Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

We measured CSF levels of beta-endorphin, an opioid hormone, in 19 patients with infantile autism and in 3 patients with Rett syndrome, and compared them with control values. In infantile autism, CSF levels of beta-endorphin did not differ significantly from those of age-matched controls. There was no significant correlation between CSF levels and clinical symptoms, including self-injurious behavior, pain insensitivity, and stereotyped movement. However, CSF levels of beta-endorphin were significantly higher in the patients with Rett syndrome than in the control (p < .05). Data suggest that neurons containing beta-endorphin may not be involved in patients with infantile autism. Thus, there is no relationship between dysfunction of brain opioid and autism.
J Autism Dev Disord 1997 Apr
PMID:CSF beta-endorphin levels in patients with infantile autism. 910 66

Six children, between 3 and 5 years of age, having infantile autism according to DSM-III-R, were treated for 3 months with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-BH4), a cofactor for tyrosine hydroxylases in the biosynthetic pathway of catecholamines and serotonin. A criterion for inclusion in the study was a relatively low level of R-BH4 in the cerebrospinal fluid. For clinical evaluation, the Parental Satisfaction Survey (PASS) was used every fourth week and the Griffiths Developmental Scales were used before starting and 3 months after completing the treatment. During the treatment period, all parents reported improvements in the child's social functioning-mainly eye contact and desire to interact-and in the number of words or sounds which the child used. Small positive changes were noted on the Griffiths Developmental Scales between the two testing occasions. R-BH4 levels in CSF increased significantly after treatment. The positron emission tomography (PET) study showed that the high value of dopamine D2 receptor binding in the caudate and putamen decreased by about 10% towards the normal level after treatment with R-BH4. The observations in this open study indicate that the drug might be useful for a subgroup of children with autism, but there is a need for a larger double-blind study with a longer treatment period.
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PMID:Possible effects of tetrahydrobiopterin treatment in six children with autism--clinical and positron emission tomography data: a pilot study. 923 97

Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.
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PMID:Gangliosides in cerebrospinal fluid in children with autism spectrum disorders. 976 35

Autism and Rett syndrome (RS) are both developmental disorders of unknown origin. Autism is a behaviourally defined syndrome. RS, which affects girls only, is characterized by a profound learning disability following early normal development, with a consistent cluster of clinical features. Differentiation of RS from infantile autism in the very early stages of the disorders is not always easy. Both syndromes still lack discriminative laboratory markers for accurate diagnosis and differentiation. We decided to compare the CSF nerve-growth factor (NGF) levels of children with infantile autism and children with RS using enzyme-linked immunosorbent assay (ELISA). Our findings of mainly normal CSF NGF in autism and low to negligible values in RS are in agreement with the different morphological and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. CSF NGF could be used as a biochemical marker for differentiation of patients with autism from those with RS.
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PMID:Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism and Rett syndrome. 1021 Feb 46

Autism is a behaviourally defined syndrome characterized by disturbances of social interaction and communication and restrictions of behaviour patterns and imagination. The pathogenesis of autism is unknown but it is suspected that a number of genetic factors may be involved. Neurotrophic factors such as insulin-like growth factor-I (IGF-I) play a role in early brain development. The aim of this study was to determine whether IGF-I levels might be associated with the development of autism. IGF-I levels were measured in the CSF of 11 children with autism (4 females, 7 males; mean age 3.8 years, SD 1.1) using a sensitive radioimmunoassay method and compared with levels in 11 control participants (6 females, 5 males; mean age 3.8 years). Levels of IGF-I in the CSF were statistically significantly lower in the children with autism than in the control children (p=0.03). IGF-I may play a role in pathogenetic mechanisms of autism and the role of neurotrophic factors in autism and other neurodevelopmental diseases should be studied further.
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PMID:Low levels of insulin-like growth factor-I in cerebrospinal fluid in children with autism. 1157 Jun 30

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.
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PMID:Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism. 1554 57

There is a persuasive evidence that autism is highly heritable and likely to be substantially determined by polygenic mechanisms. Nevertheless, some intriguing findings in children raised in conditions of extreme social deprivation suggest that an autistic-like syndrome may occur as a consequence of environmental conditions. A particularly close model of this human syndrome has been studied in rhesus monkeys for almost half a century. Monkeys reared in pathogenic rearing conditions manifest considerable deficits in social interaction and increased self-directed behaviors. We have been interested in the possibility that disruptions in normal social development in non-human primates might be expressed in neuropeptide systems which have emerged in rodent studies as important candidates for a unique social biology. In recent studies, we have described persistently reduced CSF OT levels in male rhesus monkeys with significant social deficits. We also found that OT levels were positively related to the expression of affiliative social behaviors. Alterations were also detected in both CRH and AVP receptor binding patterns in limbic structures likely to influence social and emotional development. Taken together, these data suggest that abnormal rearing influences the development of brain systems critical to normal social and emotional competence in rhesus monkeys and may contribute to the development of autistic-like symptomatology associated with pathogenic rearing histories.
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PMID:Neuropeptides and non-human primate social deficits associated with pathogenic rearing experience. 1574 49

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that manifest in childhood. Immune dysregulation and autoimmune reactivity may contribute to the etiology of ASD and are likely the result of both genetic and environmental susceptibilities. A common environmental contaminant, 2,2',4,4'-tetrabrominated biphenyl (BDE-47), was tested for differential effects on the immune response of peripheral blood mononuclear cells (PBMC) isolated from children with ASD (n=19) and age-matched typically developing controls (TD, n=18). PBMC were exposed in vitro to either 100 nM or 500 nM BDE-47, before challenge with bacterial lipopolysaccharide (LPS), an innate immune activator, with resultant cytokine production measured using the Luminex multiplex platform. The cytokine responses of LPS stimulated PBMC from ASD and TD subjects diverged in the presence of 100 nM BDE. For example, cells cultured from the TD group demonstrated significantly decreased levels of the cytokines IL-12p40, GM-CSF, IL-6, TNFalpha, and the chemokines MIP-1alpha and MIP-1beta following LPS stimulation of PBMC pretreated with 100 nM BDE-47 compared with samples treated with vehicle control (p<0.05). In contrast, cells cultured from subjects with ASD demonstrated an increased IL-1beta response to LPS (p=0.033) when pretreated with 100 nM BDE-47 compared with vehicle control. Preincubation with 500 nM BDE-47 significantly increased the stimulated release of the inflammatory chemokine IL-8 (p<0.04) in cells cultured from subjects with ASD but not in cells from TD controls. These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects were differentially affected when compared with the TD controls suggesting a biological basis for altered sensitivity to BDE-47 in the ASD population.
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PMID:Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders. 1921 Nov 57

Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated peripheral blood monocytes from 17 children with ASD and 16 age-matched typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like receptors (TLR) ligands: TLR 2 (lipoteichoic acid; LTA), TLR 3 (poly I:C), TLR 4 (lipopolysaccharide; LPS), TLR 5 (flagellin), and TLR 9 (CpG-B). Supernatants were harvested from the cell cultures and pro-inflammatory cytokine responses for IL-1beta, IL-6, IL-8, TNFalpha, MCP-1, and GM-CSF were determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a marked increase in pro-inflammatory IL-1beta, IL-6, and TNFalpha responses following TLR 2, and IL-1beta response following TLR 4 stimulation in monocyte cultures from children with ASD (p<0.04). Conversely, following TLR 9 stimulation there was a decrease in IL-1beta, IL-6, GM-CSF, and TNFalpha responses in monocyte cell cultures from children with ASD compared with controls (p<0.05). These data indicate that, monocyte cultures from children with ASD are more responsive to signaling via select TLRs. As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD.
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PMID:Differential monocyte responses to TLR ligands in children with autism spectrum disorders. 1966 4

The blood-brain barrier, the blood-cerebrospinal fluid barrier (BCB) and other specialized brain barriers are increasingly recognized as a major obstacle to the treatment of most brain disorders. The impairment of these barriers has been implicated in neuropathology of several diseases, such as autism, ischemia, multiple sclerosis and Alzheimer disease. This dual function of the blood-neural barriers points out the importance and need for the development of techniques that can evaluate the nature and level of their integrity. Here we report the discovery of CSF secretory Ca(2+)-dependent phospholipase A2 (sPLA2) activity as a measure of BCB permeability. Lumbar CSF from BCB impaired (n=26), multiple sclerosis (n=18) and healthy control (n=32) cases was analyzed using both a newly developed continuous fluorescence assay for CSF sPLA2 activity and CSF/Serum albumin ratio (Q(Alb)), the most common and established method to evaluate BCB permeability. While both measurements showed no significant differences between multiple sclerosis and age-matched normal healthy cases, they were highly correlated. Though the CSF sPLA2 activity and Q(Alb) had over 95% agreement, the former was found to be more sensitive than the latter in measuring low levels of BCB impairment.
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PMID:Cerebrospinal fluid secretory Ca2+-dependent phospholipase A2 activity: a biomarker of blood-cerebrospinal fluid barrier permeability. 2047 Aug 66


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