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 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
In this randomized, open-label, 8-week comparative study, the efficacy and safety of venlafaxine and fluoxetine were assessed in outpatients with major depression. One hundred forty-five patients were assigned to receive venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily. On day 15, if clinically indicated to improve patient response, the dosage could be increased at the investigator's discretion to venlafaxine 75 mg twice daily or fluoxetine 40 mg once daily. One hundred forty-five patients were evaluated for safety and 110, for efficacy. The mean age was 37 years, and 70% of the patients were female. In both treatment groups, mean scores on the Hamilton Depression Rating Scale decreased significantly between baseline (27.8, venlafaxine; 29.2, fluoxetine) and the end of the study (8.7, venlafaxine; 8.2, fluoxetine). Similarly, mean scores on the Montgomery-Asberg Depression Rating Scale decreased significantly between baseline (31.4, venlafaxine; 31.6, fluoxetine) and the end of the study (8.3, venlafaxine; 7.6, fluoxetine). In venlafaxine patients, the most common adverse events were nausea (44.3%), headache (40.0%), insomnia (31.4%), dizziness (30.0%), and dry mouth (22.9%); in fluoxetine patients, they were headache (32.0%), nausea (28.0%), insomnia (24.0%), anxiety (21.3%), sleepiness (20.0%), and generalized tremor (20.0%). The results of this study indicate that venlafaxine is effective and well tolerated for the treatment of major depression at doses of 37.5 or 75 mg twice daily and not significantly different from fluoxetine 20 or 40 mg once daily.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Cicloexanóis/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Fluoxetina/uso terapêutico , Adolescente , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Cicloexanóis/efeitos adversos , Transtorno Depressivo/psicologia , Feminino , Fluoxetina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Cloridrato de VenlafaxinaRESUMO
Sodium valproate (VA) and clonazepam (CLZ) were combined in the treatment of 4 patients with panic disorders (PD) who were resistant to several antipanic drug treatments. A significant improvement was found in the symptomatology of these patients, but relapses occurred when CLZ dosage was reduced. A potentiation of the GABAergic properties of VA and clonazepam is postulated. This combined treatment could be advantageous for some treatment-resistant PD patients but needs to be studied further.