RESUMO
OBJECTIVE: The γ-aminobutyric acid type A (GABA A) system may be implicated in obsessive-compulsive disorder, based on its major role in modulation of anxiety and its function as the principal inhibitory neurotransmitter system in the cortex. In addition, glutamatergic/GABAergic mechanisms appear to play a role in the pathophysiology of obsessive-compulsive disorder, making the GABA A receptor-γ2 (GABργ2) gene a good candidate for susceptibility in this disorder. METHOD: 118 probands meeting DSM-IV criteria for primary obsessive-compulsive disorder and their available parents were recruited for participation in this study and informed consent was obtained. An NciI restriction site polymorphism in the second intron was genotyped and data was analyzed using the Transmission Disequilibrium Test. RESULTS: In total, 61 of the participating families were informative (i.e., with at least one heterozygous parent). No biases were observed in the transmission of either of the two alleles (χ2 = 0.016, 1 d.f., p = 0.898) to the affected probands in the total sample. CONCLUSION/DISCUSSION: While these results do not provide support for a major role for the GABA A receptor-γ2 in obsessive-compulsive disorder, further investigations of this gene in larger samples are warranted.
OBJETIVO: O sistema gabaérgico tipo A (GABA A) pode estar implicado no transtorno obsessivo-compulsivo devido ao seu grande papel na modulação da ansiedade e da sua função como o principal neurotransmissor inibidor no córtex. Além disso, mecanismos glutamatérgicos/gabaérgicos parecem desempenhar um papel na fisiopatologia do transtorno obsessivo-compulsivo, tornando o gene do receptor GABA A-γ2 (GABRG2) um bom gene candidato para a suscetibilidade genética a este transtorno. MÉTODO: 118 probandos que preencheram os critérios do DSM-IV para transtorno obsessivo-compulsivo primário e seus pais (quando disponíveis) foram recrutados para a participação neste estudo; consentimento informado foi obtido. Um polimorfismo no sítio de restrição da enzima NciI, localizado no íntron 2, foi genotipado e os dados foram analisados utilizando-se o Teste de Desequilíbrio de Transmissão. RESULTADOS: No total, 61 das famílias participantes foram informativas (ou seja, com pelo menos um progenitor heterozigoto). Não foi observado desequilíbrio de transmissão de qualquer um dos dois alelos (χ2 = 0,016, 1 g.l., p = 0,898) aos probandos afetados. CONCLUSÃO/DISCUSSÃO: Apesar de estes resultados não fornecerem suporte para um papel importante para o gene GABA A-γ2 no transtorno obsessivo-compulsivo, novas investigações desse gene em amostras maiores são justificadas.
Assuntos
Adulto , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/genética , Receptores de GABA-A/genética , Manual Diagnóstico e Estatístico de Transtornos Mentais , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Desequilíbrio de Ligação , Polimorfismo GenéticoRESUMO
INTRODUCTION: An increasing amount of data suggests that dysregulation of the immune system, including the cytokine network, is associated with the etiology and pathophysiology of mood disorders. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. The aim of this study was to define the genetic immunologic scenario associated with major depressive disorder (MDD) and bipolar disorder. METHODS: Eighty-four Italian outpatients affected by bipolar disorder type I, bipolar disorder type II, or MDD, and 363 healthy controls were enrolled into the study. We analyzed allele and genotype distribution of -308 (G/A) tumor necrosis factor-a (TNF-a), +874 (T/A) interferon-g (IFN-g), -174 (G/C) interleukin (IL)-6, and -1082 (G/A) IL-10 promoter polymorphisms by Polymerase Chain Reaction Sequence Specific Primers technique. RESULTS: We observed different genotype and allele distributions of TNF-a, IFN-g, and IL-10 polymorphisms in the three groups of patients analyzed. In particular, bipolar II patients were characterized by an absence of adenine (A) high producer allele of TNF-a (P<.001) and a lower percentage of TT high producer genotype of IFN-g (P<.001); bipolar I individuals showed reduced percentage of AA low producer genotype of IL-10 (P<.001). Both bipolar I and bipolar II patients not carrying guanine (G) high producer IL-6 allele showed a lower mean age at onset (P=.048). CONCLUSION: These data support the existence of a genetic profile related to pro-inflammatory cytokines in patients affected by mood disorders. The differences observed across the three clinical phenotypes suggest the presence of different pathogenetic mechanisms involved in the susceptibility of phenotypically different mood disorders.