RESUMO
Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder characterized by impairments in social behaviors and communication. Oxytocin and its signaling pathway are related to a range of human behaviors, from facial expression recognition to aggressive behaviors, and have been suggested as involved in the etiology of ASD. Our aim was to evaluate the influence of two polymorphisms (rs1042778, rs53576) at the oxytocin receptor gene (OXTR) on ASD diagnosis and on specific ASD-related clinical symptoms (seizures, panic, and aggressive behaviors). We also assessed if these SNPs could be related to changes in OXTR availability and functionality using a bioinformatic approach. The sample was composed by 209 probands with ASD and their biological parents. Family-based approach and logistic regression models were used to investigated the outcomes. We observed that panic and aggressive behaviors were nominally associated with presence of rs1042778 T allele (P = 0.019/Pcorr = 0.114; P = 0.046/Pcorr = 0.276 respectively). Also, in the family-based analysis, a trend towards association with ASD susceptibility was observed for rs1042778 (G allele) (P = 0.066). In a bioinformatic approach, we demonstrated that rs1042778 G allele is determinant for the binding of the transcription factor MAZ, suggesting that when the T allele is present, the absence of MAZ binding might be associated with lower transcription levels of the OXTR gene. The overall findings suggest that the OXTR gene may play a role in ASD diagnosis and some of its clinical phenotypes, supported by previous animal and clinical studies. Further investigations are necessary to replicate our findings and fully understand the effects of the oxytocin pathway on ASD.
Assuntos
Transtorno do Espectro Autista/genética , Polimorfismo de Nucleotídeo Único , Receptores de Ocitocina/genética , Adolescente , Agressão , Transtorno do Espectro Autista/diagnóstico , Criança , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Masculino , Pânico , Receptores de Ocitocina/metabolismo , Fatores de Transcrição/metabolismoRESUMO
The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80% of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Adulto , Fatores Etários , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , PrognósticoRESUMO
The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80
of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.
Assuntos
Deficiências do Desenvolvimento/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Adulto , Criança , Deficiências do Desenvolvimento/diagnóstico , Fatores Etários , Feminino , Humanos , Masculino , Prognóstico , Progressão da Doença , Seguimentos , Transtornos Globais do Desenvolvimento Infantil/diagnósticoRESUMO
The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80
of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.
Assuntos
Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Adulto , Fatores Etários , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , PrognósticoRESUMO
The 5-HTTLPR polymorphism of serotonin transporter gene is widely investigated in association studies in autism spectrum disorders (ASD). The results of such studies, however, remain controversial possibly due to the great genetic heterogeneity related to ASD and the lack of evaluation of the triallelic functional structure of 5-HTTLPR. This study tested for association between the 5-HTTLPR and ASD in a Brazilian sample by case-control and family-based association test (FBAT) methods, considering the biallelic and triallelic structures of this polymorphism. In addition, we performed an exploratory analysis of associations between specific clinical outcomes of ASD patients and 5-HTTLPR as well as several prenatal environmental factors. Genotyping was achieved in 151 ASD patients, 179 unrelated controls and 105 complete trios. There was no evidence of association between the 5-HTTLPR with ASD in both case-control and FBAT tests, but the LaLa 5-HTTLPR genotype was associated with mood instability in patients (P=0.006). The prenatal exposure to potential neuroteratogenic drugs was associated with epilepsy (P<0.001). Our findings suggest that the 5-HTTLPR is not associated with ASD in the Brazilian population, even considering the triallelic structure. Additionally, this study suggested a role of the 5-HTTLPR and environmental factors in the clinical expression of ASD.
Assuntos
Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Afeto/fisiologia , Análise de Variância , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Meio Ambiente , Epilepsia/induzido quimicamente , Feminino , Frequência do Gene , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Escalas de Graduação Psiquiátrica , Fatores de Risco , Análise de Sequência de DNA , Inquéritos e QuestionáriosRESUMO
With the goal of presenting follow-up data from patients seen at the Refractory Epilepsy out-patient clinic of the Hospital de Clínicas de Porto Alegre (HCPA), Brazil, we reviewed the literature on childhood and adolescent epilepsy and epileptic syndromes with indication for surgical treatment. The International League Against Epilepsy's Subcommission for Pediatric Epilepsy Surgery recommends surgical evaluation for cortical dysplasia, tuberous sclerosis complex, polymicrogyria, hypothalamic hamartoma, hemispheric syndromes, Sturge-Weber, Rasmussen, Landau-Kleffner and other situations such as tumors or cerebrovascular injury. The Subcommission proposes the creation of referral centers with functional methods of evaluation, structural imaging, and a multidisciplinary team that includes neurologists, neurosurgeons, neurophysiologists, neuropediatricians, neuropsychologists, pathologists, neuroradiologists and eletroneurophysiology technicians. Creating these centers in developing countries is possible with the cooperation of other regions. Studies have shown improvement in quality of life with less frequent seizures. At HCPA, we provide evaluations and ongoing clinical management of patients with medically refractory epilepsy. Epilepsy surgery is potentially curative and is particularly useful for the pediatric population.