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

The purpose of this article is to provide an overview of the behavioral phenotype of FMR1 mutations, including fragile X syndrome (FXS) in order to better understand the clinical involvement of individuals affected by mutations in this gene. FXS is associated with a wide range of intellectual and behavioral problems, some relatively mild and others quite severe. FXS is the most common cause of inherited intellectual disability and one of the most prevalent genetic causes of autism spectrum disorder. Learning difficulties, attentional problems, anxiety, aggressive behavior, stereotypies, and mood disorders are also frequent in FXS. Recent studies of children and adults have identified associations between FMR1 premutation and many of the same disorders. We examine the neurobehavioral phenotypes of FXS and FMR1 premutation as they manifest across the lifespan of the individual.
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PMID:The behavioral phenotype of FMR1 mutations. 2098 77

Tourette syndrome (TS) and stereotypy in autism spectrum disorders (ASDs) are 2 common movement disorders in childhood. The objective of this review was to summarize randomized controlled trials published over the past 5 years as an update of the current pharmacotherapeutic options for the treatment of tics, TS, and motor stereotypies in children with ASD. We searched MEDLINE (2005-May 2010) for randomized controlled trials of medications used for the treatment of these disorders. For the treatment of tics in TS, 2 trials suggest that levetiracetam is not effective, whereas 1 trial found that topiramate was effective. Single clinical trials of metoclopramide, atomoxetine, and ondansetron were of limited quality, preventing conclusions to be made regarding the usefulness of these treatments for tic disorders. For the treatment of stereotypy in children with ASD, risperidone has been shown in both a Cochrane review in 2006 and 2 subsequent randomized control trials to be effective. The addition of pentoxifylline to risperidone may have added benefit. Haloperidol did not improve stereotypy and was poorly tolerated. There is good evidence that aripiprazole is effective in the treatment of sterotypies in children with ASD. A large randomized trial of citalopram did not show any improvement in stereotypy. Single trials of levetiracetam, guanfacine, and atomoxetine suggest they are not useful in the reduction of stereotypy in children with ASD.
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PMID:Pharmacotherapeutics of Tourette syndrome and stereotypies in autism. 2118 32

Autism is a neurodevelopmental disorder that is currently diagnosed by the presence of three behavioral criteria (1) qualitative impairments in reciprocal social interactions, (2) deficits in communication, including delayed language and noninteractive conversation, and (3) motor stereotypies, repetitive behaviors, insistence on sameness, and restricted interests. This chapter describes analogous behavioral assays that have been developed for mice, including tests for social approach, reciprocal social interactions, olfactory communication, ultrasonic vocalizations, repetitive and perseverative behaviors, and motor stereotypies. Examples of assay applications to genetic mouse models of autism are provided. Robust endophenotypes that are highly relevant to the core symptoms of autism are enabling the search for the genetic and environmental causes of autism, and the discovery of effective treatments.
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PMID:Mouse models of autism: testing hypotheses about molecular mechanisms. 2122 9

Restricted and repetitive behaviors (RRBs) are a core symptom of autism spectrum disorders (ASD). There has been an increased research emphasis on repetitive behaviors; however, this research primarily has focused on phenomenology and mechanisms. Thus, the knowledge base on interventions is lagging behind other areas of research. The literature suggests there are evidence-based practices to treat "lower order" RRBs in ASD (e.g., stereotypies); yet, there is a lack of a focused program of intervention research for "higher order" behaviors (e.g., insistence on sameness). This paper will (a) discuss barriers to intervention development for RRBs; (b) review evidence-based interventions to treat RRBs in ASD, with a focus on higher order behaviors; and (c) conclude with recommendations for practice and research.
J Autism Dev Disord 2012 Jun
PMID:Evidence-based behavioral interventions for repetitive behaviors in autism. 2158 49

Communication skills deficits and stereotyped behaviors are frequently found among people with pervasive developmental disabilities like autism. These communication and behavioral oddities of autism are often considered to be difficult to treat and are challenging. Picture exchange communication system (PECS) is a six-phase picture system based on applied behavior analysis and is specially designed to overcome these communication difficulties in children with autism by encouraging the child to be the communication initiator. The present paper throws light on the process of using PECS along with other traditional behavioral approaches in managing communication deficits and behavioral stereotypies in a seven-year-old male child diagnosed as having childhood autism. The identified target behaviors of repeated head turning, flapping his hands, poor communication skills were assessed using various rating scales including visual analogue scale as per clinician observation and parental reports and managed using PECS as an adjunct to traditional behavioral techniques of contingency management, differential reinforcement, task direction and reprimand. Outcome was assessed using same tools after thirty-two sessions of interventions spread over three months. Significant improvements of around 60% were observed in the target behaviors.
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PMID:Effects of picture exchange communication system on communication and behavioral anomalies in autism. 2171 76

BTBR T+tf/J (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors, showing deficiencies in social behaviors; reduced or unusual ultrasonic vocalizations in conspecific situations; and enhanced, repetitive self-grooming. Recent studies have described their behaviors in a seminatural visible burrow system (VBS); a Social Proximity Test in which avoidance of a conspecific is impossible; and in an object approach and investigation test evaluating attention to specific objects and potential stereotypies in the order of approaching/investigating objects. VBS results confirmed strong BTBR avoidance of conspecifics and in the Social Proximity Test, BTBR showed dramatic differences in several close-in behaviors, including specific avoidance of a nose-to-nose contact that may potentially be related to gaze-avoidance. Diazepam normalized social avoidance by BTBRs in a Three-Chamber Test, and some additional behaviors - but not nose to nose avoidance - in the Social Proximity Test. BTBR also showed higher levels of preference for particular objects, and higher levels of sequences investigating 3- or 4-objects in the same order. Heparan sulfate (HS) associated with fractal structures in the subventricular zone of the lateral ventricles was severely reduced in BTBR. HS may modulate the functions of a range of growth and guidance factors during development, and HS abnormalities are associated with relevant brain (callosal agenesis) and behavioral (reductions in sociality) changes; suggesting the value of examination of the dynamics of the HS system in the context of autism.
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PMID:BTBR T+tf/J mice: autism-relevant behaviors and reduced fractone-associated heparan sulfate. 2174 2

Balb/c mice display deficits of sociability; for example, they show reduced locomotor activity in the presence of an enclosed or freely-moving social stimulus mouse. Transgenic mice with defective or diminished expression of NMDA receptors manifest impaired sociability, while a partial and full agonist of the obligatory glycine co-agonist binding site on the NMDA receptor improved sociability in the Balb/c mouse strain. Because 2-methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor (mGluR), reduced self-grooming behavior in BTBR T+tfJ (BTBR) mice, another inbred genetic mouse model of autism spectrum disorders (ASDs), and mGluR5 antagonism is emerging as an experimental treatment for the 'fragile X syndrome," which has a high prevalence of co-morbid ASDs, we examined the effects of MPEP on sociability and stereotypic behaviors in Balb/c and Swiss Webster mice in a standard paradigm. MPEP had complex effects on sociability, impairing some measures of sociability in both strains, while it reduced the intensity of some spontaneous measures of stereotypic behaviors emerging during free social interaction in Swiss Webster mice. Conceivably, mGluR5 antagonism exacerbates diminished endogenous tone of NMDA receptor-mediated neurotransmission in neural circuits relevant to at least some measures of sociability in Balb/c mice; the mGluR5 receptor contributes to regulation of the phosphorylation status of the NMDA receptor. In any event, although stereotypies are an important therapeutic target in ASDs, medication strategies to attenuate their severity via antagonism of mGluR5 receptors must be pursued cautiously because of their potential to worsen at least some measures of sociability.
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PMID:Complex effects of mGluR5 antagonism on sociability and stereotypic behaviors in mice: possible implications for the pharmacotherapy of autism spectrum disorders. 2184 Mar 81

Animal studies elucidating the neurobiology of fragile X syndrome (FXS) have led to multiple controlled trials in humans, with the Aberrant Behavior Checklist-Community (ABC-C) commonly adopted as a primary outcome measure. A multi-site collaboration examined the psychometric properties of the ABC-C in 630 individuals (ages 3-25) with FXS using exploratory and confirmatory factor analysis. Results support a six-factor structure, with one factor unchanged (Inappropriate Speech), four modified (Irritability, Hyperactivity, Lethargy/Withdrawal, and Stereotypy), and a new Social Avoidance factor. A comparison with ABC-C data from individuals with general intellectual disability and a list of commonly endorsed items are also reported. Reformulated ABC-C scores based on this FXS-specific factor structure may provide added outcome measure specificity and sensitivity in FXS clinical trials.
J Autism Dev Disord 2012 Jul
PMID:Psychometric study of the Aberrant Behavior Checklist in Fragile X Syndrome and implications for targeted treatment. 2197 17

The autistic phenotype in Down syndrome (DS) is marked by a characteristic pattern of stereotypies, anxiety and social withdrawal. Our aim was to study adaptive behaviour in DS with and without autistic comorbidity using the Vineland Adaptive Behaviour Scales (VABS), the Childhood Autism Rating Scales (CARS) and the DSM IV-TR criteria. We assessed 24 individuals and established three groups: Down syndrome (DS), DS and autistic disorder (DS-AD), and autistic disorder (AD). The DS and DS-AD groups showed statistically significantly similar strengths on the VABS (in receptive and domestic skills). The DS and DS-AD subjects also showed similar strengths on the CARS (in imitation and relating), differing significantly from the AD group. The profile of adaptive functioning and symptoms in DS-AD seemed to be more similar to that found in DS than to the profile emerging in AD. We suggest that the comorbidity of austistic symptoms in DS hampered the acquisition of adaptive skills more than did the presence of DS alone.
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PMID:The autistic phenotype in Down syndrome: differences in adaptive behaviour versus Down syndrome alone and autistic disorder alone. 2215 36

Balb/c mice are a model of impaired sociability and social motivation relevant to autism spectrum disorders (ASDs). Impaired sociability of 8-week old Balb/c mice is attenuated by agonists of the glycine(B) site on the NMDA receptor, such as d-cycloserine. Although ASDs are often recognized in toddlerhood, there is interest in earlier identification (e.g., before 6 months) and disease-modifying interventions to improve functional outcomes. Thus, we wondered if d-cycloserine could improve sociability in 4-week old Balb/c mice, similar to its effects in 8-week old mice. d-Cycloserine improved measures of impaired sociability in 4-week old (i.e., one-week post-weanling) Balb/c mice. Moreover, because stereotypies can compete with the salience of social stimuli, we compared Balb/c and Swiss Webster mice on several spontaneous stereotypic behaviors emerging during social interaction with a social stimulus mouse. Interestingly, similar to 8-week old mice, spontaneous stereotypic behaviors during social interaction were more intense in the 4-week old Swiss Webster mice; furthermore, d-cycloserine reduced their intensity. Thus, d-cycloserine improves both sociability and stereotypic behaviors, but these effects may lack strain-selectivity. A prosocial effect of d-cycloserine was observed at a dose as low as 32.0mg/kg in Balb/c mice. d-cycloserine has the therapeutic properties of a desired medication for ASDs; specifically, a medication should not improve stereotypic behaviors at the expense of worsening sociability and vice versa. The data suggest that targeting the NMDA receptor can have promising therapeutic effects on two prominent domains of psychopathology in ASDs: impaired sociability and spontaneous stereotypic behaviors.
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PMID:D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice. 2226 Dec 49


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