RESUMO
OBJECTIVE: Variation in the serotonin transporter gene (SLC6A4) promoter region has been shown to influence depression in persons who have been exposed to a number of stressful life events. METHOD: We evaluated whether genetic variation in 5-HTTLPR, influences current depression, lifetime history of depression and quantitative measures of depression in persons with chronic psychotic disorders. This is an association study of a genetic variant with quantitative and categorical definitions of depression conducted in the southwest US, Mexico and Costa Rica. We analyzed 260 subjects with a history of psychosis, from a sample of 129 families. RESULTS: We found that persons carrying at least one short allele had a statistically significant increased lifetime risk for depressive syndromes (P < 0.02, odds ratio 2.18, 95% CI 1.10-4.20). CONCLUSION: The 'ss' or 'sl' genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of psychotic individuals to develop major depression during the course of their illness.
Assuntos
Transtorno Depressivo/genética , Polimorfismo Genético/genética , Transtornos Psicóticos/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Alelos , Doença Crônica , Comorbidade , Costa Rica/epidemiologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Masculino , México/epidemiologia , Razão de Chances , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Tempo , Estados Unidos/epidemiologiaRESUMO
Schizophrenia (SC) and bipolar disorder (BP) share many clinical features, among them psychosis. We previously identified a putative gene locus for psychosis on chromosome 18p in a sample from the Central Valley of Costa Rica (CVCR) population. The present study replicated the association to a specific allele of microsatellite marker D18S63 on 18p11.3, using a newly collected sample from the CVCR. A combined analysis of both samples, plus additional subjects, showed that this specific allele on D18S63, which lies within an intron on the TGFB-induced factor (TGIF) gene, is strongly associated (P-value=0.0005) with psychosis. Eleven additional SNP markers, spanning five genes in the region, were analyzed in the combined sample from the CVCR. Only the four SNPs within the TGIF gene were in strong linkage disequilibrium with D18S63 (D'=1.00). A specific haplotype for all five markers within the TGIF gene showed evidence of association (P-value=0.011) to psychosis. A second, distinct haplotype, containing a newly identified nonsynonymous polymorphism in exon 5 of the TGIF gene, showed a nonsignificant trend towards association to psychosis (P-value=0.077). TGIF is involved in neurodevelopment, neuron survival and controls the expression of dopamine receptors. Altogether, our results point to the possible involvement of TGIF in the pathophysiology of psychotic disorders in the CVCR population.
Assuntos
Cromossomos Humanos Par 18 , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Polimorfismo Conformacional de Fita Simples , Transtornos Psicóticos/genética , Proteínas Repressoras/genética , Alelos , Animais , Mapeamento Cromossômico , Costa Rica , Análise Mutacional de DNA , Saúde da Família , Feminino , Frequência do Gene , Humanos , Desequilíbrio de Ligação , MasculinoRESUMO
Schizophrenia is a complex psychiatric disorder, likely to be caused in part by multiple genes. In this study, linkage analyses were performed to identify chromosomal regions most likely to be associated with schizophrenia and psychosis in multiplex families of Mexican and Central American origin. Four hundred and fifty-nine individuals from 99 families, containing at least two siblings with hospital diagnoses of schizophrenia or schizoaffective disorder, were genotyped. Four hundred and four microsatellite markers were genotyped for all individuals and multipoint non-parametric linkage analyses were performed using broad (any psychosis) and narrow (schizophrenia and schizoaffective disorder) models. Under the broad model, three chromosomal regions (1pter-p36, 5q35, and 18p11) exhibited evidence of linkage with non-parametric lod (NPL) scores greater than 2.7 (equivalent to empirical P values of less than 0.001) with the peak multipoint NPL = 3.42 (empirical P value = 0.00003), meeting genomewide evidence for significant linkage in the 1pter-p36 region. Under the narrow model, the same three loci showed (non-significant) evidence of linkage. These linkage findings (1pter-p36, 18p11, and 5q35) highlight where genes for psychosis and schizophrenia are most likely to be found in persons of Mexican and Central American ancestry, and correspond to recent linkages of schizophrenia or psychosis in other populations which were formed in part from emigrants from the Spanish empire of the 15th and 16th centuries.
Assuntos
Predisposição Genética para Doença/genética , Genoma Humano/genética , Linhagem , Transtornos Psicóticos/genética , Esquizofrenia/genética , América Central/etnologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Ligação Genética , Humanos , México/etnologia , Fenótipo , Estatísticas não ParamétricasRESUMO
OBJECTIVE: This study used the population of the Central Valley of Costa Rica (CVCR) and phenotyping strategies alternative to DSMIV classifications to investigate the association of neuregulin 1 with schizophrenia. METHOD: Using 134 family trios with a history of psychosis, we genotyped six of the seven markers originally identified to be associated with schizophrenia in Iceland. RESULTS: The neuregulin Icelandic haplotype was not associated with schizophrenia in the CVCR population. However, a novel haplotype was found to be overrepresented in subjects with functional psychosis (global P-value > 0.05). Stratification of the sample by history of mania suggests that this haplotype may be preferentially over-transmitted to persons with a history of manic psychosis. CONCLUSION: These results suggest that the neuregulin 1 gene is unlikely to play a major role in predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings.
Assuntos
Transtorno Bipolar/etnologia , Transtorno Bipolar/genética , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Proteínas do Tecido Nervoso/genética , Esquizofrenia/etnologia , Esquizofrenia/genética , Área Programática de Saúde , Costa Rica/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Repetições de Microssatélites , Neuregulina-1 , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The purpose of this study was to assess ethnic differences in the negative symptom profile of 25 Anglo American and 26 Mexican American subjects with schizophrenia. Subjects were rated at the end of a 1-2-week medication washout period (time 1) and at discharge (time 2) with the Negative Symptoms Assessment (NSA), Brief Psychiatric Research Scale, (BPRS), the [Diagnostic and Statistical Manual of Mental Disorders (4th edition)] DSM-IV negative factor score and LAECA acculturation scale. Total NSA scores were significantly higher among Mexican Americans both at time 1 and time 2. Among the five subscales of the NSA, ethnic differences were significant only for the Cognition subscale at time 1. Results indicate no ethnic differences in core negative symptoms (alogia, avolition, flat affect), but do suggest that a cognition-related factor differs between Mexican American and Anglo American schizophrenic patients.