecurrenciaRESUMEN
Obsessive-compulsive disorder (OCD) is considered to involve abnormalities in inhibitory processes including gating systems. Auditory P50 inhibition, which is assessed by using a paired auditory stimulus paradigm to record P50 mid-latency evoked potential, is assumed to reflect sensory gating. In the present study, we investigated auditory P50 inhibition in subjects with OCD, and examined the relationship between P50 and clinical variables or neuropsychological performance. Twenty-six subjects with OCD and 26 age- and sex-matched healthy controls received P50 recording and neuropsychological tests. In the OCD subjects, we also evaluated clinical features including OC symptoms and subtypes of the disorder. P50 T/C ratios were significantly higher in OCD subjects than in control subjects (t=2.9, df=50, p=0.006). Compared to the controls, the OCD subjects performed significantly worse on the Symbol Digit Modalities Test (SDMT) and the Trail Making Test (TMT). There were no correlations between P50 T/C ratios and clinical variables or the results of neuropsychological tests. Our findings suggest that sensory gating deficits may be involved in the pathophysiology of OCD in a different way from clinical symptoms and executive attention dysfunction.
Asunto(s)
Trastornos del Conocimiento/fisiopatología , Potenciales Evocados Auditivos/fisiología , Inhibición Psicológica , Trastorno Obsesivo Compulsivo/fisiopatología , Estimulación Acústica/métodos , Adulto , Estudios de Casos y Controles , Electroencefalografía , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: Protein interacting with C-kinase-1 (PICK1) plays a role in the targeting and clustering of dopamine transporter, which is the primary target site for the abused drug methamphetamine. Based on the interaction of PICK1 with dopamine transporter, it is of particular interest to investigate the association between the PICK1 gene and methamphetamine abusers. METHOD: The authors studied the association between PICK1 gene polymorphisms and methamphetamine abusers in a Japanese group. Two hundred and eight methamphetamine abusers and 218 healthy comparison subjects were enrolled in the study. Furthermore, the authors also examined the effects of single nucleotide polymorphisms (SNPs) in the promoter and 5'-untranslated region on transcription levels of PICK1. RESULTS: The authors identified four highly frequent SNPs, rs737622 (-332 C/G) and rs3026682 (-205 G/A) in the promoter region and rs713729 (T/A) in intron3 and rs2076369 (T/G) in intron4. Of these SNPs, rs713729 was significantly associated with methamphetamine abusers in general, and rs713729 and rs2076369 were significantly associated with those with spontaneous relapse of psychosis. Furthermore, haplotype analysis revealed that specific haplotypes of these SNPs were associated with methamphetamine abusers. A gene reporter assay revealed that the two SNPs in the promoter region significantly altered transcriptional activity. CONCLUSIONS: Our findings suggest that the PICK1 gene may be implicated in the susceptibility to spontaneous relapse of methamphetamine psychosis and that, as an intracellular adapter protein, PICK1 may play a role in the pathophysiology of methamphetamine psychosis.
Asunto(s)
Trastornos Relacionados con Anfetaminas/genética , Proteínas Portadoras/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas Nucleares/genética , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , Psicosis Inducidas por Sustancias/diagnóstico , Adolescente , Adulto , Anciano , Trastornos Relacionados con Anfetaminas/metabolismo , Pueblo Asiatico/genética , Proteínas Portadoras/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos/genética , Humanos , Inteínas/genética , Japón , Masculino , Metanfetamina/efectos adversos , Metanfetamina/metabolismo , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Pronóstico , Psicosis Inducidas por Sustancias/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Although preclinical studies suggest that methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propan-1-one) and 5-MeO-MIPT (5-methoxy-N-methyl,N-isopropyl tryptamine) may have psychostimulant properties, the scientific reports about the clinical effects of these agents are scant. We describe a 27-year-old male patient with substance intoxication after a single ingestion of the mixture of methylone and 5-MeO-MIPT. Though he bought the drug as pure methylone powder via an internet order, our chemical analyses indicated that the drug was composed of about 60% methylone (120 mg) and 38% 5-MeO-MIPT (76 mg). This case report suggests that clinicians should be alert to the possibility of the emergence of methylone or 5-MeO-MIPT intoxication, and substance-related mental disorder may be complicated by combined use of other psychoactive drugs.
Asunto(s)
Metanfetamina/análogos & derivados , Psicosis Inducidas por Sustancias/psicología , Trastornos Relacionados con Sustancias/psicología , Triptaminas/envenenamiento , Adulto , Acatisia Inducida por Medicamentos/psicología , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Metanfetamina/análisis , Metanfetamina/envenenamiento , Triptaminas/análisisRESUMEN
Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia.
Asunto(s)
Variación Genética/genética , Receptores sigma/genética , Esquizofrenia/genética , Adulto , Sustitución de Aminoácidos/genética , Estudios de Casos y Controles , Codón/genética , Exones/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Estadística como Asunto , Receptor Sigma-1RESUMEN
BACKGROUND: Sigma1 receptors are involved in the pathogenesis of drug abuse. Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1) have been identified. To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study. METHODS: We initially screened for polymorphisms in the 5'-upstream region. The effects of the polymorphisms on transcriptional activity were determined using a gene reporter assay. The distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302 control subjects. RESULTS: A novel T-485A polymorphism was identified. The transcriptional activity of the A-485 allele and the TT-241-240 allele was significantly reduced compared with that of the T-485 allele and the GC-241-240 allele. The frequencies of the A-485 allele (chi2=5.575, df=1, p=.0205) and the TT-241-240/Pro2 haplotype (chi2=21.464, df=1, p<.0001) were significantly higher in control subjects compared with alcoholic subjects. The T-485A and the GC-241-240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2 haplotype are possible protective factors for the development of alcoholism.
Asunto(s)
Alcoholismo/genética , Aldehído Deshidrogenasa/genética , Expresión Génica/genética , Polimorfismo Genético/genética , Receptores sigma/genética , Adulto , Alcoholismo/etnología , Alcoholismo/rehabilitación , Aldehído Deshidrogenasa Mitocondrial , Estudios de Casos y Controles , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos/genética , Hospitalización , Humanos , Japón , Masculino , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/epidemiología , Receptores sigma/fisiología , Índice de Severidad de la Enfermedad , Transcripción Genética , Receptor Sigma-1RESUMEN
UNLABELLED: Since delusional disorder is characterized by mono-symptomatic paranoid symptoms, it can be a good clinical model for investigating the dopaminergic mechanism responsible for paranoid symptoms. We examined neuroleptic responses, plasma homovanillic acid (pHVA) and genes of the dopamine receptor (DR) and its synthesizing enzyme (tyrosine hydroxylase: TH) in patients with delusional disorder and compared them with those of schizophrenic patients and healthy controls. RESULTS: (1) A relatively small dose of haloperidol was more effective for delusional disorder than for schizophrenia. (2) The pretreatment level of pHVA was higher in patients with persecution-type, but not in those with jealousy-type delusional disorder, compared with age- and sex-matched controls. This increased pHVA level was decreased eight weeks after successful haloperidol treatment. (3) The genotype frequency of the DRD2 gene Ser311Cys was significantly higher in patients with persecution-type delusional disorder (21%), compared with schizophrenic patients (6%) or controls (6%). (4) Patients homozygous for the DRD3 gene Ser9Ser had higher pretreatment levels of pHVA than those heterozygous for Ser9Gly. (v) A significant positive correlation was found between the polymorphic (TCAT)(n) repeat in the first intron of the TH gene and pretreatment levels of pHVA in delusional disorder. We suggest that delusional disorder, especially the persecution-type, includes a "dopamine psychosis," and that polymorphism of the DRD2, DRD3 and/or TH gene is part of the genetic basis underlying the hyperdopaminergic state that produces paranoid symptoms. Further studies on a large sample size are required.
Asunto(s)
Trastornos Psicóticos/genética , Receptores Dopaminérgicos/genética , Esquizofrenia Paranoide/genética , Adulto , Antipsicóticos/uso terapéutico , Femenino , Genotipo , Ácido Homovanílico/sangre , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/sangre , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/psicología , Esquizofrenia Paranoide/sangre , Esquizofrenia Paranoide/tratamiento farmacológico , Esquizofrenia Paranoide/psicologíaRESUMEN
In 1980s, abuse and dependence of BRON-W syrup (cough suppressant), which contains methylephedrine, dihydrocodeine, chlorpheniramine and caffeine, were prevalent in Japan. Pharmacological and clinical studies suggest that methylephedrine and dihydrocodeine cause dependence. Although BRON-L syrup, newly modified cough suppressant contains only chlorpheniramine and caffeine, there still are abuse and dependence of this drug. In this report, three cases of BRON-L syrup abuse are demonstrated. All cases started using BRON-L syrup in the late teens in their peer groups, and dropped out from school. Case 1 misused only BRON-L syrup, but case 2 and 3 were multi-drug abusers (case 2: amphetamine, cocaine, and marijuana, case 3: solvent, alcohol, bromovalerylurea), and had kept in tough with the peer groups. Case 2 and 3 hospitalized more than 2 times. Withdrawal symptoms, such as headache, insomnia, and irritability were mild and improved in a few weeks after drug use was stopped. These findings suggest that 1) psychosocial backgrounds of these cases are in common with those of BRON-W syrup abusers, but 2) the clinical course and prognosis of multi-drug abusers are different from the BRON single abuser, 3) chlorpheniramine and caffeine possibly cause dependence, 4) abusers are likely to choose BRON brand although two main dependence-producing constituents are removed from it now. Therefore, prevention and care of BRON-L abusers requires both psychosocial and pharmacological aspects.