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1.  Computer Vision Tools for Low-Cost and Noninvasive Measurement of Autism-Related Behaviors in Infants 
Autism Research and Treatment  2014;2014:935686.
The early detection of developmental disorders is key to child outcome, allowing interventions to be initiated which promote development and improve prognosis. Research on autism spectrum disorder (ASD) suggests that behavioral signs can be observed late in the first year of life. Many of these studies involve extensive frame-by-frame video observation and analysis of a child's natural behavior. Although nonintrusive, these methods are extremely time-intensive and require a high level of observer training; thus, they are burdensome for clinical and large population research purposes. This work is a first milestone in a long-term project on non-invasive early observation of children in order to aid in risk detection and research of neurodevelopmental disorders. We focus on providing low-cost computer vision tools to measure and identify ASD behavioral signs based on components of the Autism Observation Scale for Infants (AOSI). In particular, we develop algorithms to measure responses to general ASD risk assessment tasks and activities outlined by the AOSI which assess visual attention by tracking facial features. We show results, including comparisons with expert and nonexpert clinicians, which demonstrate that the proposed computer vision tools can capture critical behavioral observations and potentially augment the clinician's behavioral observations obtained from real in-clinic assessments.
doi:10.1155/2014/935686
PMCID: PMC4090521  PMID: 25045536
2.  Defining Autism: Variability in State Education Agency Definitions of and Evaluations for Autism Spectrum Disorders 
Autism Research and Treatment  2014;2014:327271.
In light of the steady rise in the prevalence of students with autism, this study examined the definition of autism published by state education agencies (SEAs), as well as SEA-indicated evaluation procedures for determining student qualification for autism. We compared components of each SEA definition to aspects of autism from two authoritative sources: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and Individuals with Disabilities Education Improvement Act (IDEA-2004). We also compared SEA-indicated evaluation procedures across SEAs to evaluation procedures noted in IDEA-2004. Results indicated that many more SEA definitions incorporate IDEA-2004 features than DSM-IV-TR features. However, despite similar foundations, SEA definitions of autism displayed considerable variability. Evaluation procedures were found to vary even more across SEAs. Moreover, within any particular SEA there often was little concordance between the definition (what autism is) and evaluation procedures (how autism is recognized). Recommendations for state and federal policy changes are discussed.
doi:10.1155/2014/327271
PMCID: PMC4060325  PMID: 24987527
3.  Parent Training Interventions for Toddlers with Autism Spectrum Disorder 
Autism Research and Treatment  2014;2014:839890.
Background. Now that early identification of toddlers with autism spectrum disorder (ASD) is possible, efforts are being made to develop interventions for children under three years of age. Most studies on early intervention have focused on intensive and individual interventions. However, parent training interventions that help parents interact and communicate with their toddlers with ASD might be a good alternative to promote the development of their child's sociocommunicative skills. Objective. This review aims to systematically examine (1) the use of parent training interventions for children with ASD under three years of age and (2) their effects on children's development, parents' well-being and parent-child interactions. Methods. Systematic searches were conducted to retrieve studies in which at least one parent was trained to implement ASD-specific techniques with their toddlers (0–36 months old) with a diagnosis of or suspected ASD. Results. Fifteen studies, involving 484 children (mean age: 23.26 months), were included in this review. Only two of them met criteria for conclusive evidence. Results show that parents were able to implement newly learned strategies and were generally very satisfied with parent training programs. However, findings pertaining to the children's communication and socioemotional skills, parent-child interactions, and parental well-being were inconclusive.
doi:10.1155/2014/839890
PMCID: PMC4033505  PMID: 24895534
4.  Characteristics of Children Who Lost the Diagnosis of Autism: A Sample from Istanbul, Turkey 
Autism Research and Treatment  2014;2014:472120.
Aim. The aim of this study was to describe a group of children who lost a diagnosis of autism following participation in early educational programs. Method. This is a descriptive study reporting the characteristics of children (n: 39) who lost their diagnosis of autism and explaining the educational programs that these children followed. The data were collected by reviewing the participants' files and through examinations. Results. All of the children were placed at regular psychiatric follow-ups. The mean age at referral was 2.39±0.75 years, whereas the mean age at the time of optimal outcome reported was 5.11 ± 1.95 years. Two of the children were in early intensive behavioral intervention (EIBI), and the rest were in a comprehensive naturalistic behavioral program. The childhood autism rating scale (CARS) total scores at baseline and final were 32.75 ± 3.15 and 18.01 ± 1.76, respectively. The mean IQ of the group at final examination was 116.70 ± 18.88. Conclusion. It could be concluded that a group of children with an autism diagnosis could lose the diagnosis of autism upon early intervention. High IQ and the development of communicative and language skills at an early age could be the most powerful factors contributing to an optimal outcome.
doi:10.1155/2014/472120
PMCID: PMC4022169  PMID: 24876961
5.  Recognition of Emotion from Facial Expressions with Direct or Averted Eye Gaze and Varying Expression Intensities in Children with Autism Disorder and Typically Developing Children 
Autism Research and Treatment  2014;2014:816137.
Eye gaze direction and expression intensity effects on emotion recognition in children with autism disorder and typically developing children were investigated. Children with autism disorder and typically developing children identified happy and angry expressions equally well. Children with autism disorder, however, were less accurate in identifying fear expressions across intensities and eye gaze directions. Children with autism disorder rated expressions with direct eyes, and 50% expressions, as more intense than typically developing children. A trend was also found for sad expressions, as children with autism disorder were less accurate in recognizing sadness at 100% intensity with direct eyes than typically developing children. Although the present research showed that children with autism disorder are sensitive to eye gaze direction, impairments in the recognition of fear, and possibly sadness, exist. Furthermore, children with autism disorder and typically developing children perceive the intensity of emotional expressions differently.
doi:10.1155/2014/816137
PMCID: PMC3996291  PMID: 24804098
6.  Minor Physical Anomalies in Adults with Autism Spectrum Disorder and Healthy Controls 
Autism Research and Treatment  2014;2014:743482.
Minor Physical Anomalies (MPAs) are subtle abnormalities of the head, face, and limbs, without significant cosmetic or functional impact to the individual. They are assumed to represent external markers of developmental deviations during foetal life. MPAs have been suggested to indicate severity in mental illness and constitute external markers for atypical brain development. Higher frequencies of MPAs can be found in children with autism. The aims of the present study were to examine the prevalence and patterns of MPAs in adults with autism spectrum disorder (ASD) and to investigate whether MPAs are associated with symptom severity and overall functioning. Fifty adults with ASD and intelligence within the normal range and 53 healthy controls were examined with the Waldrop scale, an instrument for assessing MPAs. Face and feet were photographed enabling blinded assessment. Significant differences between the ASD and the control group were found on the MPA total scores, and also in the craniofacial region scores. Moreover, the shape of the ears was associated with autistic traits, in the ASD group. High MPA total scores were associated with poorer functioning. The findings suggest a link between MPAs, autistic traits, and level of functioning. Assessment of MPAs may assist in the diagnostic procedure of psychiatric disorders.
doi:10.1155/2014/743482
PMCID: PMC3982266  PMID: 24782925
7.  Conceptualisation and Development of a Quality of Life Measure for Parents of Children with Autism Spectrum Disorder 
Autism Research and Treatment  2014;2014:160783.
Parents of children with autism spectrum disorder (ASD) tend to experience greater psychological distress than parents of typically developing children or children with other disabilities. Quality of Life (QoL) is increasingly recognised as a critical outcome measure for planning and treatment purposes in ASD. There is a need for ASD-specific QoL measures as generic measures may not capture all relevant aspects of living with ASD. This paper describes the conceptualisation and development of an autism-specific measure of QoL, the Quality of Life in Autism Questionnaire (QoLA) for parents and caregivers of children with ASD, that is suitable to clinical and research settings. Preliminary psychometric properties (reliability and validity) of the measure are also presented. The QoLA has 48 items in two subscales: one comprising QoL items and the second a parent report of how problematic their child's ASD symptoms are. A study involving 39 families suggested the QoLA has excellent internal consistency as well as good known-groups validity between parents of children with ASD and those who were typically developing. The QoLA also showed good convergent validity with other measures of QoL and ASD symptom severity, respectively. The QoLA may be a valuable assessment tool and merits further psychometric evaluation.
doi:10.1155/2014/160783
PMCID: PMC3977417  PMID: 24778873
8.  Measuring Outcome in an Early Intervention Program for Toddlers with Autism Spectrum Disorder: Use of a Curriculum-Based Assessment 
Autism Research and Treatment  2014;2014:964704.
Measuring progress of children with autism spectrum disorder (ASD) during intervention programs is a challenge faced by researchers and clinicians. Typically, standardized assessments of child development are used within research settings to measure the effects of early intervention programs. However, the use of standardized assessments is not without limitations, including lack of sensitivity of some assessments to measure small or slow progress, testing constraints that may affect the child's performance, and the lack of information provided by the assessments that can be used to guide treatment planning. The utility of a curriculum-based assessment is discussed in comparison to the use of standardized assessments to measure child functioning and progress throughout an early intervention program for toddlers with risk for ASD. Scores derived from the curriculum-based assessment were positively correlated with standardized assessments, captured progress masked by standardized assessments, and early scores were predictive of later outcomes. These results support the use of a curriculum-based assessment as an additional and appropriate method for measuring child progress in an early intervention program. Further benefits of the use of curriculum-based measures for use within community settings are discussed.
doi:10.1155/2014/964704
PMCID: PMC3966353  PMID: 24711926
9.  Potential Role of Selenoenzymes and Antioxidant Metabolism in relation to Autism Etiology and Pathology 
Autism Research and Treatment  2014;2014:164938.
Autism and autism spectrum disorders (ASDs) are behaviorally defined, but the biochemical pathogenesis of the underlying disease process remains uncharacterized. Studies indicate that antioxidant status is diminished in autistic subjects, suggesting its pathology is associated with augmented production of oxidative species and/or compromised antioxidant metabolism. This suggests ASD may result from defects in the metabolism of cellular antioxidants which maintain intracellular redox status by quenching reactive oxygen species (ROS). Selenium-dependent enzymes (selenoenzymes) are important in maintaining intercellular reducing conditions, particularly in the brain. Selenoenzymes are a family of ~25 genetically unique proteins, several of which have roles in preventing and reversing oxidative damage in brain and endocrine tissues. Since the brain's high rate of oxygen consumption is accompanied by high ROS production, selenoenzyme activities are particularly important in this tissue. Because selenoenzymes can be irreversibly inhibited by many electrophiles, exposure to these organic and inorganic agents can diminish selenoenzyme-dependent antioxidant functions. This can impair brain development, particularly via the adverse influence of oxidative stress on epigenetic regulation. Here we review the physiological roles of selenoproteins in relation to potential biochemical mechanisms of ASD etiology and pathology.
doi:10.1155/2014/164938
PMCID: PMC3966422  PMID: 24734177
10.  Disability Identification and Self-Efficacy among College Students on the Autism Spectrum 
Autism Research and Treatment  2014;2014:924182.
The number of youth on the autism spectrum approaching young adulthood and attending college is growing. Very little is known about the subjective experience of these college students. Disability identification and self-efficacy are two subjective factors that are critical for the developmental and logistical tasks associated with emerging adulthood. This study uses data from the National Longitudinal Transition Study 2 to examine the prevalence and correlates of disability identification and self-efficacy among college students on the autism spectrum. Results indicate nearly one-third of these students do not report seeing themselves as disabled or having a special need. Black race was associated with lower likelihood of both disability identification and self-efficacy.
doi:10.1155/2014/924182
PMCID: PMC3953486  PMID: 24707401
11.  The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case Control Study 
Autism Research and Treatment  2014;2014:242048.
Earlier reports showed the relationship between autism and immune genes located in the human leukocyte antigen (HLA). In this current study, we compared the HLA class I and class II alleles and haplotypes in 35 autistic children with 100 control subjects from Saudi Arabia, using PCR-SSP method and Luminex technology. In class I the HLA-A*01 (P = 0.03, OR 2.68), A*02 (P = 0.001, OR 3.02) and HLA-B*07 (P = 0.01, OR 3.27), were significantly associated with autism. Also, the haplotype A*02-B*07 was significantly higher in autistic patients than in controls (P = 0.007, OR 5.83). In class II, DRB1*1104 was significantly higher in patients than in controls (P = 0.001, OR 8.75). The DQB1*0202 (P = 0.001, OR 0.24), DQB1*0302 (P = 0.001, OR 0.14), and DQB1*0501 (P = 0.012, OR 0.25), were negatively associated with disease. While the four-loci genotype study showed that A*01-B*07-DRB1*0701-DQB1*0602 (P = 0.001, OR 41.9) and the A*31-B*51-DRB1*0103-DQB1*0302 (P = 0.012, OR 4.8) are positively associated with autism among Saudi patients. This is the first report on a foreseeable risk of association of HLA-B*07 allele with autism. Thus, HLA-B*07 allele and the closely linked haplotype A*01 B*07 DRB1*0701 DQB1*0602 may serve as a marker for genetic susceptibility to autism in Saudis.
doi:10.1155/2014/242048
PMCID: PMC3929985  PMID: 24672722
12.  No Differences in Emotion Recognition Strategies in Children with Autism Spectrum Disorder: Evidence from Hybrid Faces 
Autism Research and Treatment  2014;2014:345878.
Emotion recognition problems are frequently reported in individuals with an autism spectrum disorder (ASD). However, this research area is characterized by inconsistent findings, with atypical emotion processing strategies possibly contributing to existing contradictions. In addition, an attenuated saliency of the eyes region is often demonstrated in ASD during face identity processing. We wanted to compare reliance on mouth versus eyes information in children with and without ASD, using hybrid facial expressions. A group of six-to-eight-year-old boys with ASD and an age- and intelligence-matched typically developing (TD) group without intellectual disability performed an emotion labelling task with hybrid facial expressions. Five static expressions were used: one neutral expression and four emotional expressions, namely, anger, fear, happiness, and sadness. Hybrid faces were created, consisting of an emotional face half (upper or lower face region) with the other face half showing a neutral expression. Results showed no emotion recognition problem in ASD. Moreover, we provided evidence for the existence of top- and bottom-emotions in children: correct identification of expressions mainly depends on information in the eyes (so-called top-emotions: happiness) or in the mouth region (so-called bottom-emotions: sadness, anger, and fear). No stronger reliance on mouth information was found in children with ASD.
doi:10.1155/2014/345878
PMCID: PMC3909988  PMID: 24527213
13.  Dietary Intake and Plasma Levels of Choline and Betaine in Children with Autism Spectrum Disorders 
Autism Research and Treatment  2013;2013:578429.
Abnormalities in folate-dependent one-carbon metabolism have been reported in many children with autism. Because inadequate choline and betaine can negatively affect folate metabolism and in turn downstream methylation and antioxidant capacity, we sought to determine whether dietary intake of choline and betaine in children with autism was adequate to meet nutritional needs based on national recommendations. Three-day food records were analyzed for 288 children with autism (ASDs) who participated in the national Autism Intervention Research Network for Physical Health (AIR-P) Study on Diet and Nutrition in children with autism. Plasma concentrations of choline and betaine were measured in a subgroup of 35 children with ASDs and 32 age-matched control children. The results indicated that 60–93% of children with ASDs were consuming less than the recommended Adequate Intake (AI) for choline. Strong positive correlations were found between dietary intake and plasma concentrations of choline and betaine in autistic children as well as lower plasma concentrations compared to the control group. We conclude that choline and betaine intake is inadequate in a significant subgroup of children with ASDs and is reflected in lower plasma levels. Inadequate intake of choline and betaine may contribute to the metabolic abnormalities observed in many children with autism and warrants attention in nutritional counseling.
doi:10.1155/2013/578429
PMCID: PMC3876775  PMID: 24396597
14.  Utility of Teacher-Report Assessments of Autistic Severity in Japanese School Children 
Autism Research and Treatment  2013;2013:373240.
Recent studies suggest that many children with milder autism spectrum disorder (ASD) are undiagnosed, untreated, and being educated in mainstream classes without support and that school teachers might be the best persons to identify a child's social deviance. At present, only a few screening measures using teacher ratings of ASD have been validated. The aim of this study was to examine the utility of teacher ratings on the Social Responsiveness Scale (SRS), a quantitative measure of ASD. We recruited 130 participants aged 4 to 17 years from local schools or local pediatric outpatient clinics specializing in neurodevelopmental disorders that included 70 children with ASD. We found that the teacher-report SRS can be reliably and validly applied to children as a screening tool or for other research purposes, and it also has cross-cultural comparability. Although parent-teacher agreement was satisfactory overall, a discrepancy existed for children with ASD, especially for girls with ASD. To improve sensitivity in children at higher risk, especially girls, we cannot overstate the importance of using standardized norms specific to gender, informant, and culture.
doi:10.1155/2013/373240
PMCID: PMC3874348  PMID: 24392224
15.  Back to Basic: Do Children with Autism Spontaneously Look at Screen Displaying a Face or an Object? 
Autism Research and Treatment  2013;2013:835247.
Eye-tracking studies on exploration of faces and objects in autism provided important knowledge but only in a constraint condition (chin rest, total time looking at screen not reported), without studying potential differences between subjects with autism spectrum disorder (ASD) and controls in spontaneous visual attention toward a screen presenting these stimuli. This study used eye tracking to compare spontaneous visual attention to a screen displaying a face or an object between children with autism and controls in a nonconstraint condition and to investigate the relationship with clinical characteristics in autism group. Time exploring screen was measured during passive viewing of static images of faces or objects. Autistic behaviors were assessed by the CARS and the BSE-R in autism group. In autism group, time exploring face screen and time exploring object screen were lower than in controls and were not correlated with degree of distractibility. There was no interaction between group and type of image on time spent exploring screen. Only time exploring face screen was correlated with autism severity and gaze impairment. Results highlight particularities of spontaneous visual attention toward a screen displaying faces or objects in autism, which should be taken into account in future eye-tracking studies on face exploration.
doi:10.1155/2013/835247
PMCID: PMC3870651  PMID: 24382999
16.  The Michigan Autism Spectrum Questionnaire: A Rating Scale for High-Functioning Autism Spectrum Disorders 
Autism Research and Treatment  2013;2013:708273.
Although the DSM-5 has recently created a single category of autism spectrum disorder (ASD), delineation of its putative subtypes remains clinically useful. For this process, screening instruments should ideally be brief, simple, and easily available. The aim of this study is to describe the validity of one such instrument. We administered the Michigan Autism Spectrum Questionnaire (MASQ), a 10-item questionnaire, to 42 patients with ASD (age range 6–13 years, mean 9.7 years, SD 2.5, one female) and 18 patients with other psychiatric disorders (age range 6–17 years, mean 11.7 years, SD 3.8, 6 females). Responses to each item were scored from 0 to 4 yielding a total score of 30. Patients with intellectual disability were excluded. As a group, patients with ASD scored higher than those with other psychiatric disorders (Chi-square test with 1 df = 16.019, P < 0.0001). Within the ASD group, a linear discriminant analysis found that the best cut-off points were 22 or above for Asperger syndrome, 14 to 21 for autism/PDDNOS, and less than 14 for those with other psychiatric disorders. We propose that the MASQ can be used as a brief measure to screen high-functioning ASD from other psychiatric disorders and to identify its possible subtypes.
doi:10.1155/2013/708273
PMCID: PMC3870086  PMID: 24381759
17.  Awareness of Autism in Primary School Teachers 
Autism Research and Treatment  2013;2013:961595.
Objective. To assess the knowledge and perception of primary school teachers regarding autism in private and public schools of Karachi, Pakistan. Methods. A cross-sectional survey was conducted on primary school teachers in different districts of Karachi. A sample size of 170 teachers was selected by purposive sampling. Primary data was collected using self-administered questionnaires. These questions assessed the teacher's knowledge and perception of Autism. Data was entered on SPSS version 20. Frequencies and percentages were taken out for categorical variables. Results. Of the total 170 teachers, 85 were from the Private and 85 from Public sector schools. 55% (n = 94) of the teachers knew about Autism through the media and only 9% (n = 15) had formal training through workshops on Autism. 62% (n = 105) of the teachers were of the opinion that Autism is treatable. Majority of the teachers (57%) said that proper training is required for teaching autistic children. Conclusion. The knowledge related to Autism in our existing sample has mostly come from the media. Although we cannot undermine the role of media, there is a need to give formal training to teachers regarding the differentiating features of Autism, which in turn will aid in early diagnosis of the disease.
doi:10.1155/2013/961595
PMCID: PMC3864073  PMID: 24363934
18.  The Relationship between Comprehension of Figurative Language by Japanese Children with High Functioning Autism Spectrum Disorders and College Freshmen's Assessment of Its Conventionality of Usage 
Autism Research and Treatment  2013;2013:480635.
Unlike their English-speaking counterparts, Japanese children with high-functioning autism spectrum disorders (HFASDs) perform as well as typically developing (TD) children in comprehending metaphor, despite lacking 1st order theory of mind (ToM) reasoning. Additionally, although Japanese sarcasm and “indirect reproach” appear theoretically to need 2nd order ToM reasoning, HFASD children without this comprehended these forms of language as well as TD children. To attempt to explain this contradiction, we asked college freshmen to evaluate the strangeness (unconventionality) of these types of figurative language. We aimed to test the hypothesis that metaphor, sarcasm, and “indirect reproach” might be evaluated as more conventional than irony, which children with HFASDs do not comprehend as well as those with attention deficit hyperactivity disorder. The results for irony, metaphor, and “indirect reproach” supported the hypothesis, while those for sarcasm did not. Sarcasm is comprehended by HFASDs children as well as by TD children despite being evaluated as highly unconventional. This contradiction is discussed from a self-in-relation-to-other perspective. We postulate that a new explanation of disabilities of figurative language comprehension in children with HFASDs is needed instead of relying on a single cognitive process.
doi:10.1155/2013/480635
PMCID: PMC3830864  PMID: 24288607
19.  Effectiveness of Methylcobalamin and Folinic Acid Treatment on Adaptive Behavior in Children with Autistic Disorder Is Related to Glutathione Redox Status 
Autism Research and Treatment  2013;2013:609705.
Treatments targeting metabolic abnormalities in children with autism are limited. Previously we reported that a nutritional treatment significantly improved glutathione metabolism in children with autistic disorder. In this study we evaluated changes in adaptive behaviors in this cohort and determined whether such changes are related to changes in glutathione metabolism. Thirty-seven children diagnosed with autistic disorder and abnormal glutathione and methylation metabolism were treated with twice weekly 75 µg/Kg methylcobalamin and twice daily 400 µg folinic acid for 3 months in an open-label fashion. The Vineland Adaptive Behavior Scale (VABS) and glutathione redox metabolites were measured at baseline and at the end of the treatment period. Over the treatment period, all VABS subscales significantly improved with an average effect size of 0.59, and an average improvement in skills of 7.7 months. A greater improvement in glutathione redox status was associated with a greater improvement in expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills. Age, gender, and history of regression did not influence treatment response. The significant behavioral improvements observed and the relationship between these improvements to glutathione redox status suggest that nutritional interventions targeting redox metabolism may benefit some children with autism.
doi:10.1155/2013/609705
PMCID: PMC3810468  PMID: 24224089
20.  Parasympathetic Response Profiles Related to Social Functioning in Young Children with Autistic Disorder 
Autism Research and Treatment  2013;2013:868396.
Psychophysiology studies of heart rate and heart rate variability can be employed to study regulatory processes in children with autism. The objective of this study was to test for differences in respiratory sinus arrhythmia (RSA; a measure of heart rate variability) and to examine the relationship between physiologic responses and measures of social behavior. Participants included 2- to 6-year-old children with Autistic Disorder and children without autism. Heart rate and RSA were derived from ECG recordings made during a baseline period and then a stranger approach paradigm. Social and adaptive behavior was assessed by parent report. Groups did not differ in mean heart rate or RSA at baseline or in response to social challenge. However, children with autism were more likely to show a physiologic response to intrusive portions of the stranger approach than to less intrusive portions of this procedure. Nonautistic children were equally likely to respond to intrusive and less intrusive social events. Within the autistic group, physiologic response to the intrusive stranger approach corresponded to higher ratings of social adaptive behaviors. These results suggest that physiologic responses to social challenge may help understand differences in social behavioral outcomes in children with autism.
doi:10.1155/2013/868396
PMCID: PMC3794559  PMID: 24175094
21.  Neuropathology and Animal Models of Autism: Genetic and Environmental Factors 
Autism Research and Treatment  2013;2013:731935.
Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology.
doi:10.1155/2013/731935
PMCID: PMC3787615  PMID: 24151553
22.  Epigenetics and Autism 
Autism Research and Treatment  2013;2013:826156.
This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase Cβ1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs) associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals. These epigenetic mechanisms underlying male predominance, aberrant social interaction, and low functioning frontal cortex may be novel targets for autism prevention and treatment strategies.
doi:10.1155/2013/826156
PMCID: PMC3787640  PMID: 24151554
23.  Presence of Contagious Yawning in Children with Autism Spectrum Disorder 
Autism Research and Treatment  2013;2013:971686.
Most previous studies suggest diminished susceptibility to contagious yawning in children with autism spectrum disorder (ASD). However, it could be driven by their atypical attention to the face. To test this hypothesis, children with ASD and typically developing (TD) children were shown yawning and control movies. To ensure participants' attention to the face, an eye tracker controlled the onset of the yawning and control stimuli. Results demonstrated that both TD children and children with ASD yawned more frequently when they watched the yawning stimuli than the control stimuli. It is suggested therefore that the absence of contagious yawning in children with ASD, as reported in previous studies, might relate to their weaker tendency to spontaneously attend to others' faces.
doi:10.1155/2013/971686
PMCID: PMC3736493  PMID: 23970970
24.  Sensory Response Patterns in Nonverbal Children with ASD 
Autism Research and Treatment  2013;2013:436286.
We sought to examine concurrent and longitudinal associations between sensory response patterns (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) and verbal status of young children with autism spectrum disorder (ASD) as a potential factor influencing the development of verbal communication. Seventy-nine children with ASD (verbal, n = 29; nonverbal, n = 50) were assessed using cross-sectional analyses (Study 1), and 14 children with ASD (verbal, n = 6; nonverbal, n = 8) were assessed using prospective longitudinal analyses (Study 2). Data were collected regarding sensory response patterns and verbal ability. Hyporesponsiveness and sensory seeking behaviors were associated with verbal status in both cross-sectional and longitudinal analyses; nonverbal children were more likely to demonstrate higher hyporesponsive and sensory seeking patterns. Hyperresponsiveness did not significantly differ between verbal and nonverbal groups in either design. Sensory hyporesponsiveness and seeking behaviors may be important factors hindering the development of functional verbal communication in children with ASD. Unusual sensory responsiveness can often be observed before the onset of speech and may yield important prognostic capabilities as well as inform early interventions targeting verbal communication or alternative communication options in young children with ASD.
doi:10.1155/2013/436286
PMCID: PMC3727194  PMID: 23956859
25.  Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum Disorders 
Autism Research and Treatment  2013;2013:128264.
Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.
doi:10.1155/2013/128264
PMCID: PMC3687595  PMID: 23862063

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