Assuntos
Antipsicóticos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Aripiprazol , Sítios de Ligação , Encéfalo/metabolismo , Dopamina/metabolismo , Humanos , Receptores de Dopamina D2/metabolismo , Esquizofrenia/metabolismoRESUMO
Psychiatric patients demonstrate varied responses to treatment. Consequently, treatment strategies are trial-and-error, which has a negative effect on prognosis and compliance. The aim of pharmacogenomic research is to enable customised drug treatment by identifying variations within multiple candidate genes (those encoding drug-targeted neurotransmitter receptors, transporters and metabolic enzymes) that are likely to confer the inter-individual differences in drug response and development of drug-induced side effects. Pharmacogenetic and pharmacogenomic research to date has identified genetic polymorphisms of dopamine (DA) and serotonin (5-HT) receptor subtypes, the serotonin transporter (5-HTT) and metabolic enzymes (cytochrome P450 [CYP] family) as important contributors to the variability in response to psychiatric drugs and the development of drug-induced side effects such as tardive dyskinesia and weight gain. It is anticipated that technological and methodological advances will provide further candidate genes and refine association analyses of existing candidates, enabling pharmacogenomic research to move towards future treatment regimes that are catered to the individual.
Assuntos
Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Farmacogenética/métodos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Genética Comportamental/métodos , Humanos , Transtornos Mentais/enzimologia , Polimorfismo Genético , Ácido Retinoico 4 HidroxilaseRESUMO
A dysfunctional glutamatergic system has been implicated in the pathophysiology of schizophrenia. The group III metabotropic glutamate receptor (mGluR) types 7 and 8 presynaptically inhibit glutamate release, thereby modulating glutamatergic transmission in the brain. We conducted association studies to investigate the novel Tyr433Phe (mGluR7) variant and the 2846-C/T (mGluR8) polymorphism in schizophrenia. Both variants, present at high frequencies, failed to demonstrate any significant association with schizophrenia (mGluR7 [Tyr433Phe] allele: P=0.33; genotype: P=0.63; mGluR8 [2846-C/T] allele: P=0.72; genotype: P=0.63).
Assuntos
Polimorfismo Genético/genética , Receptores de Glutamato Metabotrópico/genética , Esquizofrenia/genética , Adulto , Alelos , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Esquizofrenia/diagnósticoAssuntos
Antipsicóticos/uso terapêutico , Proteínas de Transporte/genética , Clozapina/uso terapêutico , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Humanos , Repetições Minissatélites , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina , Reino Unido , População BrancaRESUMO
The adrenergic system plays an important role in psychiatric disorders such as depression and schizophrenia. Antagonism of the adrenergic receptor subtypes alpha1A and alpha2A has been found to have an antipsychotic effect. Genetic mutations in these receptors could be related to the alterations in the adrenergic system observed in psychiatric patients and to failure to respond to drug antagonism. We have studied one polymorphism in the alpha1A-adrenergic receptor (Arg492Cys) and two polymorphisms in the promoter region of the alpha2A-adrenergic receptor (-1291-C/G and -261-G/A) in a sample of clozapine-treated schizophrenic patients and controls. No clear differences were observed between the different groups suggesting that these polymorphisms did not play an important role in the aetiology of the disorder or in determining antipsychotic response.
