RESUMO
BACKGROUND: Previous reports have demonstrated a beneficial effect of celecoxib adjunctive therapy for patients with an acute exacerbation of schizophrenia. We investigated the effects of celecoxib augmentation of atypical antipsychotic medications for continuously symptomatic outpatient subjects with schizophrenia to further extend these findings. We hypothesized that celecoxib augmentation therapy would improve psychopathology ratings compared with placebo. METHODS: Thirty-eight symptomatic outpatient subjects meeting DSM-IV criteria for schizophrenia and on a stable dose of an atypical antipsychotic medication for at least three months were randomized to receive 8 weeks of double blind placebo or celecoxib (400 mg/day) augmentation. Measures of psychopathology, functional disability, and extrapyramidal side effects were performed throughout the study. RESULTS: The treatment cohorts did not differ on any of the clinical outcome measures. CONCLUSIONS: Celecoxib augmentation of continuously ill outpatient subjects with schizophrenia did not improve clinical symptoms or measures of disability.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Pirazóis/uso terapêutico , Esquizofrenia/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Antipsicóticos/uso terapêutico , Celecoxib , Método Duplo-Cego , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Placebos , Escalas de Graduação Psiquiátrica , Fatores de TempoRESUMO
BACKGROUND: Studies suggest that schizophrenic patients have an increased prevalence of serum antibodies to neuroblastoma cell proteins migrating at 60 kilodaltons (kDa). We present work identifying and characterizing 60 kDa antigen-antibody interactions. METHODS: Sera from schizophrenic subjects and normal volunteers were screened by Western blotting. Proteins migrating at 60 kDa were characterized by two-dimensional gel electrophoresis and indirect immunofluorescent staining of human epithelial cell (HEp-2) slides. Human brain and bladder cell complementary deoxyribonucleic acid libraries were screened with immunoaffinity-purified antibodies. Complementary deoxyribonucleic acid clones were sequenced and compared with published databases. Proteins were generated by in vitro transcription/translation and expression in an Escherichia coli BL21 system. Immunoprecipitation and immunohistochemistry studies were performed. RESULTS: Fifteen percent (17/117) of schizophrenic subjects and 3% (2/62) of normal volunteers had autoantibodies that reacted with 60 kDa proteins [chi(2)(1) = 4.4, p =.037]. Five percent of subjects had autoantibodies directed against 60 kDa heat shock protein (HSP60) [chi(2)(1) = 3.3, p =.100). Two-dimensional gel electrophoresis identified 13 different proteins migrating at 60 kDa; 5 were splice variants of HSP60, and 2 corresponded with a protein associated with MYC (PAM). CONCLUSIONS: There is an increased prevalence of autoantibodies that bind to proteins migrating at 60 kDa in subjects with schizophrenia. Potential target antigens include HSP60 and PAM.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Autoanticorpos/imunologia , Oxigenases de Função Mista , Esquizofrenia/imunologia , Adulto , Afinidade de Anticorpos , Autoanticorpos/sangue , Autoanticorpos/metabolismo , Western Blotting/métodos , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Chaperonina 60/metabolismo , Clonagem Molecular , Manual Diagnóstico e Estatístico de Transtornos Mentais , Eletroforese em Gel Bidimensional/métodos , Células Epiteliais/metabolismo , Feminino , Imunofluorescência/métodos , Biblioteca Gênica , Células HeLa/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neuroblastoma/metabolismo , Fragmentos de Peptídeos/metabolismo , Testes de Precipitina , Biossíntese de Proteínas , Proteínas Recombinantes/imunologia , Esquizofrenia/sangue , Esquizofrenia/metabolismo , Transcrição Gênica , Ubiquitina-Proteína LigasesRESUMO
This article reviews the impact of depressive and anxiety disorders on quality of life (QOL), disability, and economic burden in the lives of older individuals. Distinctions between the terms QOL, disability, and burden are important in understanding the extent of improvement needed in treatment for elderly patients with depression or anxiety. Treatment efforts should be extended to remediate not only signs and symptoms of psychiatric syndromes but QOL and disability as well; increased understanding toward this end is evolving, yet it is clear that these issues need to be the focus of more investigation.
Assuntos
Transtornos de Ansiedade/psicologia , Transtornos do Humor/psicologia , Qualidade de Vida , Idoso , Humanos , Fatores de RiscoRESUMO
OBJECTIVES: The authors assess the effectiveness of a specialized telepsychiatry training and supervision training model. METHODS: Fifteen residents and eight child fellows rotated through Cedars Sinai Medical Center Telepsychiatry Developmental Disability Clinic and completed questionnaires of knowledge and self-assessed skills at commencement and completion of the rotation. The supervision was on site, side-by-side, and directive. RESULTS: Both the residents and the fellows demonstrated improvement. Increase in knowledge was equal in the study cohorts, while residents' self-assessed skills were significantly greater than the fellows'. CONCLUSION: A telepsychiatry clinic appears to be an appropriate setting in which to provide direct supervision. Exposure to such opportunities early in training may yield a greater impact.
Assuntos
Internato e Residência , Mentores/educação , Psiquiatria/educação , Ensino/métodos , Telemedicina/métodos , Adulto , Criança , Deficiências do Desenvolvimento , Feminino , Humanos , MasculinoRESUMO
Celecoxib augmentation therapy has been reported to enhance the rate of clinical response for patients with schizophrenia. This may be due in part to an effect of celecoxib in the immune dysfunction associated with schizophrenia. Given concerns about the safety of COX-2 inhibitors, studies investigating cytokine levels in medicated patients with schizophrenia are of public health importance. Twenty-eight schizophrenia subjects stabilized on olanzapine or risperidone were randomized to receive 8 wk of celecoxib (400 mg/d) or placebo. Serum soluble IL-2 receptor (sIL-2r) and in-vitro PHA-stimulated whole-blood cytokine production levels were measured at baseline, 1 wk, and 8 wk. Celecoxib augmentation did not alter any of the cytokine parameters measured for the overall study group. However, 1 wk of celecoxib augmentation increased TNF-alpha and IL-2 production levels in olanzapine-treated subjects. These elevations did not persist by week 8. Overall, celecoxib does not significantly modify cytokine levels in medicated schizophrenia subjects.
Assuntos
Citocinas/sangue , Pirazóis/administração & dosagem , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adulto , Benzodiazepinas/administração & dosagem , Celecoxib , Método Duplo-Cego , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Estudos Prospectivos , Risperidona/administração & dosagem , Esquizofrenia/imunologiaRESUMO
Major depressive disorder (MDD) is a common and costly illness. Recent research suggests that MDD is a lifelong condition for many patients. This has stimulated researchers to identify risk factors associated with an increased frequency of relapse and recurrence of major depression. One of the most important of these risk factors is an incomplete response to acute treatment. These data have led investigators to pursue techniques that enhance the acute response of patients to therapy, and study whether long-term treatment with antidepressants may prevent relapse and recurrence of MDD. Data from these trials suggest that continuation and maintenance treatment of MDD confers some protection against deteriorating back into an episode after acute treatment and against developing another episode of MDD.