Factors affecting behavior and welfare of service dogs for children with autism spectrum disorder

The use of service dogs for children with autism spectrum disorder is a relatively new and growing assistance-dog application. The objectives of this article were to identify and describe the factors influencing an autism service dog's performance and the impact of this type of placement on the dog's welfare. A qualitative approach uses interview and observational data to characterize the dogs' behaviors and welfare with relevancy to the dogs' home environments. Identification of potential physical stressors included lack of rest or recovery time after working, unintentional maltreatment and prodding by children with autism, lack of predictability in daily routines, and insufficient opportunities for recreational activities. Results revealed that these dogs formed social relationships primarily with the parents and second with the children with autism. Failure to recognize and respond to the identified physical, emotional, and social needs can have serious impacts on the behavior, welfare, and performance of these autism service dogs, as well as parental satisfaction. As applications of service dogs expand to new domains, there is a need to assess and understand factors and variables affecting the relationship between family and service dog to ensure continued success of these programs.     

The reach-to-grasp movement in children with autism spectrum disorder

Autism is associated with a wide and complex array of neurobehavioural symptoms. Examination of the motor system offers a particularly appealing method for studying autism by providing information about this syndrome that is relatively immune to experimental influence. In this article, we considered the relationship between possible movement disturbance and symptoms of autism and introduced an experimental model that may be useful for rehabilitation and diagnostic purposes: the reach-to-grasp movement. Research is reviewed that characterizes kinematically the reach-to-grasp movement in children with autism compared with age-matched 'controls'. Unlike the age-matched children, autistic children showed differences in movement planning and execution, supporting the view that movement disturbances may play a part in the phenomenon of autism.     

Absence of contagious yawning in children with autism spectrum disorder

This study is the first to report the disturbance of contagious yawning in individuals with autism spectrum disorder (ASD). Twenty-four children with ASD as well as 25 age-matched typically developing (TD) children observed video clips of either yawning or control mouth movements. Yawning video clips elicited more yawns in TD children than in children with ASD, but the frequency of yawns did not differ between groups when they observed control video clips. Moreover, TD children yawned more during or after the yawn video clips than the control video clips, but the type of video clips did not affect the amount of yawning in children with ASD. Current results suggest that contagious yawning is impaired in ASD, which may relate to their impairment in empathy. It supports the claim that contagious yawning is based on the capacity for empathy.     

Abnormal adaptive face-coding mechanisms in children with autism spectrum disorder

In low-level vision, exquisite sensitivity to variation in luminance is achieved by adaptive mechanisms that adjust neural sensitivity to the prevailing luminance level. In high-level vision, adaptive mechanisms contribute to our remarkable ability to distinguish thousands of similar faces [1]. A clear example of this sort of adaptive coding is the face-identity aftereffect [2, 3, 4, 5], in which adaptation to a particular face biases perception toward the opposite identity. Here we investigated face adaptation in children with autism spectrum disorder (ASD) by asking them to discriminate between two face identities, with and without prior adaptation to opposite-identity faces. The ASD group discriminated the identities with the same precision as did the age- and ability-matched control group, showing that face identification per se was unimpaired. However, children with ASD showed significantly less adaptation than did their typical peers, with the amount of adaptation correlating significantly with current symptomatology, and face aftereffects of children with elevated symptoms only one third those of controls. These results show that although children with ASD can learn a simple discrimination between two identities, adaptive face-coding mechanisms are severely compromised, offering a new explanation for previously reported face-perception difficulties [6, 7, 8] and possibly for some of the core social deficits in ASD [9, 10].     

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder(ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment(SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.     

Urinary p-cresol is elevated in small children with severe autism spectrum disorder

Several studies have described in autistic patients an overgrowth of unusual gut bacterial strains, able to push the fermentation of tyrosine up to the formation of p-cresol. We compared levels of urinary p-cresol, measured by high-performance liquid chromatography–ultraviolet, in 59 matched case-control pairs. Urinary p-cresol was significantly elevated in autistic children smaller than 8 years of age (p?<?0.01), typically females (p?<?0.05), and more severely affected regardless of sex (p?<?0.05). Urinary cotinine measurements excluded smoking-related hydrocarbon contaminations as contributors to these differences. Hence, elevated urinary p-cresol may serve as a biomarker of autism liability in small children, especially females and more severely affected males.     

Mutations in the gene encoding CADM1 are associated with autism spectrum disorder

The unified idea on the molecular pathogenesis of Autism Spectrum Disorder (ASD) is still unknown although mutations in genes encoding neuroligins and SHANK3 have been shown in a small part of the patients. RA175/SynCAM1/CADM1(CADM1), a member of immunoglobulin superfamily, is another synaptic cell adhesion molecule. To clarify the idea that impaired synaptogenesis underlies the pathogenesis of ASD, we examined the relationship between mutations in the CADM1 gene and ASD. We found two missense mutations, C739A(H246N) and A755C(Y251S), in the CADM1 gene of male Caucasian ASD patients and their family members. Both mutations were located in the third immunoglobulin domain, which is essential for trans-active interaction. The mutated CADM1 exhibited less amount of high molecular weight with the matured oligosaccharide, defective trafficking to the cell surface, and more susceptibility to the cleavage and or degradation. Our findings provide key support for the unified idea that impaired synaptogenesis underlies the pathogenesis of ASD.     

Alterations of urinary perchlorate levels in euthyroid postpubertal children with autism spectrum disorder

BackgroundPerchlorates ClO₄(⁻) are known environmental and food contaminants that act as inhibitors of iodine uptake by the thyroid gland; however, information concerning their possible association with the development of autism spectrum disorder (ASD) is still missing. The current study is first presenting the alterations in perchlorate urine levels in euthyroid children with ASD.ObjectivesTo examine urinary perchlorates and iodides in euthyroid children diagnosed with ASD, compared to age-, and BMI-matched neurotypical controls, and to verify the association between these two ions in ASD.MethodsIons were determined in 24 h urine samples determined by ion chromatography–conductivity cell detection (IC-CD) and ion chromatography–pulsed amperometric detection (IC-PAD) techniques, respectively, in a total of 130 postpubertal euthyroid children with normal BMI (the mean age 14.46 years, SD = 1.32; the mean BMI 20.6, SD = 1.37), divided into age- and BMI-matched groups of ASD patients and neurotypical, healthy children (control).ResultsThe ASD group presented with significantly higher perchlorate urine levels than the controls (median = 1.05 μg/L, interquartile range(IQR) = 1.5 versus median = 0.09 μg/L, IQR = 0.097, respectively), as well as lower iodide urine levels (median = 100.2 μg/L, IQR = 37 versus median = 156.95 μg/L, IQR = 26.11, respectively). The ASD group presented significantly lower TSH and higher free thyroid hormone (fT4, fT3) levels than the controls. In regression analyses, perchlorate urine levels showed significant positive relationships with normal BMI values and serum TSH, and inverse relationships with serum fT4. Urinary iodide levels showed significant inverse relationships with BMI values. The absence of ASD was associated with decreased odds of perchlorate urine levels (OR = 0.012, 95 % confidence interval [CI] 0.0002−0.76), and increased odds of iodide urine levels (OR = 1.15, 95 %CI 1.05–1.27).ConclusionsASD may have an independent and significant impact on perchlorate as well as iodide levels in urine of euthyroid lean postpubertal children. Perchlorate levels do not appear to be directly associated with iodide levels in euthyroid children.     

Young children with autism spectrum disorder use predictive eye movements in action observation

Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goal-directed actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others’ actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand–object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS.     

Hair levels of heavy metals and essential elements in Chinese children with autism spectrum disorder

BackgroundDisproportional heavy metals and essential elements were reported in children with autism spectrum disorder (ASD) that is obscure in etiology. Inevitably, the association is biased by diet and environmental factors.MethodsFifty pairs, one with ASD and the other living together from the same special school with cerebral palsy (CP), were recruited in Hangzhou (China), aged from 2 to 11 years old (74.0 % male). All samples were divided into two subgroups: preschool-aged (2–5 years old) and school-aged (6–10 years old). Heavy metals (As, Hg, Pb) and essential elements (Al, Ca, Cu, Mg, Mn, Zn) in hair were quantified by inductively coupled plasma mass spectrometry analysis and flame atomic absorption spectroscopy.ResultsThe children with ASD generally had lower hair levels of Mn (ASD 0.124 μg/g, CP 0.332 μg/g, P = 0.001) compared to the children with CP. After stratification for age, there were no significant differences detected in preschool-aged group. In school-aged group, the results exhibited the children with ASD had higher hair Pb (1.485 μg/g, 0.690 μg/g, P = 0.007) and Cu/Zn ratio (0.092, 0.060, P = 0.003), while hair Hg (0.254 μg/g, 0.353 μg/g, P = 0.016)、Mn (0.089 μg/g, 0.385 μg/g, P = 0.002)、Mg (17.81 μg/g, 24.53 μg/g, P = 0.014) and Zn (100.15 μg/g, 135.83 μg/g, P = 0.007) showed an opposite pattern.ConclusionsThese results suggest an imbalance of Mn in Chinese children with ASD.     

Oxytocin plasma concentrations in children and adolescents with autism spectrum disorder: correlation with autistic symptomatology

Findings from research in animal models and humans have shown a clear role for the neuropeptide oxytocin (OT) on complex social behaviors. This is also true in the context of autism spectrum disorder (ASD). Previous studies on peripheral OT concentrations in children and young adults have reported conflicting results with the initial studies presenting mainly decreased OT plasma levels in ASD compared to healthy controls. Our study therefore aimed to further investigate changes in peripheral OT concentrations as a potential surrogate for the effects observed in the central nervous system (CNS) in ASD. OT plasma concentrations were assessed in 19 male children and adolescents with ASD, all with an IQ > 70 (age 10.7 ± 3.8 years), 17 healthy male children (age 13.6 ± 2.1 years) and 19 young male patients with attention deficit hyperactivity disorder (ADHD) as a clinical control group (age 10.4 ± 1.9 years) using a validated radioimmunoassay. Analysis of covariance revealed significant group differences in OT plasma concentrations (F(2, 48) = 9.574, p < 0.001, η ² = 0.285; plasma concentrations ASD 19.61 ± 7.12 pg/ml, ADHD 8.05 ± 5.49 pg/ml, healthy controls 14.43 ± 9.64 pg/ml). Post hoc analyses showed significantly higher concentrations in children with ASD compared to ADHD (p < 0.001). After Bonferroni correction, there was no significant difference in ASD in comparison with healthy controls (p = 0.132). A significant strong correlation between plasma OT and autistic symptomatology, assessed by the Autism Diagnostic Observation Schedule, was observed in the ASD group (p = 0.013, r = 0.603). Patients with ADHD differed from healthy control children by significantly decreased OT concentrations (p = 0.014). No significant influences of the covariates age, IQ, medication and comorbidity could be seen. Our preliminary results point to a correlation of OT plasma concentrations with autistic symptom load in children with ASD and a modulation of the OT system also in the etiologically and phenotypically overlapping disorder ADHD. Further studies in humans and animal models are warranted to clarify the complex association of the OT system with social impairments as well as stress-related and depressive behavior and whether peripheral findings reflect primary changes of OT synthesis and/or release in relevant areas of the CNS.     

The cortisol awakening response (CAR) in male children with autism spectrum disorder

Our ability to adapt to change is fundamental. The cortisol awakening response (CAR) is a sharp rise in cortisol 30 min after waking to help prepare an individual for ensuing stress. Children with autism spectrum disorder (ASD) often have difficulty adapting to change. Exploration of the CAR is warranted; yet, the few studies investigating it are inconclusive. The CAR was investigated in 94 pre-pubertal male children 8-to-12 years of age with ASD (46) and typical development (TD, 48). Salivary samples were collected over three diurnal cycles involving two morning samples: M1: Immediately upon Waking and M2: 30-min Post Waking (M2 − M1 = CAR). The magnitude of the CAR was measured by independent two sample t-tests, variability was measured using Levene's Test, the sequence of the CAR was analyzed by a linear mixed-effects model and proportion of children exhibiting a CAR by chi-square test of independence. There were no significant differences on the CAR between the groups based on magnitude (t(92) = − 0.14, p = 0.89, d = 0.04), variability (F(45,47) = 1.11, p = 0.72, η² = 0.11) or the sequence over three days (F(2,88) = 0.26, p = 0.77, η² = 0.01). No significant differences were shown in the proportion of children exhibiting a CAR across the groups based on child (χ²(1) = 0.02, p = 0.89) or adult criterion (χ²(1) = 1.82, p = 0.18). Despite group differences in the regulation and responsivity of cortisol, the CAR is indistinguishable between children with and without ASD. Inconsistencies across studies may be due to age, criterion used, and diagnostic distinctions.     

Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder

Bornavirus infection occurs in many animals, including humans. However, the epidemiology of bornavirus in humans, especially children, is as yet unclear. Here, antibodies against bornaviruses in Japanese children with autism spectrum disorder (ASD) were evaluated using immunofluorescence analysis, western blotting and radio ligand assay. The prevalence of antibodies against bornavirus‐specific speckles, nucleoprotein and phosphoprotein were 22%, 48%, and 33%, respectively, in children with ASD. According to our criteria, the prevalence of antibodies against bornaviruses was 7.4% in children with ASD. This is the first report of the serological prevalence of bornavirus in Japanese children. Our results provide valuable baseline‐data for future studies regarding bornavirus epidemiology in children.

     

Genetic testing and genetic counseling among medicaid-enrolled children with autism spectrum disorder in 2001 and 2007

The rise in the prevalence of autism spectrum disorder (ASD) has resulted in increased efforts to understand the causes of this complex set of disorders that emerge early in childhood. Although research in this area is underway and yielding useful, but complex information about ASD, guidelines for the use of genetic testing and counseling among children with ASD conflict. The purpose of this study was to determine the frequency of use of genetic testing and counseling before the widespread implementation of clinical chromosomal microarray (CMA) to establish a baseline for the use of both services and to investigate potential disparities in the use of both services among children with ASD. We found that about two-thirds of children with ASD received genetic testing or counseling and the use of both services is increasing with time, even in the pre-CMA era. Being female and having a comorbid intellectual disability diagnosis both increased the likelihood of receiving genetic testing and genetic counseling. Initial discrepancies in the use of both services based on race/ethnicity suggest that troubling disparities observed in other services delivered to children with ASD and other mental health disorders persist in genetic testing and counseling as well. These results should incentivize further investigation of the impact of genetic testing and counseling on children with ASD and their families, and should drive efforts to explore and confront disparities in the delivery of these services, particularly with the advancing scientific research on this topic.     

The impact of educational rewards on the diagnosis of autism spectrum disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social interactions and communication. The prevalence of ASD has risen dramatically in recent years, but the underlying factors leading to this rise are not clear. In this paper, we test whether changes in state-level educational policy that impact school-level resources are associated with the rise in ASD diagnostic prevalence. Early identification of ASD can improve an array of outcomes for children, and school systems play an important role with identification of the condition. It is plausible that children attending schools with better resources from state governments are more likely to receive an ASD diagnosis and presumably appropriate services. We focus on one educational policy in particular, state-level rewards, which consist of a monetary transfer from state governments to school districts. To test the impact of educational rewards on ASD diagnosis, we rely on policy variation across states and time and estimate both two-way fixed effects (TWFE) models alongside recently advanced methods in the difference-in-differences (DiD) literature. Under a baseline TWFE specification we estimate that rewards policies are associated with a 18.46% increase in ASD diagnosis. Further, using DiD methods that account for bias in settings of differential policy timing, we find that the magnitude of the effect increases to 24.8%. We believe these findings to be suggestive evidence that educational rewards policies improved the likelihood of detection and diagnosis of ASD.     

Trace elements in children with autism spectrum disorder: A meta-analysis based on case-control studies

Autism spectrum disorder (ASD) is a common childhood neurodevelopmental disorder that may be related to trace elements. However, reports on the relationship between them are still inconsistent. In this article, we conducted a meta-analysis on this issue. We searched the PubMed, EMBASE, and Cochrane databases as of November 15, 2019. A random-effects model was used, and subgroups of studies were analyzed using samples of different measurements. Twenty-two original articles were identified (18 trace elements, including a total of 1014 children with ASD and 999 healthy controls). In autistic children, the overall levels of barium (Ba), mercury (Hg), lithium (Li), and lead (Pb) were higher. There were significant differences in the levels of copper (Cu) in the hair and serum between autistic children and the control group. The levels of Hg, Li, Pb and selenium (Se) in the hair of autistic children were higher than those of healthy children, while the levels of zinc (Zn) in the blood were lower. Excessive exposure to toxic heavy metals and inadequate intake of essential metal elements may be associated with ASD. Preventing excessive exposure to toxic metals and correcting poor dietary behaviors may be beneficial for the prevention and treatment of the disease.     

Disruption of neurexin 1 associated with autism spectrum disorder

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ~750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD.     

Structural variation of chromosomes in autism spectrum disorder

Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 unbalanced CNVs in 44% of ASD families not present in 500 controls (and re-examined in another 1152 controls). Karyotyping detected additional balanced changes. Although most variants were inherited, we found a total of 27 cases with de novo alterations, and in three (11%) of these individuals, two or more new variants were observed. De novo CNVs were found in approximately 7% and approximately 2% of idiopathic families having one child, or two or more ASD siblings, respectively. We also detected 13 loci with recurrent/overlapping CNV in unrelated cases, and at these sites, deletions and duplications affecting the same gene(s) in different individuals and sometimes in asymptomatic carriers were also found. Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility. Our most compelling result discovered CNV at 16p11.2 (p = 0.002) (with characteristics of a genomic disorder) at approximately 1% frequency. Some of the ASD regions were also common to mental retardation loci. Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup.