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

Heparan sulfate regulates diverse cell-surface signaling events, and its roles in the development of the nervous system recently have been increasingly uncovered by studies using genetic models carrying mutations of genes encoding enzymes for its synthesis. On the other hand, the role of heparan sulfate in the physiological function of the adult brain has been poorly characterized, despite several pieces of evidence suggesting its role in the regulation of synaptic function. To address this issue, we eliminated heparan sulfate from postnatal neurons by conditionally inactivating Ext1, the gene encoding an enzyme essential for heparan sulfate synthesis. Resultant conditional mutant mice show no detectable morphological defects in the cytoarchitecture of the brain. Remarkably, these mutant mice recapitulate almost the full range of autistic symptoms, including impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, as well as some associated features. Mapping of neuronal activation by c-Fos immunohistochemistry demonstrates that neuronal activation in response to social stimulation is attenuated in the amygdala in these mice. Electrophysiology in amygdala pyramidal neurons shows an attenuation of excitatory synaptic transmission, presumably because of the reduction in the level of synaptically localized AMPA-type glutamate receptors. Our results demonstrate that heparan sulfate is critical for normal functioning of glutamatergic synapses and that its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism.
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PMID:Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. 2241

We have recently described four principal pathogenetic components in autism: (I) circadian and sensory dysfunction, (II) immune abnormalities, (III) neurodevelopmental delay, and (IV) stereotypic behaviors. Using hierarchical and k-means clustering, the same 245 patients assessed in our principal component analysis can be partitioned into four clusters: (a) 43 (17.6%) have prominent immune abnormalities accompanied by some circadian and sensory issues; (b) 44 (18.0%) display major circadian and sensory dysfunction, with little or no immune symptoms; (c) stereotypies predominate in 75 (31.0%); and (d) 83 (33.9%) show a mixture of all four components, with greater disruptive behaviors and mental retardation. The "immune" component provides the largest contributions to phenotypic variance (P = 2.7 x 10(-45)), followed by "stereotypic behaviors." These patient clusters may likely differ in genetic and immune underpinnings, developmental trajectories, and response to treatment.
Autism Res 2012 Apr
PMID:Cluster analysis of autistic patients based on principal pathogenetic components. 2243 Dec 51

The effects of 14 weeks of Kata techniques training on stereotypic behaviors of children with autism spectrum disorders (ASD) were investigated. The study included 30 eligible (diagnosed ASD, school age) children with ages ranging from 5 to 16 years whom they assigned to an exercise (n=15) or a no-exercise control group (n=15). Participants of the exercise group received Kata techniques instruction four times per week for 14 weeks (56 sessions). Stereotypy was assessed at baseline (pre-intervention), week 14 (post-intervention), and at one month follow up in both groups. Results showed that Kata techniques training significantly reduced stereotypy in the exercise group. Following participation in Kata techniques training, stereotypy decreased from baseline levels by a M of 42.54% across participants. Interestingly, after 30 days of no practice, stereotypy in the exercise group remained significantly decreased compared to pre-intervention time. The participants of the control group did not show significant changes in the stereotypy. Teaching martial arts techniques to children with ASD for a long period of time consistently decreased their stereotypic behaviors.
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PMID:Kata techniques training consistently decreases stereotypy in children with autism spectrum disorder. 2250 44

Mutations in neurexin and neuroligin genes have been associated with neurodevelopmental disabilities including autism. Autism spectrum disorder is diagnosed by aberrant reciprocal social interactions, deficits in social communication, and repetitive, stereotyped patterns of behaviors, along with narrow restricted interests. Mouse models have been successfully used to study physiological and behavioral outcomes of mutations in the trans-synaptic neurexin-neuroligin complex. To further understand the behavioral consequences of Neuroligin2 (NLGN2) mutations, we assessed several behavioral phenotypes relevant to autism in neuroligin2 null (Nlgn2(-/-)), heterozygote (Nlgn2(+/-)), and wildtype (Nlgn2(+/+)) littermate control mice. Reduced breeding efficiency and high reactivity to handling was observed in Nlgn2(-/-) mice, resulting in low numbers of adult mice available for behavioral assessment. Consistent with previous findings, Nlgn2(-/-) mice displayed normal social behaviors, concomitant with reduced exploratory activity, impaired rotarod performance, and delays on several developmental milestones. No spontaneous stereotypies or repetitive behaviors were detected. Acoustic, tactile, and olfactory sensory information processing as well as sensorimotor gating were not affected. Nlgn2(-/-) pups isolated from mother and littermates emitted fewer ultrasonic vocalizations and spent less time calling than Nlgn2(+/+) littermate controls. The present findings add to the growing literature on the role of neurexins and neuroligins in physiology and behavior relevant to neurodevelopmental disorders.
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PMID:Developmental delays and reduced pup ultrasonic vocalizations but normal sociability in mice lacking the postsynaptic cell adhesion protein neuroligin2. 2282 Feb 33

This is an overview of stereotypic behavior in autistic spectrum disorder (ASD). This repetitive, nonfunctional, fixed pattern of behavior is associated with autism severity but it is not specific for ASD. There are a wide range of behaviors mentioned as stereotypies. It usually starts in early childhood and its severity is associated with outcomes and severity of autism in adolescence and adulthood. It is usually co-morbid with other psychiatric problems and its pathophysiology is not exactly known. Management is most likely behavioral. There are some reports regarding efficacy of antipsychotics for its management. Further studies should be conducted to improve our knowledge about it and our ability to differentiate it from tics.
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PMID:Clinical approach to motor stereotypies in autistic children. 2305 97

Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a 'synapse disorder'. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of <0.00001 and a genotype predictability of 100% for male and of >83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity.
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PMID:Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism. 2318 21

Rett syndrome (RTT, MIM#312750) is a neurodevelopmental disorder that is classified as an autism spectrum disorder. Clinically, RTT is characterized by psychomotor regression with loss of volitional hand use and spoken language, the development of repetitive hand stereotypies, and gait impairment. The majority of people with RTT have mutations in Methyl-CpG-binding Protein 2 (MECP2), a transcriptional regulator. Interestingly, alterations in the function of the protein product produced by MECP2, MeCP2, have been identified in a number of other clinical conditions. The many clinical features found in RTT and the various clinical problems that result from alteration in MeCP2 function have led to the belief that understanding RTT will provide insight into a number of other neurological disorders. Excitingly, RTT is reversible in a mouse model, providing inspiration and hope that such a goal may be achieved for RTT and potentially for many neurodevelopmental disorders.
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PMID:The relationship of Rett syndrome and MECP2 disorders to autism. 2322 51

In autism, stereotypies are frequent and disabling, and whether they correspond to a hyperkinetic movement disorder, a homeostatic response aiming at sensory modulation, or a regulator of arousal remains to be established. So far, it has been challenging to distinguish among these different possibilities, not only because of lack of objective and quantitative means to assess stereotypies, but in our opinion also because of the underappreciated diversity of their clinical presentations. Herein, we illustrate the broad spectrum of stereotypies and demonstrate the usefulness of video-assisted clinical observations of children with autism. The clips presented were extracted from play sessions of 129 children with autism disorder. We conclude that compared to widely used questionnaires and interviews, systematic video observations provide a unique means to classify and score precisely the clinical features of stereotypies. We believe this approach will prove useful to both clinicians and researchers as it offers the level of detail from retrievable images necessary to begin to assess effects of age and treatments on stereotypies, and to embark on the type of investigations required to unravel the physiological basis of motor behaviors in autism.
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PMID:Stereotypies in autism: a video demonstration of their clinical variability. 2331 44

Children's symptoms of autism are robustly linked to diminished parent well-being and relationship distress, however they are less clearly linked to other aspects of family development. We focused on child atypical symptoms (i.e., behavioral stereotypies) and investigated relations to parental stress and the parenting alliance. We verified that relations between atypicality and parenting stress were partially mediated by a child-focused aspect of the parenting alliance. These results suggested that parents of highly atypical children reported less stress than parents of children with low levels of these behaviors, an effect that acted through an assessment of the parenting partner as highly involved with the child. However, parents with highly atypical children did not report a similarly better self-focused parenting alliance, indicating that direct emotional support from the partner did not differ between the groups. We discuss the possibility that, among parents who stay together in the face of severe child disability, enhanced perceptions of parenting are not uncommon.
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PMID:Aligning over the child: parenting alliance mediates the association of autism spectrum disorder atypicality with parenting stress. 2347

This study reports on the relationship between motor stereotypies and impairments in executive functions (EF) in children with Autistic Disorder (AD) and in children with Developmental Language Disorders (DLD). We hypothesized that low EF performance would predict higher frequency and longer durations of stereotypies in the AD group only. Twenty-two children (age range = 7-9 years, 6 months, girls = 5) with AD were recruited from a longitudinal multi-site study and compared to twenty-two non-autistic children with DLD (age range = 7-9 years, 6 months, girls = 5). The two groups were matched on non-verbal IQ and demographic characteristics. Frequency and duration of stereotypies were coded from videotaped semi-structured play sessions. EF measures included the Wisconsin Card Sorting Task (WCST) Categories, Wechsler Intelligence Scale for Children-Revised (WISC-R) Mazes, and Stanford-Binet Fourth Edition (SB-IV) Matrices. The scores for frequency and duration of stereotypies were higher in the AD group. Separate linear regressions revealed that group status, EF, and their interactions predict stereotypies. Specifically, lower EF scores predicted higher frequencies and longer durations of stereotypies in the AD group only. Analyses controlled for age, gender, and parent education. Findings suggest that in AD, EF impairments and stereotypies may be linked to shared brain pathways.
Res Autism Spectr Disord 2012 Jul 01
PMID:Relationship between executive functions and motor stereotypies in children with Autistic Disorder. 2363 8


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