RESUMO
BACKGROUND: Better treatments for schizophrenia are urgently needed. The therapeutic use of the nitric oxide (NO)-donor sodium nitroprusside (SNP) in patients with schizophrenia has shown promising results. The role of NO in schizophrenia is still unclear, and NO modulation is unexplored in ketamine (KET) animal models to date. In the present study, we compared the behavioral effects of pre- and post-treatment with SNP, glyceryl trinitrate (GTN), and methylene blue (MB) in the acute KET animal model of schizophrenia. The present study was designed to test whether acute SNP, GTN, and MB treatment taken after (therapeutic effect) or before (preventive effect) a single KET injection would influence the behavior of rats in the sucrose preference test, object recognition task and open field. RESULTS: The results showed that KET induced cognitive deficits and hyperlocomotion. Long- term memory improvement was seen with the therapeutic GTN and SNP treatment, but not with the preventive one. MB pretreatment resulted in long-term memory recovery. GTN pre-, but not post-treatment, tended to increase vertical and horizontal activity in the KET model. Therapeutic and preventive SNP treatment consistently decreased KET-induced hyperlocomotion. CONCLUSION: NO donors - especially SNP - are promising new pharmacological candidates in the treatment of schizophrenia. In addition, we showed that the potential impact of NO-related compounds on KET-induced behavioral changes may depend on the temporal window of drug administration.
Assuntos
Antipsicóticos/farmacologia , Azul de Metileno/farmacologia , Nitroglicerina/farmacologia , Nitroprussiato/farmacologia , Esquizofrenia/tratamento farmacológico , Doença Aguda , Animais , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Sacarose Alimentar/administração & dosagem , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Masculino , Atividade Motora , Doadores de Óxido Nítrico/farmacologia , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Percepção Gustatória/efeitos dos fármacos , Resultado do TratamentoRESUMO
BACKGROUND: Neuropsychiatric sequelae are the predominant long-term disability after traumatic brain injury (TBI). This study reports a case of late-onset social anxiety disorder (SAD) following TBI. CASE REPORT: A patient that was spontaneous and extroverted up to 18-years-old started to exhibit significant social anxiety symptoms. These symptoms became progressively worse and he sought treatment at age 21. He had a previous history of traumatic brain injury (TBI) at age 17. Neuroimaging investigations (CT, SPECT and MRI) showed a bony protuberance on the left frontal bone, with mass effect on the left frontal lobe. He had no neurological signs or symptoms. The patient underwent neurosurgery with gross total resection of the lesion and the pathological examination was compatible with intradiploic haematoma. CONCLUSIONS: Psychiatric symptoms may be the only findings in the initial manifestation of slowly growing extra-axial space-occupying lesions that compress the frontal lobe from the outside. Focal neurological symptoms may occur only when the lesion becomes large. This case report underscores the need for careful exclusion of general medical conditions and TBI history in cases of late-onset SAD and may also contribute to the elucidation of the neurobiology of this disorder.
Assuntos
Transtornos de Ansiedade/etiologia , Lesões Encefálicas/psicologia , Lobo Frontal/fisiopatologia , Hemorragia Intracraniana Traumática/diagnóstico , Hemorragia Intracraniana Traumática/psicologia , Transtornos de Ansiedade/diagnóstico , Lobo Frontal/cirurgia , Humanos , Hemorragia Intracraniana Traumática/cirurgia , Masculino , Neuroimagem , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. METHOD: The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300 mg or cannabidiol 600 mg or placebo. RESULTS: The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300 mg performing better than those who received cannabidiol 600 mg. CONCLUSION: The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.
Assuntos
Antipsicóticos/administração & dosagem , Canabidiol/administração & dosagem , Resposta Galvânica da Pele , Transtornos Psicóticos/tratamento farmacológico , Psicologia do Esquizofrênico , Teste de Stroop , Adulto , Análise de Variância , Cognição/efeitos dos fármacos , Cognição/fisiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Esquizofrenia/fisiopatologiaRESUMO
UNLABELLED: Schizophrenia is a severe psychiatric disorder with a complex presentation comprising positive symptoms (e.g.: hallucinations and delusions), negative symptoms (e.g.: social withdrawal, blunted affect) and pervasive cognitive deficits that have been associated with functional decline. The pathophysiology of the disorder is equally complex, with abnormalities known to occur in the molecular, cellular, neurophysiological, and neuroanatomical domains. Despite significant progress in the comprehension of the various manifestations of schizophrenia, the full picture of its etiology remains unknown. As a result, currently available pharmacological treatments have limited efficacy and little has improved since the discovery of the first antipsychotics back in the 1950s. In addition, these medications have significant adverse effects. Differently from other medical areas, the diagnosis of schizophrenia is essentially clinical and dependent on subjective elements. In an attempt to change this, efforts have been directed to find biomarkers of the disorder that could improve diagnostic accuracy and validity, predict treatment response, enable the early identification of individuals at risk of developing schizophrenia and indicate new targets for the development of drugs with better selective, safety, and efficacy profiles. In this article we describe the main potential schizophrenia markers currently under study and suggest avenues for future research in the field. KEY POINTS: - No reliable markers exist for schizophrenia to date. - The identification of schizophrenia markers could increase diagnostic accuracy and treatment efficacy. - The main research lines in the current search for biomarkers are described.
Assuntos
Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Biomarcadores/metabolismo , Encéfalo/fisiopatologia , Humanos , Esquizofrenia/tratamento farmacológicoRESUMO
Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [(99m)Tc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period.
Assuntos
Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Minociclina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Circulação Cerebrovascular/efeitos dos fármacos , Cisteína/análogos & derivados , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Compostos de Organotecnécio , Escalas de Graduação Psiquiátrica , Compostos Radiofarmacêuticos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Processamento de Sinais Assistido por Computador , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Olanzapine is an atypical antipsychotic drug used to treat schizophrenia. Some of the adverse effects related to its use are obesity, hyperlipidemia, type 2 diabetes and hypertension, which may result in development of metabolic syndrome. This study aimed to investigate a possible increase in some anthropometric and biochemical parameters, and the existence of any correlation between them in Brazilian patients with schizophrenia treated with olanzapine in the mid term. METHODS: Thirty subjects with schizophrenia were evaluated, 16 women and 14 men, aged between 18 and 47 years. All patients underwent blood collection and anthropometric measurements at four different times during 12 months of follow up; thus each patient was his or her own control. RESULTS: Evaluation of some anthropometric measurements showed significant differences when comparing the mean values obtained in each of the different data collection times (p < 0.05). However, the biochemical indicators of development of metabolic syndrome measured in our study did not show the same rate of increment, with only the total cholesterol and glucose levels presenting statistically significant changes (p < 0.05), but without the same magnitude of weight change. CONCLUSION: We conclude that medium-term treatment with olanzapine promoted a substantial weight gain and increased visceral fat, while the metabolic profile did not show the same magnitude of change, suggesting a dissociation between weight gain and blood parameters, despite the severe weight gain observed among subjects evaluated.
RESUMO
On August 5-7, 2011, São Paulo was home to the first regional meeting of the Schizophrenia International Research Society (SIRS). Over 400 people from many countries attended the activities and contributed with around 200 submissions for oral and poster presentations. This article summarizes the data presented during the meeting, with an emphasis on the plenary talks and sessions for short oral presentations. For information on the poster presentations, readers are referred to the special issue of Revista de Psiquiatria Clínica (Brazil) dedicated to the conference (available at: http://www.hcnet.usp.br/ipq/revista/vol38/s1/).
Assuntos
Esquizofrenia , Humanos , Neuroimagem , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Esquizofrenia/terapia , Sociedades Médicas , América do SulAssuntos
Antipsicóticos/farmacologia , Encéfalo/diagnóstico por imagem , Minociclina/farmacologia , Esquizofrenia/diagnóstico por imagem , Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Humanos , Masculino , Minociclina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto JovemRESUMO
OBJECTIVE: The last decade has seen increasing evidence of dysfunctions in the endogenous cannabinoid system in schizophrenia and of its relationship with the typical cognitive impairment of the disorder. Studies in animal models, healthy volunteers, and psychotic patients clearly suggest an antipsychotic-like effect of cannabidiol. This study investigated the effects of cannabidiol on selective attention in 28 schizophrenic patients using the Stroop Color Word Test and on these patients' electrodermal responsiveness to auditive stimuli. METHOD: The subjects attended two experimental sessions, the first one without the administration of drugs. In the second session the subjects were divided into three groups that received either a single dose of cannabidiol 300mg or cannabidiol 600mg or placebo. RESULTS: The three groups did not differ significantly with respect to electrodermal measures in the two experimental sessions. When the first and second sessions were compared improved performance was found in all three groups, with patients who received placebo and cannabidiol 300mg performing better than those who received cannabidiol 600mg. CONCLUSION: The single, acute administration of cannabidiol seems to have no beneficial effects on the performance of schizophrenic patients in the Stroop Color Word Test, although the hypothesis that chronic administration may lead to improvement cannot be disregarded.
OBJETIVO: Descobertas relativas a possíveis disfunções do sistema canabinóide endógeno na esquizofrenia e sua relação com o prejuízo cognitivo característico da doença têm aumentado durante a última década. Estudos com modelos animais, voluntários saudáveis e pacientes psicóticos sugerem claramente que o canabidiol possui efeitos antipsicóticos. Este estudo investigou os efeitos do canabidiol sobre a atenção seletiva por meio do Stroop Color Word Test e a responsividade eletrodérmica a estímulos auditivos em 28 pacientes com esquizofrenia. MÉTODO: Duas sessões experimentais foram realizadas, a primeira sem a administração de drogas. Na segunda sessão, os sujeitos foram divididos em três grupos que receberam dose única de canabidiol 300mg, canabidiol 600mg ou placebo. RESULTADOS: Os três grupos não diferiram significativamente no que se refere às medidas eletrodérmicas nas duas sessões experimentais. Os três grupos apresentaram melhora da primeira para a segunda avaliação, com os grupos placebo e canabidiol 300mg superiores ao grupo canabidiol 600mg. CONCLUSÃO: A administração aguda de canabidiol em dose única parece não ter efeitos benéficos sobre o desempenho de pacientes com esquizofrenia no Stroop Color Word Test, embora estes dados não sejam suficientes para refutar a hipótese de que a administração continuada de canabidiol possa resultar em melhora no funcionamento cognitivo em esquizofrenia.