SEARCH · PubMed Health

Results for “Autism Spectrum Disorder”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed2005

Higher plasma ACTH levels in adults with Asperger syndrome.

OBJECTIVE: The aim of this preliminary study was to characterize the levels of plasma adrenocorticotropic hormone (ACTH) and cortisol in adult patients with Asperger syndrome (AS). METHODS: Twenty medication-free individuals with high-functioning AS were recruited from a clinic specialized in autism spectrum disorders. Ten age-matched healthy persons (hospital staff or students) with no neuropsychiatric disorders served as controls. Blood samples for the assessment were collected at 8:00 a.m. RESULTS: The patients with AS had significantly higher plasma-ACTH values than did the healthy controls. Plasma-cortisol levels were similar in both groups. CONCLUSION: Increased plasma-ACTH levels are associated with AS. Future studies are needed to clarify whether this finding is a biological consequence of chronic anxiety and elevated stress, or a sign of facilitated response to an acute novel stressor.

Adolescent↗

PubMed2006

Pten regulates neuronal arborization and social interaction in mice.

CNS deletion of Pten in the mouse has revealed its roles in controlling cell size and number, thus providing compelling etiology for macrocephaly and Lhermitte-Duclos disease. PTEN mutations in individuals with autism spectrum disorders (ASD) have also been reported, although a causal link between PTEN and ASD remains unclear. In the present study, we deleted Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus of mice. Resulting mutant mice showed abnormal social interaction and exaggerated responses to sensory stimuli. We observed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axonal tracts with increased synapses. This abnormal morphology was associated with activation of the Akt/mTor/S6k pathway and inactivation of Gsk3beta. Thus, our data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.

Animals↗

PubMed2006

Executive processes in Asperger syndrome: patterns of performance in a multiple case series.

Mixed evidence exists for executive dysfunction in autism spectrum disorders (ASD). This may be because of the nature of the tasks used, the heterogeneity of participants, and difficulties with recruiting appropriate control groups. A comprehensive battery of 'executive' tests was administered to 22 individuals with Asperger syndrome and 22 well-matched controls. Performance was analysed both between groups and on an individual basis to identify outliers in both the ASD and control groups. There were no differences between the groups on all 'classical' tests of executive function. However, differences were found on newer tests of executive function. Specifically, deficits in planning, abstract problem solving and especially multitasking. On the tests that discriminated the groups, all of the ASD individuals except one were identified as significantly impaired (i.e. below the 5th percentile of the control mean) on at least one executive measure. This study provides evidence for significant executive dysfunction in Asperger syndrome. Greatest dysfunction appeared in response initiation and intentionality at the highest level--the ability to engage and disengage actions in the service of overarching goals. These deficits are best observed through using more recent, ecologically valid tests of executive dysfunction. Moreover, performance on these measures correlated with autistic symptomatology.

Adolescent↗

PubMed2006

Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action.

BACKGROUND: Valproic acid (VPA) exposure in utero has been associated with an increased risk of both neural tube defects and autism spectrum disorders (ASDs). The terata induced by VPA suggest interference with pattern formation. Retinoic acid produces similar terata and is known to act in part by increasing the expression of Hoxa1. We tested the hypotheses that exposure to VPA would alter the expression of Hoxa1 in rat embryos during times of normal Hoxa1 expression (d10.5-13.5) and that exposure at earlier and later stages would induce inappropriate expression. METHOD: Hoxa1 expression levels were determined by real-time PCR in individual embryos 1 h after exposure on gestational d10, 12, 13, 14, or 15. Additionally, teratogenic (4-yn-VPA) and nonteratogenic analogs of VPA (IE-VPA), retinoic acid (RA), and saline were compared for effects on Hoxa1 expression on d12. Embryos were allowed to develop for 1, 2, 4, 6, or 24 h, to follow the time course of effects. RESULTS: In utero exposure to VPA on gestational d10 and on d12-14 significantly increased the level of Hoxa1 expression compared to saline-exposed embryos at developmental ages prior to, during and after the normal expression period for this gene. On gestational d12, exposures to VPA and 4-yn-VPA significantly increased Hoxa1 expression at all sacrifice times, compared to saline-exposed embryos. RA significantly elevated Hoxa1 expression at all time points except 24-h post-treatment. The nonteratogenic VPA analog, IE-VPA, did not affect Hoxa1 expression. CONCLUSIONS: VPA and 4-yn-VPA exposures elevated Hoxa1 mRNA during its normal expression period and induced expression outside of the normal period. This may explain, in part, how VPA disrupts development.

Animals↗

PubMedDate not supplied

A comparison of intensive behavior analytic and eclectic treatments for young children with autism.

We compared the effects of three treatment approaches on preschool-age children with autism spectrum disorders. Twenty-nine children received intensive behavior analytic intervention (IBT; 1:1 adult:child ratio, 25-40 h per week). A comparison group (n=16) received intensive "eclectic" intervention (a combination of methods, 1:1 or 1:2 ratio, 30 h per week) in public special education classrooms (designated the AP group). A second comparison group (GP) comprised 16 children in non-intensive public early intervention programs (a combination of methods, small groups, 15 h per week). Independent examiners administered standardized tests of cognitive, language, and adaptive skills to children in all three groups at intake and about 14 months after treatment began. The groups were similar on key variables at intake. At follow-up, the IBT group had higher mean standard scores in all skill domains than the AP and GP groups. The differences were statistically significant for all domains except motor skills. There were no statistically significant differences between the mean scores of the AP and GP groups. Learning rates at follow-up were also substantially higher for children in the IBT group than for either of the other two groups. These findings are consistent with other research showing that IBT is considerably more efficacious than "eclectic" intervention.

Adaptation, Psychological↗

PubMed2005

Intuition and autism: a possible role for Von Economo neurons.

Von Economo neurons (VENs) are a recently evolved cell type which may be involved in the fast intuitive assessment of complex situations. As such, they could be part of the circuitry supporting human social networks. We propose that the VENs relay an output of fronto-insular and anterior cingulate cortex to the parts of frontal and temporal cortex associated with theory-of-mind, where fast intuitions are melded with slower, deliberative judgments. The VENs emerge mainly after birth and increase in number until age 4 yrs. We propose that in autism spectrum disorders the VENs fail to develop normally, and that this failure might be partially responsible for the associated social disabilities that result from faulty intuition.

Animals↗

PubMed2006

Seeing it differently: visual processing in autism.

Several recent behavioral and neuroimaging studies have documented an impairment in face processing in individuals with Autism Spectrum Disorder (ASD). It remains unknown, however, what underlying mechanism gives rise to this face processing difficulty. One theory suggests that the difficulty derives from a pervasive problem in social interaction and/or motivation. An alternative view proposes that the face-processing problem is not entirely social in nature and that a visual perceptual impairment might also contribute. The focus of this review is on this latter, perceptual perspective, documenting the psychological and neural alterations that might account for the face processing impairment. The available evidence suggests that perceptual alterations are present in ASD, independent of social function.

Autistic Disorder↗

PubMed2006

Autism, the superior temporal sulcus and social perception.

The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on recent brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. STS abnormalities are characterized by decreased gray matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomical and functional anomalies occurring during early brain development could constitute the first step in the cascade of neural dysfunction underlying ASD. We will focus this review on the STS, which has been highly implicated in social cognition. We will review recent data on the contribution of the STS to normal social cognition and review brain-imaging data implicating this area in ASD. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Animals↗

PubMed2006

Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005.

Autism spectrum disorders (ASDs) affect 1 in 166 births. Although electroencephalogram (EEG) abnormalities and clinical seizures may play a role in ASDs, the exact frequency of EEG abnormalities in an ASD population that has not had clinical seizures or prior abnormal EEGs is unknown. There is no current consensus on whether treatment of EEG abnormalities may influence development. This retrospective review of 24-hour ambulatory digital EEG data collected from 889 ASD patients presenting between 1996 and 2005 (with no known genetic conditions, brain malformations, prior medications, or clinical seizures) shows that 540 of 889 (60.7%) subjects had abnormal EEG epileptiform activity in sleep with no difference based on clinical regression. The most frequent sites of epileptiform abnormalities were localized over the right temporal region. Of 176 patients treated with valproic acid, 80 normalized on EEG and 30 more showed EEG improvement compared with the first EEG (average of 10.1 months to repeat EEG).

Adolescent↗

PubMed2004

The neural basis of hyperlexic reading: an FMRI case study.

Children with autism spectrum disorders in very rare cases display surprisingly advanced "hyperlexic" reading skills. Using functional magnetic resonance imaging (fMRI), we studied the neural basis of this precocious reading ability in a 9-year-old hyperlexic boy who reads 6 years in advance of his age. During covert reading, he demonstrated greater activity in the left inferior frontal and superior temporal cortices than both chronological age- and reading age-matched controls. Activity in the right inferior temporal sulcus was greater when compared to reading age-matched controls. These findings suggest that precocious reading is brought about by simultaneously drawing on both left hemisphere phonological and right hemisphere visual systems, reconciling the two prevailing, but seemingly contradictory, single hemisphere theories of hyperlexia. Hyperlexic reading is therefore associated with hyperactivation of the left superior temporal cortex, much in the same way as developmental dyslexia is associated with hypoactivation of this area.

Brain↗

PubMed2003

Social skills interventions for the autism spectrum: essential ingredients and a model curriculum.

This article outlines the ingredients the authors feel are critical to making social skills interventions successful for children with autism spectrum disorders. The authors described basic principles for teaching social skills that capitalize on the strengths of such children, while specifically addressing their deficits. The authors applied these widely used principles to group social skills intervention. In particular, social skills groups for children with ASD need to break down complex social behaviors into concrete steps and rules that can be memorized and practiced in a variety of settings. Abstract concepts must be made concrete through a variety of visual, tangible, "hands-on" activities that make socialization fun. Visual structure and predictable routines are essential. Also critical to the success of social skills intervention are instruction and activities that provide necessary support for the language abilities of the participants. A variety of learning opportunities must be used to teach the goals and skills most relevant to children with ASD. These skills must be integrated as intervention progresses. Furthermore, interactions that require the children to focus on peers create a positive social group culture. Within this culture and environment, self-awareness and positive self-esteem can be fostered. A behavior plan that specifies individual goals for group members and a specific system for delivering rewards should be included. Other important ingredients include generalization, which is encouraged through community outings, skill practice in more naturalistic settings, and collaboration with parents and teachers to work on skills outside the group intervention. Weekly therapy does little to change basic deficits of ASD unless there is daily practice and reinforcement of the skills being learned in more natural situations. The authors hope that outlining these principles and specific techniques will encourage more clinicians to offer social skills groups and thus increase their availability around the nation and world. Continued research and treatment for social skills is necessary to provide much needed empiric evidence to determine effectiveness of such interventions.

Adolescent↗

PubMed2004

Autism: a target of pharmacotherapies?

Autism is reaching epidemic proportions. The diagnosis can be made as early as 2 years of age, and autistic patients are expected to have a normal life span. Thus, in terms of the number of 'patient years', autism spectrum disorder (ASD) represents a market that is as large as that of the biggest neurological indication, Alzheimer's disease. However, despite the clear unmet medical need no effective treatment is yet available. This could be because the biology of ASD is not clearly understood and thus proper drug treatment has not been possible. However, significant advances are being made toward understanding the mechanisms of the disease. Here, we review the most recent preclinical advances in the hope that they will lead to a breakthrough in the near future.

Animals↗

PubMed2000

Teaching on-task and on-schedule behaviors to high-functioning children with autism via picture activity schedules.

The purpose of this investigation was to evaluate the effectiveness of a two-component teaching package (graduated guidance and visual activity schedules) in teaching young students with autism to increase on-task and on-schedule behavior. Four children enrolled in a resource-based classroom in a public elementary school served as participants. An A-B-A-B withdrawal design was used to evaluate the effectiveness of a picture activity schedule on the percentage of intervals scored as on-task and on-schedule. Generalization measures were taken on the percentage of intervals scored as on-task and on-schedule with novel activities. The results of the investigation indicate that (a) student performance rose to criterion levels upon introduction of the graduated guidance procedure, (b) student performance maintained when the picture activity book was available (Book Only) and dropped when the picture activity book was not available (No Book), and (c) student performance generalized to novel activities. The implications of these findings show the importance for future development and use of visual activity schedules to promote the independent functioning of students with autism spectrum disorders in their least restrictive environments.

Autistic Disorder↗

PubMed2002

Visual scanning of faces in autism.

The visual scanpaths of five high-functioning adult autistic males and five adult male controls were recorded using an infrared corneal reflection technique as they viewed photographs of human faces. Analyses of the scanpath data revealed marked differences in the scanpaths of the two groups. The autistic participants viewed nonfeature areas of the faces significantly more often and core feature areas of the faces (i.e., eyes, nose, and mouth) significantly less often than did control participants. Across both groups of participants, scanpaths generally did not differ as a function of the instructions given to the participants (i.e., "Please look at the faces in any manner you wish." vs. "Please identify the emotions portrayed in these faces."). Autistic participants showed a deficit in emotion recognition, but this effect was driven primarily by deficits in the recognition of fear. Collectively, these results indicate disorganized processing of face stimuli in autistic individuals and suggest a mechanism that may subserve the social information processing deficits that characterize autism spectrum disorders.

Adult↗

PubMed2003

Case report: Angelman syndrome in an individual with a small SMC(15) and paternal uniparental disomy: a case report with reference to the assessment of cognitive functioning and autistic symptomatology.

The case of a 15-year-old male with Angelman syndrome, paternal uniparental disomy of chromosome 15, and a small supernumerary marker chromosome is discussed. Assessment of cognitive functioning revealed an uneven profile of ability across different domains; in particular, receptive language ability was found to be superior to expressive language ability, whilst both gross and fine motor skills were found to be relatively well developed. Assessment using the Autism Diagnostic Observation Schedule showed very little evidence of autistic symptomatology. The patient showed an interest in social interaction and used a variety of methods to communicate, including some gestures and several single words. A clinical history revealed febrile convulsions during childhood but an absence of seizures in the previous 5 years. The patient was not hypopigmented, and height, weight, and head circumference were within the normal range for his age. The implications of these features are discussed in the context of previous work describing a milder phenotype in nondeletion cases of Angelman syndrome and work that has examined the prevalence of autism spectrum disorders amongst individuals with Angelman syndrome.

Adolescent↗

PubMed2004

Effects on communicative requesting and speech development of the Picture Exchange Communication System in children with characteristics of autism.

Few studies on augmentative and alternative communication (AAC) systems have addressed the potential for such systems to impact word utterances in children with autism spectrum disorders (ASD). The Picture Exchange Communication System (PECS) is an AAC system designed specifically to minimize difficulties with communication skills experienced by individuals with ASD. The current study examined the role of PECS in improving the number of words spoken, increasing the complexity and length of phrases, and decreasing the non-word vocalizations of three young children with ASD and developmental delays (DD) with related characteristics. Participants were taught Phases 1-4 of PECS (i.e., picture exchange, increased distance, picture discrimination, and sentence construction). The results indicated that PECS was mastered rapidly by the participants and word utterances increased in number of words and complexity of grammar.

Autistic Disorder↗

PubMed2005

Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development.

We identified homozygous truncating mutations in HOXA1 in three genetically isolated human populations. The resulting phenotype includes horizontal gaze abnormalities, deafness, facial weakness, hypoventilation, vascular malformations of the internal carotid arteries and cardiac outflow tract, mental retardation and autism spectrum disorder. This is the first report to our knowledge of viable homozygous truncating mutations in any human HOX gene and of a mendelian disorder resulting from mutations in a human HOX gene critical for development of the central nervous system.

Autistic Disorder↗

PubMed2026

Evidence supporting the role of GIGYF2 in synapse development and autism.

Autism spectrum disorder (ASD) is a heterogeneous condition in which genetically defined subtypes offered insights into underlying biological mechanisms and potential targeted treatments. Here, we investigate the clinical and pathogenic significance of GIGYF2 variants in ASD through an integrated approach combining clinical genetics, conditional knockout (cKO) mouse models, neurobiology, and molecular studies. Through targeted sequencing, large-scale genomic data analysis of neurodevelopmental disorder cohorts, and international collaborations, we identified ten affected individuals from eight families harboring de novo or dominantly inherited likely gene-disruptive (LGD) variants and 13 affected individuals from 13 families with de novo missense variants in GIGYF2. Clinical characterization of 16 probands with GIGYF2 variants revealed common features, including ASD, language problems, intellectual disability, and anxiety. In a Gigyf2 cKO mouse model, we observed pronounced autistic-like behaviors, cognitive deficits, and anxiety-like behaviors, mirroring phenotypes observed in affected individuals. Mechanistically, Gigyf2 deficiency disrupted synaptic homeostasis, as evidenced by altered spine density and miniature excitatory postsynaptic currents, and impaired IGF-1R/mTOR signaling, along with dysregulation of synapse-related genes such as Nrp2. Pharmacological inhibition of mTOR with rapamycin or Torin1, as well as Nrp2 knockdown rescued synaptic defects in Gigyf2 KO neurons. These findings define a novel ASD subtype associated with GIGYF2 variants and establish GIGYF2 as a key regulator of synaptic development and function, implicating GIGYF2 dysfunction in ASD pathogenesis and highlighting the IGF-1R/mTOR pathway as a potential therapeutic target for GIGYF2-related ASD subtype.

Journal Article↗