RESUMEN
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.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Trastorno Obsesivo Compulsivo/genética , Receptores de GABA-A/genética , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Desequilibrio de Ligamiento , Polimorfismo GenéticoRESUMEN
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 (chi² = 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.
Asunto(s)
Trastorno Obsesivo Compulsivo/genética , Receptores de GABA-A/genética , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Polimorfismo GenéticoRESUMEN
Post-traumatic stress disorder is a difficult to treat, yet common disorder, which is associated with significant morbidity, mortality and societal burden. Comprehensive management of post-traumatic stress disorder must include both psychotherapeutic and pharmacologic components. The current evidence-based pharmacologic management approaches to post-traumatic stress disorder, suggests that first-line treatments for monotherapy are the selective serotonin reuptake inhibitors, sertraline, paroxetine and fluoxetine. Other potential options include other monotherapies including venlafaxine, mirtazapine, tricyclic antidepressants, monoamine oxidase inhibitors, as well as adjunctive usage of atypical antipsychotics, lamotrigine, trazadone and a number of adrenergic agents. A trial of therapy should be at least 8 weeks and continue for at the very least 12 months, but is likely to be much longer. In light of the risks of untreated post-traumatic stress disorder (e.g., suicide and impaired psychosocial functioning), therapy may need to be continued for 2 years or more. Pharmacologic therapy instituted at the time of acute psychologic trauma shows promise for the prevention of post-traumatic stress disorder in the future and warrants further study.
