ABSTRACT
Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, and stereotyped behavior. Environmental factors, such as prenatal exposure to valproic acid (VPA), may contribute to the increased risk of ASD. Since disturbed functioning of the purinergic signaling system has been associated with the onset of ASD and used as a potential therapeutic target for ASD in both clinical and preclinical studies, we analyzed the effects of suramin, a non-selective purinergic antagonist, on behavioral, molecular and immunological in an animal model of autism induced by prenatal exposure to VPA. Treatment with suramin (20 mg/kg, intraperitoneal) restored sociability in the three-chamber apparatus and decreased anxiety measured by elevated plus maze apparatus, but had no impact on decreased reciprocal social interactions or higher nociceptive threshold in VPA rats. Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6). Our results suggest an important role of purinergic signaling modulation in behavioral, molecular, and immunological aberrations described in VPA model, and indicate that the purinergic signaling system might be a potential target for pharmacotherapy in preclinical studies of ASD.
Subject(s)
Autistic Disorder/drug therapy , Disease Models, Animal , Prenatal Exposure Delayed Effects/drug therapy , Purinergic Antagonists/administration & dosage , Receptors, Purinergic , Valproic Acid/toxicity , Animals , Anticonvulsants/toxicity , Autistic Disorder/chemically induced , Autistic Disorder/metabolism , Brain/drug effects , Brain/metabolism , Female , Locomotion/drug effects , Locomotion/physiology , Male , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Rats , Receptors, Purinergic/metabolism , Suramin/administration & dosageABSTRACT
The central and peripheral nervous system is built by a network of many different neuronal phenotypes together with glial and other supporting cells. The repertoire of expressed receptors and secreted neurotransmitters and neuromodulators are unique for each single neuron leading to intracellular signaling cascades, many of them involving intracellular calcium signaling. Here we suggest the use of calcium signaling analysis upon specific agonist application to reliably identify neuronal phenotypes, being important not only for basic science, but also providing a reliable tool for functional characterization of cells prior to transplantation. Calcium imaging provides various cellular information including signaling amplitudes, cell localization, duration, and frequency. Microfluorimetry reveals a signal summarizing the entire population, and its use is indicated for high-throughput screening purposes.
Subject(s)
Calcium Signaling , Calcium/analysis , Fluorometry/methods , Neurogenesis , Neurons/cytology , Animals , Calcium/metabolism , Cell Culture Techniques/methods , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Humans , Neurons/metabolismSubject(s)
Child , Humans , Male , Bipolar Disorder/complications , Tourette Syndrome/complications , Antimanic Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Bipolar Disorder/drug therapy , Drug Therapy, Combination , Risperidone/therapeutic use , Tourette Syndrome/drug therapy , Valproic Acid/therapeutic useSubject(s)
Bipolar Disorder/complications , Tourette Syndrome/complications , Antimanic Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Bipolar Disorder/drug therapy , Child , Drug Therapy, Combination , Humans , Male , Risperidone/therapeutic use , Tourette Syndrome/drug therapy , Valproic Acid/therapeutic useABSTRACT
Family, twin and segregation analysis have provided evidences that genetic factors are implicated in the susceptibility for obsessive-compulsive disorder (OCD). Several lines of research suggest that the dopaminergic system may be involved in the pathophysiology of OCD. Thus, the aim of the present study was to investigate a possible association between a polymorphism located in intron 8 of the dopamine transporter gene (SLC6A3) and OCD in a Brazilian sample composed by 208 patients and 865 healthy controls. No statistical differences were observed in allelic and genotype distributions between cases and controls. No association was also observed when the sample was divided according to specific phenotypic features such as gender, presence of tic disorders, co-morbidity, and age at onset of obsessive-compulsive symptoms (OCS). Our results suggest that the intron 8 VNTR of the SLC6A3 investigated in this study is not related to the susceptibility for OCD in our Brazilian sample.
Subject(s)
Dopamine Plasma Membrane Transport Proteins/genetics , Obsessive-Compulsive Disorder/genetics , Polymorphism, Genetic/genetics , Alleles , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Introns/genetics , MaleABSTRACT
Family, twin and segregation analysis have provided evidences that genetic factors are implicated in the susceptibility for obsessive-compulsive disorder (OCD). Several lines of research suggest that the dopaminergic system may be involved in the pathophysiology of OCD. Thus, the aim of the present study was to investigate a possible association between a polymorphism located in intron 8 of the dopamine transporter gene (SLC6A3) and OCD in a Brazilian sample composed by 208 patients and 865 healthy controls. No statistically differences were observed in allelic and genotype distributions between cases and controls. No association was also observed when the sample was divided according to specific phenotypic features such as gender, presence of tic disorders co-morbidity and age at onset of obsessive-compulsive symptoms (OCS). Our results suggest that the intron 8 VNTR of the SLC6A3 investigated in this study is not related to the susceptibility for OCD in our Brazilian sample.
Estudos de família, gêmeos e de segregação têm demonstrado que fatores genéticos estão envolvidos na susceptibilidade para o desenvolvimento do transtorno obsessivo-compulsivo (TOC). Várias linhas de pesquisa sugerem que o sistema dopaminérgico possa estar envolvido na fisiopatologia do TOC. Assim, o objetivo do presente estudo foi investigar uma possível associação entre o polimorfismo localizado no intron 8 do gene do transportador da dopamina (SLC6A3) e o TOC em uma amostra brasileira composta por 208 pacientes e 865 controles sadios. Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos de pacientes e controles. Nenhuma associação também foi observada quando as amostras foram divididas de acordo com características fenotípicas específicas, tais como gênero, presença de co-morbidade com tiques e idade de início dos sintomas obsessivo-compulsivo (SOC). Nossos resultados sugerem que o VNTR do intron 8 investigado neste estudo não está relacionado com o TOC na nossa amostra brasileira.
Subject(s)
Female , Humans , Male , Dopamine Plasma Membrane Transport Proteins/genetics , Obsessive-Compulsive Disorder/genetics , Polymorphism, Genetic/genetics , Alleles , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Introns/geneticsABSTRACT
OBJECTIVE: To compare the effectiveness of group cognitive-behavioral therapy (GCBT) and of sertraline in treatment-naïve children and adolescents with obsessive-compulsive disorder. METHOD: Between 2000 and 2002, 40 subjects between 9 and 17 years old were randomized to receive GCBT (n = 20) or sertraline (n = 20). GCBT consisted of a manual-based 12-week cognitive-behavioral protocol adapted for groups, and treatment with sertraline involved medication intake for 12 weeks. Subjects were assessed before, during, and after treatment (at 1, 3, 6, and 9 months after treatment conclusion). Primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale. Repeated-measures analyses of variance were done. RESULTS: Both GCBT and sertraline conditions had significant improvement in obsessive-compulsive disorder symptoms as measured by the Children's Yale-Brown Obsessive-Compulsive Scale after 12 weeks of treatment. After the 9-month follow-up period, subjects in the GCBT condition had a significantly lower rate of symptom relapse than those in the sertraline group. CONCLUSIONS: The treatment with GCBT may be effective in decreasing obsessive-compulsive symptoms in childhood obsessive-compulsive disorder and should be considered as an alternative to either individual cognitive-behavioral therapy or a medication, such as sertraline. Results support the effectiveness and the maintenance of gains of GCBT in the treatment of youngsters with obsessive-compulsive disorder.
Subject(s)
Cognitive Behavioral Therapy , Obsessive-Compulsive Disorder/therapy , Psychotherapy, Group , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sertraline/therapeutic use , Adolescent , Child , Female , Humans , Male , Obsessive-Compulsive Disorder/diagnosis , Outcome and Process Assessment, Health CareSubject(s)
Humans , Child , Adolescent , Anxiety Disorders/diagnosis , Anxiety Disorders/therapy , Phobic Disorders/therapyABSTRACT
Introdução: Alguns pacientes com transtorno obsessivo-compulsivo (TOC) de início na infância apresentam características clínicas que talvez justifiquem a inclusão destes em subgrupos distintos. Vários autores têm se dedicado a investigar a utilidade e a validade clínica dessa categorização de TOC infantil. Por outro lado, há evidências de que TOC poderia ser um transtorno devido a anormalidades no desenvolvimento de estruturas e circuitos no sistema nervoso central. O presente estudo tem como objetivo fazer uma revisão sobre o estado atual de conhecimento de aspectos neurobiológicos ligados ao TOC de início precoce. Metodologia: Revisão de artigos na literatura por meio de pesquisa em medline sobre características clínicas e estudos de neuroimagem de TOC de início na infância, sobre casos de coréia de Sydenham com manifestações psiquiátricas associadas em crianças e sobre associação de tiques (transtorno de Gilles de la Tourette e outros) e TOC infantil. Resultados: Transtorno do espectrum obsessivo-compulsivo incluindo tiques, sintomas obsessivo-compulsivos e outros distúrbios relacionados, de início pré-peberal, parece constituir um subgrupo clínico distinto, com história familiar positiva para tiques e TOC e resposta favorável, em alguns casos, ao tratamento com associação com neurolépticos. Manifestações de coréia de Sydenham associada a sintomas de TOC, reforçam a idéia de alterações nos gânglios da base envolvidas com fisiopatologia de TOC infantil. Estudos de neuroimagem estrutural em crianças e adolescentes com TOC apontam para alterações no desenvolvimento de estruturas subcorticais e de córtex pré-frontal na etiopatogenia desse transtorno. Conslusões: Esses resultados preliminares chamam a atenção para a importância de estudos nessa população sobre esse tema.
Subject(s)
Humans , Male , Female , Child , Obsessive-Compulsive Disorder/physiopathology , Obsessive-Compulsive Disorder/epidemiology , Age of OnsetABSTRACT
Este trabalho é um estudo retrospectivo, sobre as possíveis causas de retardo mental, realizado através da análise dos prontuários do Instituto de Psiquiatria do HC-FMUSP, com hipótese diagnóstica de oligofrenia, associada ou nao a outras condiçoes. Foram selecionados todos os casos atendidos em primeira consulta, no período de novembro de 1993 a novembro de 1995 (n=27 pacientes). Classificados, primeiramente, de acordo com o grau de retardo mental em déficit leve (Q.I. entre 70 e 50) e moderado ou severo (Q.I. abaixo de 50) e, a seguir, de acordo com fatores etiológicos pré, peri, pós-natais e etiologia desconhecida. Foram encontrados 48,1 por cento de causas pré-natais, 25,9 por cento perinatais, 7,4 por cento pós-natais e 29,6 por cento desconhecidas. Causas específicas foram encontradas ou suspeitadas emm 64,7 por cento dos pacientes com oligofrenia leve e em 80 por cento dos pacientes com oligofrenia maior que leve. Estes últimos dados se aproximam do referido pela literatura. A maior fonte de informaçoes a respeito da etiologia foram dados de anamnese, pouco contribuindo os exames laboratoriais disponíveis, na época da consulta psiquiátrica.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Intellectual Disability/etiology , Retrospective Studies , Intellectual Disability/classificationABSTRACT
O presente trabalho traz uma revisäo sobre neuroimagem em transtorno obsessivo-complusivo, analisando os achados em trabalhos publicados nos últimos cinco anos. Tais técnicas de exame permitiram a ocasiäo de estudar "in vivo" o que pode ocorrer no cérebro de pessoas que apresentam transtornos psiquiátricos. Em pacientes com transtorno obsessivo-compulsivo, exames de neuroimagem estruturais mostraram alteraçöes, como: aumento de volume ventricular em uma parcela destes pacientes e aumento do nucleo caudado unilateral (em geral a esquerda)...
Subject(s)
Humans , Central Nervous System , Obsessive-Compulsive Disorder , Regional Blood Flow , Cerebrum/blood supply , Cerebrum/pathology , Diagnosis, Dual (Psychiatry)ABSTRACT
Caso clinico desde 1989, quando se iniciou com quadro depressivo intenso, com manifestacoes da sindrome de Cotard. Durante as fases depressivas, os sintomas psicoticos eram importantes; seguiam-se fases hipomaniacas. Com boa resposta ao tratamento com carbonato de litio.
