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1.  Autism in Developing Countries: Lessons from Iran 
Autism Research and Treatment  2011;2011:145359.
Most research into Autism Spectrum Disorders has been conducted in affluent English-speaking countries which have extensive professional support services. This paper describes a series of investigations that was undertaken in Iran, and these findings, together with reviews of research in other low-income countries, are used to identify key lessons in three areas of service provision of particular relevance to developing countries with scarce professional resources: first, the issues to be considered in establishing the prevalence of the condition nationally; second, identification of parental understanding of ASD and the impact it has on them as carers; third, the education and training that could be provided to families when professional supports are sparse. It is concluded that culturally sensitive, parental support strategies must be central to the planning and development of services. Moreover, future research should further elucidate the needs of families and evaluate the impact of culturally tailored interventions designed to promote the children's development and overall family quality of life.
PMCID: PMC3420542  PMID: 22937242
2.  Associations between Parental Anxiety/Depression and Child Behavior Problems Related to Autism Spectrum Disorders: The Roles of Parenting Stress and Parenting Self-Efficacy 
Autism Research and Treatment  2011;2011:395190.
Parents of children with autism spectrum disorders (ASDs) have been shown to experience increases in stress, depression, and anxiety, which are also associated with child behavior problems related to ASDs. Literature-examining potential mechanisms that underlie the relationship of child behavior problems and parental anxiety/depression in this population are scarce. The current study sought to examine the roles of parenting stress and parenting self-efficacy as mediators between child behavior problems and parental anxiety/depression. Using a sample of 134 mothers, these potential mediators were tested. Hypotheses were supported, indicating that parenting stress mediated the relationship between child behavior problems and decreased parenting self-efficacy, and decreased parenting self-efficacy in turn partially mediated the relationship between parenting stress and increased depression/anxiety.
PMCID: PMC3420762  PMID: 22937246
3.  Intracellular and Extracellular Redox Status and Free Radical Generation in Primary Immune Cells from Children with Autism 
Autism Research and Treatment  2011;2012:986519.
The modulation of the redox microenvironment is an important regulator of immune cell activation and proliferation. To investigate immune cell redox status in autism we quantified the intracellular glutathione redox couple (GSH/GSSG) in resting peripheral blood mononuclear cells (PBMCs), activated monocytes and CD4 T cells and the extracellular cysteine/cystine redox couple in the plasma from 43 children with autism and 41 age-matched control children. Resting PBMCs and activated monocytes from children with autism exhibited significantly higher oxidized glutathione (GSSG) and percent oxidized glutathione equivalents and decreased glutathione redox status (GSH/GSSG). In activated CD4 T cells from children with autism, the percent oxidized glutathione equivalents were similarly increased, and GSH and GSH/GSSG were decreased. In the plasma, both glutathione and cysteine redox ratios were decreased in autistic compared to control children. Consistent with decreased intracellular and extracellular redox status, generation of free radicals was significantly elevated in lymphocytes from the autistic children. These data indicate primary immune cells from autistic children have a more oxidized intracellular and extracellular microenvironment and a deficit in glutathione-mediated redox/antioxidant capacity compared to control children. These results suggest that the loss of glutathione redox homeostasis and chronic oxidative stress may contribute to immune dysregulation in autism.
PMCID: PMC3420377  PMID: 22928106
4.  Increasing the Understanding and Demonstration of Appropriate Affection in Children with Asperger Syndrome: A Pilot Trial 
Autism Research and Treatment  2011;2011:214317.
The study was conducted to examine relationships between affectionate behavior in children with Asperger syndrome and variables likely to influence its expression (e.g., tactile sensitivity, social ability). It also evaluated the impact of a cognitive behavioral intervention that aimed to improve a child's understanding and expression of affection. Twenty-one children, aged 7 to 12 years, participated in the trial. The results showed significant correlations between measures of affection and tactile sensitivity and social ability. After attending the 5-week program, parents identified significant increases in the appropriateness of children's affectionate behavior both towards immediate family and people outside the immediate family, despite reporting no significant changes in their child's general difficulties with affectionate behavior. There was a significant improvement in children's understanding of the purpose of affection. The findings are discussed as well as the limitations of the study.
PMCID: PMC3420448  PMID: 22937243
5.  Normal Gaze Cueing in Children with Autism Is Disrupted by Simultaneous Speech Utterances in “Live” Face-to-Face Interactions 
Autism Research and Treatment  2011;2011:545964.
Gaze cueing was assessed in children with autism and in typically developing children, using a computer-controlled “live” face-to-face procedure. Sensitivity to gaze direction was assessed using a Posner cuing paradigm. Both static and dynamic directional gaze cues were used. Consistent with many previous studies, using photographic and cartoon faces, gaze cueing was present in children with autism and was not developmentally delayed. However, in the same children, gaze cueing was abolished when a mouth movement occurred at the same time as the gaze cue. In contrast, typical children were able to use gaze cues in all conditions. The findings indicate that gaze cueing develops successfully in some children with autism but that their attention is disrupted by speech utterances. Their ability to learn to read nonverbal emotional and intentional signals provided by the eyes may therefore be significantly impaired. This may indicate a problem with cross-modal attention control or an abnormal sensitivity to peripheral motion in general or the mouth region in particular.
PMCID: PMC3420531  PMID: 22937251
6.  An Initial Investigation of the Generalization of a School-Based Social Competence Intervention for Youth with High-Functioning Autism 
Autism Research and Treatment  2011;2011:589539.
This study evaluated the impact of generalization of the Social Competence Intervention-Adolescent (SCI-A) curriculum in a school setting for individuals with high-functioning autism or Asperger's Syndrome (N = 6). This study examined to what degree the generalization of the SCI-A curriculum could be measured when delivered in a school setting. Across the six participants preliminary results suggest improvement on teacher reports of social skills and executive functioning. Some improvements were also evident in direct measures of facial-expression recognition. Data collected in the nonintervention settings indicated that some generalization of social interaction skills may have occurred for all six participants. Future research directions are discussed.
PMCID: PMC3420545  PMID: 22937252
7.  High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders 
Autism Research and Treatment  2011;2012:868576.
Autism spectrum disorders (ASDs) are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.
PMCID: PMC3420436  PMID: 22928102
8.  Association of Sensory Processing and Eating Problems in Children with Autism Spectrum Disorders 
Autism Research and Treatment  2011;2011:541926.
“Selective” or “picky eating” is a frequent problem in children with autism spectrum disorders (ASD). Many of these children do not treat sensory input, particularly olfactory, auditory, visual, and tactile information in the same manner as their typically developing peers of the same age. The purpose of this paper was to examine the relationship between problems of sensory processing and the number of eating problems in children with ASD. Of 95 children with ASD, 3 to 10 years of age, 65 percent showed a definite difference and 21 percent a probable difference in sensory processing on the total score of the Short Sensory Profile. These results were significantly related to an increase in the number of eating problems measured by the Eating Profile. These results could not be explained by age, sex, mental retardation, attention deficit disorder, or hyperactivity. Timely interventions focusing on the sensory components of eating must now be developed.
PMCID: PMC3420765  PMID: 22937249
9.  Parent Report of Community Psychiatric Comorbid Diagnoses in Autism Spectrum Disorders 
Autism Research and Treatment  2011;2011:405849.
We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD). Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-assigned lifetime psychiatric comorbidity were significantly higher with each additional year of life, with increasing autism severity, and with Asperger syndrome and pervasive developmental disorder—not otherwise specified compared with autistic disorder. Overall, in this largest study of parent-reported community diagnoses of psychiatric comorbidity, gender, autistic regression, autism severity, and type of ASD all emerged as significant factors correlating with cumulative prevalence. These findings could suggest both underlying trends in actual comorbidity as well as variation in community interpretation and application of comorbid diagnoses in ASD.
PMCID: PMC3420588  PMID: 22937248
10.  The Broader Autism Phenotype and Its Implications on the Etiology and Treatment of Autism Spectrum Disorders 
Autism Research and Treatment  2011;2011:545901.
The presence of autism-related traits has been well documented in undiagnosed family members of individuals with autism spectrum disorder (ASD). The most common finding is mild impairments in social and communication skills that are similar to those shown by individuals with autism, but exhibited to a lesser degree. Termed the broader autism phenotype (BAP), these traits suggest a genetic liability for autism-related traits in families. Genetic influence in autism is strong, with identical twins showing high concordance for the diagnosis and related traits and approximately 20% of all ASD cases having an identified genetic mechanism. This paper highlights the studies conducted to date regarding the BAP and considers the implications of these findings for the etiology and treatment of ASD.
PMCID: PMC3420416  PMID: 22937250
11.  Autism, Context/Noncontext Information Processing, and Atypical Development 
Autism Research and Treatment  2011;2011:681627.
Autism has been attributed to a deficit in contextual information processing. Attempts to understand autism in terms of such a defect, however, do not include more recent computational work upon context. This work has identified that context information processing depends upon the extraction and use of the information hidden in higher-order (or indirect) associations. Higher-order associations underlie the cognition of context rather than that of situations. This paper starts by examining the differences between higher-order and first-order (or direct) associations. Higher-order associations link entities not directly (as with first-order ones) but indirectly through all the connections they have via other entities. Extracting this information requires the processing of past episodes as a totality. As a result, this extraction depends upon specialised extraction processes separate from cognition. This information is then consolidated. Due to this difference, the extraction/consolidation of higher-order information can be impaired whilst cognition remains intact. Although not directly impaired, cognition will be indirectly impaired by knock on effects such as cognition compensating for absent higher-order information with information extracted from first-order associations. This paper discusses the implications of this for the inflexible, literal/immediate, and inappropriate information processing of autistic individuals.
PMCID: PMC3420794  PMID: 22937255
12.  Factors Affecting Age at Initial Autism Spectrum Disorder Diagnosis in a National Survey 
Autism Research and Treatment  2011;2011:874619.
Entry into early intervention depends on both age of first parent concern (AOC) and age at initial autism spectrum disorder (ASD) diagnosis (AOD). Using data collected from a national online registry from 6214 children diagnosed with an ASD between 1994 and 2010 in the US, we analyzed the effect of individual, family, and geographic covariates on AOC and AOD in a multivariate linear regression model with random effects. Overall, no single modifiable factor associated with AOC or AOD emerged but cumulative variation in certain individual- and family-based features, as well as some geographic factors, all contribute to AOC and AOD variation. A multipronged strategy is needed for targeted education and awareness campaigns to maximize outcomes and decrease disparities in ASD care.
PMCID: PMC3420379  PMID: 22937257
13.  Eye Movement Sequences during Simple versus Complex Information Processing of Scenes in Autism Spectrum Disorder 
Autism Research and Treatment  2011;2011:657383.
Minshew and Goldstein (1998) postulated that autism spectrum disorder (ASD) is a disorder of complex information processing. The current study was designed to investigate this hypothesis. Participants with and without ASD completed two scene perception tasks: a simple “spot the difference” task, where they had to say which one of a pair of pictures had a detail missing, and a complex “which one's weird” task, where they had to decide which one of a pair of pictures looks “weird”. Participants with ASD did not differ from TD participants in their ability to accurately identify the target picture in both tasks. However, analysis of the eye movement sequences showed that participants with ASD viewed scenes differently from normal controls exclusively for the complex task. This difference in eye movement patterns, and the method used to examine different patterns, adds to the knowledge base regarding eye movements and ASD. Our results are in accordance with Minshew and Goldstein's theory that complex, but not simple, information processing is impaired in ASD.
PMCID: PMC3420692  PMID: 22937254
14.  Possible Evidence for a Fall in the Prevalence of High-Functioning Pervasive Developmental Disorder with Age? 
Autism Research and Treatment  2011;2011:325495.
A survey was undertaken to investigate the prevalence of high-functioning pervasive developmental disorder (HFPDD) in a community sample of teenagers and adults aged 13 and above in the city of Sheffield, UK. 112 possible and definite cases were found, of whom 65 (57%) had a previous diagnosis. The detected prevalence of possible or definite HFPDD was found to be 0.24 per 1000 of the population of Sheffield city aged 13 or over, but the prevalence by year of age fell from a maximum of 1.1 per 1000 in the group aged 13 to 14 years old (1 young adult in every 900 in this age group) to 0.03 per 1000 in the over 60s (1 person in every 38500 in this age group). The results of this study are preliminary and need follow-up investigation in larger studies. We suggest several explanations for the findings, including reduced willingness to participate in a study as people get older, increased ascertainment in younger people, and increased mortality. Another contributory factor might be that the prevalence of high-functioning pervasive development disorder may decline with age. This raises the possibility that AS symptoms might become subclinical in adulthood in a proportion of people with HFPDD.
PMCID: PMC3420578  PMID: 22937245
15.  Developing a Deeper Understanding of Autism: Connecting Knowledge through Literature Mining 
Autism Research and Treatment  2011;2011:307152.
In the field of autism, an enormous increase in available information makes it very difficult to connect fragments of knowledge into a more coherent picture. We present a literature mining method, RaJoLink, to search for matched themes in unrelated literature that may contribute to a better understanding of complex pathological conditions, such as autism. 214 full text articles on autism, published in PubMed, served as a source of data. Using ontology construction, we identified the main concepts of what is already known about autism. Then, the RaJoLink method, based on Swanson's ABC model, was used to reveal potentially interesting, but not yet investigated, connections between different concepts in research. Among the more interesting concepts identified with RaJoLink in our study were calcineurin and NF-kappaB. Both terms can be linked to neuro-immune abnormalities in the brain of patients with autism. Further research is needed to provide stronger evidence about calcineurin and NF-kappaB involvement in autism. However, the analysis presented confirms that this method could support experts on their way towards discovering hidden relationships and towards a better understanding of the disorder.
PMCID: PMC3420468  PMID: 22937244
16.  Dysautonomia in Autism Spectrum Disorder: Case Reports of a Family with Review of the Literature 
Autism Research and Treatment  2011;2011:129795.
Case histories of a mother and her two children are reported. The mother was a recovered alcoholic. She and her two children, both of whom had symptoms that are typical of autistic spectrum disorder, had dysautonomia. All had intermittently abnormal erythrocyte transketolase studies indicating abnormal thiamine pyrophosphate homeostasis. Both children had unusual concentrations of urinary arsenic. All had symptomatic improvement with diet restriction and supplementary vitamin therapy but quickly relapsed after ingestion of sugar, milk, or wheat. The stress of a heavy metal burden, superimposed on existing genetic or epigenetic risk factors, may be important in the etiology of autism spectrum disorder when in combination. Dysautonomia has been associated with several diseases, including autism, without a common etiology. It is hypothesized that oxidative stress results in loss of cellular energy and causes retardation of hard wiring of the brain in infancy, affecting limbic system control of the autonomic nervous system.
PMCID: PMC3420600  PMID: 22937241
17.  The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications 
Autism Research and Treatment  2011;2011:398636.
Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.
PMCID: PMC3420760  PMID: 22937247
18.  Hypothesis: The Role of Sterols in Autism Spectrum Disorder 
Autism Research and Treatment  2011;2011:653570.
A possible role for sterols in the development of autism spectrum disorder (ASD) has not been proven, but studies in disorders of sterol biosynthesis, chiefly Smith-Lemli-Opitz syndrome (SLOS), enable hypotheses on a causal relationship to be discussed. Advances in genetic technology coupled with discoveries in membrane physiology have led to renewed interest for lipids in the nervous system. This paper hypothesizes on the role of sterol dysfunction in ASD through the framework of SLOS. Impaired sonic hedgehog patterning, alterations in membrane lipid rafts leading to abnormal synaptic plasticity, and impaired neurosteroid synthesis are discussed. Potential therapeutic agents include the development of neuroactive steroid-based agents and enzyme-specific drugs. Future investigations should reveal the specific mechanisms underlying sterol dysfunction in neurodevelopmental disorders by utilizing advanced imaging and molecular techniques.
PMCID: PMC3420784  PMID: 22937253
19.  Cognitive Skills of Young Children with and without Autism Spectrum Disorder Using the BSID-III 
Autism Research and Treatment  2011;2011:759289.
Objective. The purpose of the study was to compare the cognitive skills of young children diagnosed with autism spectrum disorder (ASD) to same-aged peers referred for possible developmental delays or behavioral concerns using the Bayley Scales of Infant Development-Third Edition. Method. A retrospective chart review was conducted of 147 children ages 16 to 38 months who were referred to a diagnostic clinic for developmental evaluation. Children with ASD were compared to those without ASD with respect to cognition and language outcomes, both overall and by age. Results. While language skills in children with ASD were more significantly delayed than language skills in children without ASD, there was less discrepancy in the cognitive skills of children with and without ASD. Conclusion. Formal cognitive assessment of children with ASD can provide guidance for developmental expectations and educational programming. Cognitive skills of children with ASD may be underappreciated.
PMCID: PMC3428618  PMID: 22937256

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