RESUMEN
BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP). METHODS: Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models. RESULTS: Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations. CONCLUSION: These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity.
Asunto(s)
Proteínas Asociadas a la Distrofina/genética , Alucinaciones/genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/genética , Adulto , Trastorno Bipolar/genética , Proteínas Portadoras/genética , Disbindina , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/genética , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: A variety of outcome measures are used in evaluating disease activity and therapeutic efficacy in rheumatoid arthritis (RA) studies, and this makes comparisons of drug efficacy difficult. Some of the endpoints used are not standardized and/or are insensitive to change. The purpose of this report is to present a critical appraisal of outcome measures and quality of life assessments in RA studies. METHOD: An overview of the literature was undertaken to determine the extent to which there is consensus among experts in this area of research. RESULTS: The data suggest that the core set of endpoints in RA clinical studies should include tender joint count swollen joint count, patients' assessment of pain, patients' and physicians' global assessments, patients' assessment of physical function and acute phase reactant level. When trials of disease-modifying antirheumatic drugs (DMARD) last for more than a year, radiography may be useful. A 'pooled index' may be valuable, and its construction is discussed. Quality of life (QoL) instruments facilitate a fuller examination of the effects of health care interventions and these should be used to complement the more traditional clinical endpoints in the core set. The instruments most commonly used in RA research are identified. CONCLUSIONS: We conclude that randomized clinical trials of treatments in RA should now ideally use the core set of clinical endpoints and validated QoL instruments for assessing safety and efficacy.
