1. Camargo SP, Rispoli M, Ganz J, Hong ER, Davis H, Mason R. {{A Review of the Quality of Behaviorally-Based Intervention Research to Improve Social Interaction Skills of Children with ASD in Inclusive Settings}}. {J Autism Dev Disord}. 2014.
Students with autism spectrum disorders (ASDs) often have difficulties in social interaction skills, which may prevent their successful inclusion in general education placements. Behaviorally-based social skills interventions have been shown to be effective in attenuating such difficulties in these environments. In light of the increasing number of children with ASD being educated in inclusive settings and requirements for the use of research-based interventions in schools, this paper (1) analyzes the quality of single-case research using behaviorally-based interventions to improve social interaction skills of children with ASD in inclusive settings and (2) evaluates whether such interventions can be considered an evidence-based practice. Characteristics and components of the interventions are summarized, and their implications for practice and future research are discussed.
2. Carmeli E, Imam B. {{Health Promotion and Disease Prevention Strategies in Older Adults with Intellectual and Developmental Disabilities}}. {Front Public Health}. 2014; 2: 31.
The rapid growth in the number of individuals living with intellectual and developmental disabilities (IDD) along with their increased longevity present challenges to those concerned about health and well-being of this unique population. While much is known about health promotion and disease prevention in the general geriatric population, far less is known about those in older adults with IDD. Effective and efficient health promotion and disease prevention strategies need to be developed and implemented for improving the health and quality of life of older adults living with IDD. This is considered to be challenging given the continued shrinkage in the overall health care and welfare system services due to the cut in the governmental budget in some of the western countries. The ideal health promotion and disease prevention strategies for older adults with IDD should be tailored to the individuals’ health risks, address primary and secondary disease prevention, and prevent avoidable impairments that cause premature institutionalization. Domains of intervention should include cognitive, mental and physical health, accommodations, workplace considerations, assistive technology, recreational activities, and nutrition.
3. Casanova MF. {{Autism as a sequence: From heterochronic germinal cell divisions to abnormalities of cell migration and cortical dysplasias}}. {Med Hypotheses}. 2014.
The considerable heterogeneity in the number and severity of symptoms observed in autism spectrum disorders (ASD) has been regarded as an obstacle to any future research. Some authors believe that clinical heterogeneity results from the complex interplay of the many genetic and environmental factors that themselves define a condition as multifactorial. However, it is important to note that neuropathological findings in both idiopathic and syndromic autism suggests a single pathophysiological mechanism acting during brain development: the heterochronic division of germinal cells and subsequent migrational abnormalities of daughter cells to their target fields. Multiple exogenous (e.g., viruses, drugs) and endogenous (e.g., genetic mutations) factors are known to disrupt the division of germinal cells and provide for an autism phenotype. The variety of endogenous and exogenous factors, their timing of action during brain development, and the genetic susceptibility of affected individuals (a Triple Hit hypothesis) may all account for the clinical heterogeneity of ASD.
4. Corradi-Dell’acqua C, Schwartz S, Meaux E, Hubert B, Vuilleumier P, Deruelle C. {{Neural responses to emotional expression information in high- and low-spatial frequency in autism: evidence for a cortical dysfunction}}. {Front Hum Neurosci}. 2014; 8: 189.
Despite an overall consensus that Autism Spectrum Disorder (ASD) entails atypical processing of human faces and emotional expressions, the role of neural structures involved in early facial processing remains unresolved. An influential model for the neurotypical brain suggests that face processing in the fusiform gyrus and the amygdala is based on both high-spatial frequency (HSF) information carried by a parvocellular pathway, and low-spatial frequency (LSF) information separately conveyed by a magnocellular pathway. Here, we tested the fusiform gyrus and amygdala sensitivity to emotional face information conveyed by these distinct pathways in ASD individuals (and matched Controls). During functional Magnetical Resonance Imaging (fMRI), participants reported the apparent gender of hybrid face stimuli, made by merging two different faces (one in LSF and the other in HSF), out of which one displayed an emotional expression (fearful or happy) and the other was neutral. Controls exhibited increased fusiform activity to hybrid faces with an emotional expression (relative to hybrids composed only with neutral faces), regardless of whether this was conveyed by LSFs or HSFs in hybrid stimuli. ASD individuals showed intact fusiform response to LSF, but not HSF, expressions. Furthermore, the amygdala (and the ventral occipital cortex) was more sensitive to HSF than LSF expressions in Controls, but exhibited an opposite preference in ASD. Our data suggest spared LSF face processing in ASD, while cortical analysis of HSF expression cues appears affected. These findings converge with recent accounts suggesting that ASD might be characterized by a difficulty in integrating multiple local information and cause global processing troubles unexplained by losses in low spatial frequency inputs.
5. Cuesta-Vargas A, Gine-Garriga M. {{Development of a New Index of Balance in Adults with Intellectual and Developmental Disabilities}}. {PLoS One}. 2014; 9(5): e96529.
PURPOSES: The first objective was to propose a new model representing the balance level of adults with intellectual and developmental disabilities (IDD) using Principal Components Analysis (PCA); and the second objective was to use the results from the PCA recorded by regression method to construct and validate summative scales of the standardized values of the index, which may be useful to facilitate a balance assessment in adults with IDD. METHODS: A total of 801 individuals with IDD (509 males) mean 33.1+/-8.5 years old, were recruited from Special Olympic Games in Spain 2009 to 2012. The participants performed the following tests: the timed-stand test, the single leg stance test with open and closed eyes, the Functional Reach Test, the Expanded Timed-Get-up-and-Go Test. Data was analyzed using principal components analysis (PCA) with Oblimin rotation and Kaiser normalization. We examined the construct validity of our proposed two-factor model underlying balance for adults with IDD. The scores from PCA were recorded by regression method and were standardized. RESULTS: The Component Plot and Rotated Space indicated that a two-factor solution (Dynamic and Static Balance components) was optimal. The PCA with direct Oblimin rotation revealed a satisfactory percentage of total variance explained by the two factors: 51.6 and 21.4%, respectively. The median score standardized for component dynamic and static of the balance index for adults with IDD is shown how references values. CONCLUSIONS: Our study may lead to improvements in the understanding and assessment of balance in adults with IDD. First, it confirms that a two-factor model may underlie the balance construct, and second, it provides an index that may be useful for identifying the balance level for adults with IDD.
6. Gadow KD, Pinsonneault JK, Perlman G, Sadee W. {{Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder}}. {Res Dev Disabil}. 2014; 35(7): 1658-65.
The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3′-UTR 9/10 VNTR, rs27072 in the 3′-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on a priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents’ ratings) was associated with DAT1 intron8 (etap2=.063) and rs2283265 (etap2=.044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (etap2=.065) and depression (etap2=.059), and for DRD2 rs2283265, depression (etap2=.053). DRD2 rs2283265 was associated with teachers’ global ratings of ADHD (etap2=.052). DAT1 intron8 was associated with parent-rated hyperactivity (etap2=.045) and both DAT1 9/10 VNTR (etap2=.105) and DRD2 rs2283265 (etap2=.069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples.
7. Hodge D, Carollo TM, Lewin M, Hoffman CD, Sweeney DP. {{Sleep patterns in children with and without autism spectrum disorders: Developmental comparisons}}. {Res Dev Disabil}. 2014; 35(7): 1631-8.
The present study examined age-related changes in the sleep of children with autism spectrum disorders (ASD) compared to age-related changes in the sleep of typically developing (TD) children. Participants were 108 mothers of children with ASD and 108 mothers of TD children. Participants completed a questionnaire on children’s overall sleep quality that also tapped specific sleep-domains (i.e., bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, disordered breathing, daytime sleepiness). Results confirm significantly poorer sleep quantity and quality in children with ASD, particularly children age 6-9 years. Unlike TD children, the sleep problems of children with ASD were unlikely to diminish with age. Our findings suggest that it is important to exam specific domains of sleep as well as overall sleep patterns. Finding of significant age-related interactions suggests that the practice of combining children from wide age-ranges into a single category obfuscates potentially important developmental differences.
8. Khan A, Harney JW, Zavacki AM, Sajdel-Sulkowska EM. {{Disrupted brain thyroid hormone homeostasis and altered thyroid hormone-dependent brain gene expression in autism spectrum disorders}}. {J Physiol Pharmacol}. 2014; 65(2): 257-72.
The present study examined human postmortem brains for changes consistent with the hypothesis of local brain TH deficiency in autism spectrum disorders (ASD). Brain levels of oxidative stress marker – 3-nitrotyrosine (3-NT), iodothyronine deiodinase type 2(D2) and type 3 (D3), 3′,3,5-triiodothyronine (T3) content, mercury content and gene expression levels were analyzed and compared in the several regions of postmortem brains derived from both male and female control and ASD cases, age 4-16 years. We report that some parameters measured, such as D2 are subject to rapid postmortem inactivation, while others that were analyzed showed both brain region- and sex-dependent changes. Levels of 3-NT were overall increased, T3 was decreased in the cortical regions of ASD brains, while mercury levels measured only in the extracortical regions were not different. The expression of several thyroid hormone (TH)-dependent genes was altered in ASD. Data reported here suggest the possibility of brain region-specific disruption of TH homeostasis and gene expression in autism.
9. Kim DS, Ross PJ, Zaslavsky K, Ellis J. {{Optimizing neuronal differentiation from induced pluripotent stem cells to model ASD}}. {Front Cell Neurosci}. 2014; 8: 109.
Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder characterized by deficits in social communication, and restricted and repetitive patterns of behavior. Despite its high prevalence, discovery of pathophysiological mechanisms underlying ASD has lagged due to a lack of appropriate model systems. Recent advances in induced pluripotent stem cell (iPSC) technology and neural differentiation techniques allow for detailed functional analyses of neurons generated from living individuals with ASD. Refinement of cortical neuron differentiation methods from iPSCs will enable mechanistic studies of specific neuronal subpopulations that may be preferentially impaired in ASD. In this review, we summarize recent accomplishments in differentiation of cortical neurons from human pluripotent stems cells and efforts to establish in vitro model systems to study ASD using personalized neurons.
10. Manouilenko I, Eriksson JM, Humble MB, Bejerot S. {{Minor physical anomalies in adults with autism spectrum disorder and healthy controls}}. {Autism Res Treat}. 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.
11. Marques F, Brito MJ, Conde M, Pinto M, Moreira A. {{Autism spectrum disorder secondary to enterovirus encephalitis}}. {J Child Neurol}. 2014; 29(5): 708-14.
Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder.
12. Sampino S, Juszczak GR, Zacchini F, Swiergiel AH, Modlinski JA, Loi P, Ptak GE. {{Grand-paternal age and the development of autism-like symptoms in mice progeny}}. {Transl Psychiatry}. 2014; 4: e386.
Advanced paternal age (APA) contributes to the risk of autism spectrum disorders (ASDs) in children. In this study, we used a mouse model to investigate the effects of APA on behavioral features related to autistic syndromes (that is, social deficits, communication impairments and stereotypic/repetitive behaviors). We also examined whether such effects are transmitted across generations. To do this, males aged 15 months (APA) and 4 months (control) were bred with 4-month-old females, and the resulting offspring (F1) and their progeny (F2; conceived by 4-month-old parents) were tested for the presence and severity of ASD-like behaviors. Our results indicate that APA resulted in offspring that displayed distinctive symptoms of ASD. We found that both F1 conceived from old fathers and F2 derived from old grandfathers displayed increased ultrasound vocalization (USV) activity, decreased sociability, increased grooming activity and increased anxiety-like responses. Moreover, such abnormalities were partially transmitted to the second generation of mice, having APA grandfathers. In conclusion, our study suggests that the risk of ASD could develop over generations, consistent with heritable mutations and/or epigenetic alterations associated with APA.
13. Suliman R, Ben-David E, Shifman S. {{Chromatin regulators, phenotypic robustness, and autism risk}}. {Front Genet}. 2014; 5: 81.
Though extensively characterized clinically, the causes of autism spectrum disorder (ASD) remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD. However, it is unclear how it is possible for mutations in so many different genes to contribute to ASD. Recent findings suggest that many of the mutations disrupt genes involved in transcription regulation that are expressed prenatally in the developing brain. De novo disruptive mutations are also more frequent in girls with ASD, despite the fact that ASD is more prevalent in boys. In this paper, we hypothesize that loss of robustness may contribute to ASD. Loss of phenotypic robustness may be caused by mutations that disrupt capacitors that operate in the developing brain. This may lead to the release of cryptic genetic variation that contributes to ASD. Reduced robustness is consistent with the observed variability in expressivity and incomplete penetrance. It is also consistent with the hypothesis that the development of the female brain is more robust, and it may explain the higher rate and severity of disruptive de novo mutations in girls with ASD.
14. Zhang-James Y, Yang L, Middleton FA, Patak J, Faraone SV. {{Autism-related behavioral phenotypes in an Inbred Rat Substrain}}. {Behav Brain Res}. 2014.
Behavioral and genetic differences among Wistar-Kyoto (WKY) rats from different vendors and different breeders have long been observed, but generally overlooked. In our prior work, we found that two closely related WKY substrains, the WKY/NCrl and WKY/NHsd rats, differ in a small percentage of their genome which appeared to be highly enriched for autism risk genes. Although both substrains have been used widely in studies of hypertension, attention deficit/hyperactivity disorder (ADHD) and depression, they have not been tested for any autism-related behavioral phenotypes. Furthermore, these two substrains have often been used interchangeably in previous studies; no study has systematically examined the phenotypic differences that could be attributed by their small yet potentially meaningful genetic differences. In this paper we compared these two substrains on a battery of neurobehavioral tests. Although two substrains were similar in locomotor activity, WKY/NCrl rats were significantly different from WKY/NHsd rats in the elevated plus maze test, as well as measures of social interaction and ultrasonic vocalization. These strains were also compared with Sprague Dawley (SD) rats, a common outbred strain, and spontaneous hypertensive rats (SHR), an inbred rat model for ADHD and hypertension, which were derived from the same ancestor strain as the WKY strains. Our behavioral findings suggest that WKY/NCrl rats may be useful as a model autism spectrum disorders due to their lower social interest, lower ultrasonic vocalization and higher anxiety levels when WKY/NHsd rats are used as the control strain. Given the small genetic difference between the two inbred substrains, future studies to identify the exact gene and sequence variants that differ between the two may be useful for identifying the genetic mechanisms underlying these behaviors.
