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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autism is a heterogeneous neurodevelopmental disorder with a variety of different etiologies, but with a heritability estimate of more than 90%. Although the strong correlation between autism and genetic factors has been long established, the exact genetic background of autism is still unclear. This review refers to all the genetic syndromes that have been described in children with pervasive developmental disorders (tuberous sclerosis, fragile X, Down, neurofibromatosis, Angelman, Prader-Willi, Gilles de la Tourette, Williams, etc.). Issues covered include prevalence and main characteristics of each syndrome, as well as the possible base of its association with autism in terms of contribution to the current knowledge on the etiology and genetic base of pervasive developmental disorders.
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PMID:Childhood autism and associated comorbidities. 1708 99

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.
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PMID:Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy. 1710 69

Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder associated with a wide range of physical features and very high rates of numerous neurocognitive manifestations. However, there is great variability of expression of these features and understanding of the mechanisms underlying this variability is still limited. Mental retardation (MR) and male gender are known to be associated with increased risks of psychopathologies in the general population, but no study has examined these subgroups in TSC as possible contributors to the variable expression observed. It has also remained unclear whether familial-sporadic differences may contribute to variable expression. In this postal survey, UK families reported the frequency and range of physical and behavioural abnormalities in 265 children and adolescents with TSC. Analysis revealed no gender or familial-sporadic differences. Children with MR were significantly more likely to have an autism spectrum disorder, attention deficit-related symptoms and speech and language difficulties. They were more likely to have a history of epilepsy, facial angiofibromata and shagreen patches and tended to have a greater number of physical features of the disorder. However, about one third of the children without MR had features suggestive of a developmental disorder. Anxiety symptoms, depressed mood and aggressive outbursts occurred at equally high rates in those with and without MR. These findings show that TSC can place any child or adolescent at significantly increased risk of a range of neurodevelopmental disabilities. These difficulties, often not recognised, require significant clinical and research attention.
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PMID:The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC): a postal survey of UK families. 1726 83

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disorder characterized by benign tumors (hamartomas) in various organs. The brain is one of the most severely affected organs with neuropsychiatric disorders including epilepsy, mental retardation and autism. The identification of TSC genes (TSC1 and TSC2) and their gene products (hamartin and tuberin, respectively), revealed that they function together as a complex. However, mutations in TSC2 are often accompanied by more severe neurologic deficits. Here, we show that hamartin and tuberin play different roles in NGF-treated cultured neuronal cells PC12h. The level of hamartin in PC12h cells was slightly and gradually increased, while those of tuberin rapidly increased upon NGF-induced neuronal differentiation in PC12h cells. Antisense for TSC1 (TSC1-AS) or TSC2-AS reduced expression of hamartin or tuberin, respectively, and enhanced S-phase of cell cycle in PC12h cells. Suppression of hamartin significantly enhanced neurite outgrowth after NGF-treatment in PC12h cells, while suppression of tuberin inhibited neurite outgrowth. Expression of activated V14RhoA reverted TSC1-AS induced abnormal neurite development. These results suggest that loss of hamartin results in abnormal neurite elongation through Rho inactivation in NGF-treated PC12h cells, which may be associated with the neurological manifestations of TSC.
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PMID:Antisense suppression of TSC1 gene product, hamartin, enhances neurite outgrowth in NGF-treated PC12h cells. 1737 23

Because there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that these animals would have an altered regional cerebral O2 consumption that might be associated with autism. We also examined whether the altered cerebral O2 consumption was related to changes in the importance of N-methyl-D-aspartate (NMDA) receptors. Young (4 weeks) male control Long Evans (N = 14) and Eker (N = 14) rats (70-100 g) were divided into control and CGS-19755 (10 mg/kg, competitive NMDA antagonist)-treated animals. Cerebral regional blood flow (14C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. NMDA receptor protein levels were determined by Western immunoblotting. We found significantly increased basal O2 consumption in the cortex (6.2 +/- 0.6 ml O2/min/100 g Eker vs. 4.7 +/- 0.4 Long Evans), hippocampus, cerebellum, and pons. Regional cerebral blood flow was also elevated in Eker rats at baseline, but cerebral O2 extraction was similar. CGS-19755 significantly lowered O2 consumption in the cortex (2.8 +/- 0.3), hippocampus, and pons of the Long Evans rats but had no effect on cortex (5.8 +/- 0.8) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. NMDA receptor protein levels (NR1 subunit) were similar between groups. In conclusion, Eker rats had significantly elevated cerebral O2 consumption and blood flow, but this was not related to NMDA receptor activation. In fact, the importance of NMDA receptors in the control of basal cerebral O2 consumption was reduced. This might have important implications in the treatment of autism.
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PMID:Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D-aspartate blockade: Implications for autism. 1754 50

Psychiatric symptoms were retrospectively assessed in a clinic population of 241 children and adults with tuberous sclerosis complex (TSC). Sixty-six (27%) patients had a history of mood disorder symptoms, 66 (27%) had a history of anxiety disorder symptoms, 73 (30%) had a history of attention-deficit hyperactivity disorder (ADHD) symptoms, and 68 (28%) had a history of aggressive/disruptive behavior disorder symptoms. Significant relationships were found between these symptoms and patient age, gender, genetic mutation, seizure history, surgical history, cognitive impairment, features of autism or pervasive developmental disorder, and neurological manifestations of TSC. In 43 patients seen by at least one of two affiliated psychiatrists, the most common formal diagnoses were anxiety disorders (28%), mood disorders (26%), adjustment disorders (21%), ADHD (21%), and mental disorders not otherwise specified due to general medical condition (42%). Citalopram demonstrated efficacy in treating anxiety and depression, and risperidone, in treating problematic behaviors.
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PMID:Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex. 1793 87

Both cognitive impairment and autism are common in the tuberous sclerosis complex, but the relationship between the 2 diagnoses has not been formally explored. The authors evaluated 20 clinic-referred children with tuberous sclerosis complex at ages 18, 24, 36, and 60 months and classified them as autism, autism spectrum disorder, or normal on the basis of the Autism Diagnostic Observation Schedule. Using the Mullen Scale of Early Learning, cognitive function in each subgroup was assessed. The authors then analyzed the subscores of the Autism Diagnostic Observation Schedule in children with autism. Children with autism showed significantly more global cognitive impairment than those without autism. In addition, all children had some baseline cognitive impairment and the majority had deficits in play scores. The authors conclude that clinic-referred children with tuberous sclerosis complex and autism are at considerable risk for cognitive impairment. These characteristics may help to guide more tailored services for these high-risk children.
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PMID:Characterization of autism in young children with tuberous sclerosis complex. 1816 May 49

Autism is a behavioural syndrome, present from early life and defined by deficient social interaction, language and communication, and play. Variations in symptomatology and in prognosis among characteristic persons display a variety of other signs such as attention deficits, mental retardation and seizures that are not specific to autism and that denote dysfunction in other brain systems. Its aetiology is unknown in the vast majority of cases. There is a small minority of persons in whom autism has a known aetiology, such as fragile X chromosome abnormality, congenital rubella, tuberous sclerosis and a variety of structural abnormalities and metabolic diseases of the brain. A causal treatment is so far not possible, and there remains a regrettable lack of evaluated treatment standards. Prognosis depends on many factors, most notably the limiting factor provided by the severity of the underlying brain dysfunction and its consequences for communication, cognition and other behaviour. ENT specialists are confronted with children, adolescents and even adults in whom autistic disease has already been diagnosed in the course of investigations/treatment. If the suspicion of hearing impairment as the cause of problems in daily life is not confirmed in a patient not hitherto known to have autism ENT specialists should also consider autism in the differential diagnosis. In this report the diagnostic and therapeutic strategies currently applied for autism and its importance for ENT specialists are presented.
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PMID:[Autism spectrum disorders. Current knowledge and importance for ENT specialists]. 1821 5

Since there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that the increased regional cerebral O(2) consumption in the Eker rat might be associated with autism. We also examined whether this increased cerebral O(2) consumption was related to changes in the activity of the gamma-aminobutyric acid (GABA) inhibitory system. Young (4 weeks) male control Long Evans (n=14) and Eker (n=14) rats (70-100g) were divided into control and bicuculline (1mg/kg/min for 2 min then 0.1mg/kg/min for 13 min, GABA(A) receptor antagonist) treated animals. Cerebral regional blood flow ((14)C-iodoantipyrine) and O(2) consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O(2) consumption in the cortex (6.3+/-0.7 ml O(2)/min/100g Eker vs. 5.1+/-0.2 ml O(2)/min/100g control), hippocampus and cerebellum, but not the pons. Regional cerebral blood flow was also elevated in the cortex and hippocampus in Eker rats at baseline, but cerebral O(2) extractions were similar. Bicuculline significantly increased O(2) consumption in the cortex (6.5+/-0.3) and all other regions of the control rats, but had no effect on cortex (5.9+/-1.5) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. In conclusion, Eker rats had significantly elevated cerebral O(2) consumption and blood flow, but this was not affected by GABA receptor blockade. This suggested a reduced activity of the GABA(A) receptor in the brains of Eker rats. This may have important implications in the treatment of autism.
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PMID:Cerebral O(2) consumption in young Eker rats, effects of GABA blockade: implications for autism. 1828 78

Tuberous sclerosis complex (TSC) is an inherited genetic disorder commonly associated with neuropsychiatric complications like epilepsy, mental retardation, autism and other behavioral problems and constitutes about 1-4% of the autistic population. Mental retardation and seizures, particularly infantile spasms are significant risk factors for the development of autism. Patients of TSC with autism are more likely to have temporal tubers than those cases without autism. We describe clinical and neuroimaging features of two such cases of tuberous sclerosis with autism.
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PMID:Correlation of autism with temporal tubers in tuberous sclerosis complex. 1831 Aug 44


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