Tackling the challenges of autism

"The Reason I Jump" by Naoki Higashida: A Reconsideration of Autism, Empathy, and “Mind-Blindness”

Neighborhood deprivation and childhood autism: A nationwide study from Sweden

IntroductionHypomelanotic skin disorders like tuberous sclerosis and hypomelanosis of Ito that present with multiple systemic manifestations have been reported in association with childhood autism. Oculocutaneous albinism is another hypomelanotic skin disorder that rarely presents with multiple systemic manifestations. It is infrequently reported in association with childhood autism when compared to tuberous sclerosis and hypomelanosis of Ito.Case presentationThis article reports a case of co-morbid childhood autism and oculocutaneous albinism in a 13-year old boy from Nigeria in Sub-Saharan Africa.ConclusionThe observation in this case report and in two previous reports which documented association between oculocutaneous albinism and childhood autism both in the affected individuals and families of individuals with childhood autism, raises the question of a possible genetic and clinical association between oculocutaneous albinism and childhood autism. More family and genetic studies into the relationship between oculocutaneous albinism and childhood autism is desirable. This may provide useful clues into the etiology, prevention and management of childhood autism as well as oculocutaneous albinism.

To explore the relationship between gene polymorphism of GABAA receptors and childhood autism by detecting rs140682, rs2081648 and rs140679 site of single nucleotide polymorphism (SNP) in GABAA receptors gene. A total of 94 children with autism and 124 normal children were enrolled in a hospital from November 2010 to May 2011. Childhood autism rating scale (CARS) and autism behavior checklist (ABC) were used to evaluate or investigate the case group. After collecting venous blood and extracting the genome DNA, the allele and genotype of SNP rs140682, rs2081648 and rs140679 site in GABAA receptors gene were detected by PCR-RFLP. The allele and genotype of case group and control group were analyzed by χ(2) test, while the score of scales was analyzed by Spearman rank correlation analysis. The age of the case group was 5.12 ± 0.32, and it was 5.25 ± 0.27 in the control group (P < 0.05). In case group, the frequency of genotype CC, CT and TT of rs140682 site was 44, 41 and 9, while it was 48, 65, and 11 in control group (P > 0.05), respectively. The frequency of genotype AA, AG and GG of rs2081648 site was 8, 58 and 28 in case group, while it was 12, 49 and 63 in control group (P < 0.05), respectively. In case group, the frequency of genotype CC, CT and TT of rs140679 site was 15, 36 and 43, while it was 18, 59 and 47 in control group (P > 0.05), respectively. It was revealed by Spearman rank correlation analysis that of rs2081648 site, there was a positive correlation between genotype AG and sensation factor (S), social intercourse factor (R), and language factor (L) of autism behavior checklist (ABC) (r values were 0.149, 0.165 and 0.155, all P values < 0.05). A negative correlation between genotype GG and S, R, L and self-help factor (V) was proved (r values were -0.140, -0.173, -0.158 and -0.135, all P values < 0.05). There was a positive correlation between allele A and R and L factors (r values were 0.153 and 0.137, all P values < 0.05), while a negative correlation between allele G and R and L factors (r values were -0.153 and -0.137, all P values < 0.05). In case group, 42 children were diagnosed with mild-to-moderate autism, while 52 children were severe autism. There was no statistically significant correlation between allele or genotype of SNP rs140682 and rs140679 site and the degree of autism (P > 0.05). There was a positive correlation between allele A and genotype AG and the degree of autism (r values were 0.147 and 0.616, all P values < 0.05), while a negative correlation between allele G and genotype GG and the degree of autism (r values were -0.159 and -0.616, all P values < 0.05). The SNP rs2081648 site which located in GABAA receptors gene may be related to autism. No evidence for significant association between rs140682 and rs140679 site and autism was found.

To investigate the cluster of differentiation 5 (CD5) plasma levels and their association with childhood autism rating scale (CARS) in subjects with autism spectrum disorder (ASD) compared to age and gender matched healthy controls, and to explore the link between CD5, severity, and autoimmunity in autism. Case-control study. Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2014 to May 2015. CD5 levels were determined in the plasma of thirty-one (31) patients using enzyme-linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) score and compared to thirty-three (33) age and gender-matched control samples. The preliminary data indicated that children with severe autism (n=12), exhibited significantly (p=0.02) higher plasma level of CD5 [0.55 (0.14-12) pg/ml {median (interquartile range=IQR)}] than those of normal controls [n=33, 0.29 (0.08-0.79) pg/ml {median (IQR)}] and children with mild to moderate autism [n=19, 0.26 (0.13-1.42) pg/ml, {median (IQR)}, p=0.08]. However, there was no significant difference between the CD5 levels of children with mild to moderate autism and normal controls (p = 0.62). Diagnoses of autistic children based on the CARS score >30. Disease severity and the CARS score, which represent stereotyped patterns of behavior in children with autism, were positively correlated (r = 0.43, p = 0.02). The high CD5 plasma levels in patients with severe ASD, probably indicated that CD5 might be implicated in the physiology of autism. However, this finding should be treated with caution until further investigations are performed with larger populations to determine whether the increase in plasma CD5 levels is a mere consequence of autism or it plays a pathogenic role in the disease.

Objective: The aim of the study is to screen the autism spectrum disorder (ASD) of children between the ages of 18 and 36 months in the county of Van, Ipekyolu, and examine the results in terms of some variables. Materials and methods: It is a cross-sectional study. The sample of the study consisted of 521 children between the ages of 18-36 months, who were brought to the family health centers in the central Ipekyolu district of Van between 01.04.2019-30-04.2019, who agreed to participate in the study, for vaccination and child surveillance. Modified Early Childhood Autism Screening Scale (M-CHAT) assessment test was used to screen children for ASD. Results: The average age of the children participating in the study is 26.61 ± 5.91 months. The average age of the mothers is 26.45 ± 3.39 and the average age of the fathers is 29.79 ± 3.24 years. The high risk of autism in boys was 9.1%, and this rate was 7.6% in girls. As the level of mother education increases, the frequency of the child being found to be at high risk for ASD decreases as a result of the test. The high risk of autism is 11.2% in cesarean delivery and 6.0% in normal delivery. High risk of autism was found higher in children born by cesarean section. While the high risk of autism is highest in the second (56.8%) children, it is the lowest in the third and fourth children (11.4%). The frequency of being found to be at high risk for autism has increased in those whose monthly income is above the minimum wage. There was no significant difference between gender, father education level, number of siblings, mother and father health status and M-CHAT results. According to the psychiatric examination, only 6 cases of 44 children who were found to be M-CHAT positive were diagnosed with autism. In children diagnosed with autism, the male / female ratio was found to be 5/1. As a result of the study, the prevalence of general autism was found 11.5 per thousand. Conclusion: When the data obtained in the study were evaluated, it was found that the incidence of ASD was higher than other studies in our country. For the early diagnosis of ASD, the detection of risky children with screening tests is important for the prognosis of the disease. Screening tests for children for the early diagnosis of ASD is important for the prognosis of the disease. It is necessary to identify children at risk of autism early and to support their development with early intervention programs, programs related to the subject and more comprehensive screening.

Objective To investigate the effects of normobaric hyperoxia intervention on learning and memory abilities of valproic acid(VPA) autism model rats and the morphology of pyramidal cells in hippocampus CA1 area. Methods Animal model groups of autism were obtained in male offspring of the Wistar rats that received intraperitoneal injection of 600 mg/kg VPA at the 12.5 day after pregnancy. According to the eye opening time, behavior, weaning weight and the learning and memory abilities which were evaluated by the Y electricity maze test at the 28th day after birth, 40 male VPA autism model rats were randomly selected 20 only and divided into normobaric hyperoxia model group(group A, n=10), atmospheric air model group(group B, n=10). Normal control groups were obtained in male offspring of Wistar rats that received intraperitoneal injection of equivalent physiological saline at the same period pregnancy.(group C, n=10). Rats in group A were treated with oxygen for 1h per day and lasted 1 week; group B and C were treated with normal air. The learning and memory abilities of three groups were assessed at the 35th day after birth. The immunohistochemistry methods and image analysis were used to observe the pyramidal cells of autism model rats in hippocampal CA1 region. The effect of normobaric hyperoxia therapy on pyramidal cell of autism model rats in hippocampal CA1 region were evaluated by HE staining technique. Results The trying times of group A after treatment were less than those before treatment (31.15±0.99 vs 31.54±0.97, t=2.739, P=0.018). The memory times were more than those before treatment(3.00±0.58 vs 2.69±0.48, t=-2.309, P=0.040). The trying times of group A after treatment were less than those in group B after treatment(P=0.016). The memory times of group A were not different from that in group B after treatment(P=0.810). The morphology of pyramidal cells in hippocampal CA1 region showed that the pyramidal cells of the autism model rats had apoptosised. The number of apoptotic cells reduced and the number of normal form cells increased after the normobaric hyperoxia intervention compared with the autism model rats. Conclusion Normobaric hyperoxia intervention can improve the learning and memory abilities of the autism model rats.The apoptosis of the pyramidal neurons in hippocampal CA1 might be reduced after the normobaric hyperoxia intervention. Key words: Valproate; Normobaric hyperoxia; Autism; Learning and memory; Hippocampus

This paper, written in honor of Professor Ed Zigler, focuses on some of the themes in developmental disabilities research that were so central to his work. It has now been nearly 80 years since Leo Kanner first identified the prototypic form - early infantile autism - of what is now autism spectrum disorder. In this article we summarize the development of the concept and the important accumulation of knowledge over time that has now led us to the recognition of a broader autism phenotype just as, at the same time, the current official diagnostic system in the USA has narrowed the concept. We also address current controversies regarding autism as the diagnosis is impacted by age and developmental factors, gender, and cultural issues. In parallel to the work on intellectual deficiency and development pioneered by Zigler and his colleagues, we summarize some of the challenges for the years ahead.

2. Muller RA, Shih P, Keehn B, Deyoe JR, Leyden KM, Shukla DK. Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders. Cereb Cortex. 2011 Oct;21(10):2233-43. 3. Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ. Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb Cortex 2007;17:951–61. 4. Kleinhans NM, Richards T, Sterling L, Stegbauer KC, Mahurin R, Johnson LC, Greenson J, Dawson G, Aylward E. Abnormal functional connectivity in autism spectrum disorders during face processing. Brain 2008;131:1000–12. 5. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. 2001. A default mode of brain function. Proc. Natl. Acad. Sci. USA 98:676–82 6. Weng SJ, Wiggins JL, Peltier SJ, Carrasco M, Risi S, Lord C, Monk CS. Alterations of resting state functional connectivity in the default network in adolescents with autism spectrum disorders. Brain Res. 2010 Feb 8;1313:202-14. 7. Monk CS, Peltier SJ, Wiggins JL, Weng SJ, Carrasco M, Risi S, Lord C. Abnormalities of intrinsic functional connectivity in autism spectrum disorders. Neuroimage 2009;47:764–772. 8. Dalton KM, BM Nacewicz, T Johnstone, HS Schaefer, MA Gernsbacher, HH Goldsmith, AL Alexander, and RJ Davidson. Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci; 2005. 8(4): p. 519-26 9. Wechsler D, Wechsler Abbreviated Scale of Intelligence (WASI). 4th ed. 1999, San Antonio, Tx: The Psychological Corporation. 10. Thesen, S., O. Heid, E. Mueller, and L.R. Schad, Prospective acquisition correction for head motion with image-based tracking for real-time fMRI. Magn Reson Med, 2000. 44(3): p. 457-65. 11. Behzadi, Y., Restom, K., Liau, J. and Liu, T.T. (2007) A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. NeuroImage, 37: 90-101. Resting State Functional Connectivity in Autism Spectrum Disorders: An fMRI Study!

Objective The aim of this study was to assess the plasma zinc (Zn)/serum copper (Cu) ratio as a biomarker in children with autism spectrum. Background Autism is a complex, behaviorally defined neurodevelopmental disorder characterized by significant impairments in social interaction, verbal and nonverbal communication, and restrictive, repetitive, and stereotypic patterns of behavior. The possible etiologies that precipitate autism symptoms remain controversial in many cases, but both genetic and environmental factors have been implicated. Children with autism spectrum disorder (ASD) appear to be at risk for Zn deficiency, Cu toxicity, and often have low Zn/Cu ratio. Patients and methods The present study was designed to be of a case–control type. It enrolled 40 children. Twenty patients with autism diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision and the Childhood Autism Rating Scales were included. The control group enrolled 20 apparently healthy children, matched to the patients' age and sex. All of them were subjected to biochemical analysis for assessment of plasma Zn level and serum Cu, followed by calculation of plasma Zn/serum Cu ratio. Results Plasma Zn was decreased in patients than in controls. Serum Cu was higher in patients than in controls. Lower Zn/Cu ratio was observed in cases in comparison with controls. intelligence quotient was lower in patients than in controls. There was a correlation between age and Zn/Cu ratio, but there was no correlation between Zn/Cu ratio and BMI. There was a negative correlation between Childhood Autism Rating Scales and Zn/Cu ratio. Zn/Cu correlated negatively with some selected symptom severity in autistic children and Zn/Cu ratio. According to receiver operating characteristic curve, the optimal cutoff value of serum levels of Zn/Cu was projected to be 0.81, with a sensitivity of 85% and a specificity of 85%, and the area under the curve was 0.93. Conclusion Our results suggested an association between blood levels of Zn and Cu with ASD among our patients, and the Zn/Cu ratio could be considered a biomarker of ASD.

To explore possible relationship between copy-number variations (CNVs) in 15q11-13, 16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification (MLPA) and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism. The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-IV, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains. Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANK3 microdeletion, accounting for approximately 2% (2/109) of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation. SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANK3 microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism.

Forty years after Kanner’s seminal article, experts continue to disagree about the definition, reliability and usefulness of the Early Infantile Autism (EIA) syndrome. The ongoing controversy is fuelled by misconceptions about the purpose of diagnosis, by the use of various diagnostic criteria and a failure to consider whether the EIA diagnosis is useful in a practical sense. In the present article, the EIA syndrome is examined from three perspectives. The first addresses the general question of whether identifying childhood psychotic syndromes is a worthwhile enterprise. Next, evidence for the reliability of the EIA syndrome is reviewed. Finally, the usefulness of considering EIA a discrete syndrome is examined. It is concluded that: (a) identifying syndromes of childhood psychosis is not only worthwhile but crucial for progress in research and treatment; (b) EIA can be reliably diagnosed and, (c) there is evidence supporting the usefulness of the EIA syndrome.

Morphometry, the measurement of forms, is an ancient practice. Recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of autism. Is the body, like the brain, affected by abnormal development in these patients? The aim of this study was to evaluate body mass index (BMI) of children with infantile autism, by comparing the BMI of 117 children with infantile autism with the corresponding BMI percentiles in an age- and sex-matched reference population. The BMI distribution of the male, but not female, children with infantile autism was significantly lower than that of the age-matched reference population. There was no evidence that BMI was associated with intelligence or socioeconomic status among children with infantile autism.

How do we come to the decision that we like a face? This thesis investigates this important aspect of social processing and communication by examining preference decisions for faces and the role that visual behavior plays in the process. I present a series of studies designed to investigate face preference formation and gaze patterns using eye-tracking and self-reported preference ratings. I tested healthy control subjects and two clinical populations known to have deficits in social processing: people with autism and patients with amygdala lesions. In studies one and two, I explore whether known social cognition deficits in people with autism and amygdala lesions also impair subjective decision-making regarding the attractiveness of faces. In study three, I investigate the flexibility of rule-based visual strategies used by these populations during face perception. Additionally, I present a custom algorithm developed to process raw eyetracking data, which was used to analyze all eyetracking data in this thesis. People with autism and patients with amygdala lesions are known to have general deficits in social processing, including difficulty orienting toward and evaluating faces. Nevertheless, I find that their behavior is markedly similar in many areas where we would expect them to have abnormalities or deficiencies. Their preference decisions when judging facial attractiveness were highly correlated with those made by controls, and both groups showed the same biases for familiar faces over novel faces. In addition, people with autism exhibit the same visual sampling behavior linking preference and attentional orienting, but reach their decisions faster than controls and also appear insensitive to the difficulty of the choice. Finally, gaze to the eye region appears normal in the absence of an explicit decision-making task, but only when analyzed in a similar manner as previous studies. However, when face sub-regions were analyzed in greater detail, people with autism demonstrate abnormalities in face gaze patterns, failing to emphasize the most information-rich regions of the face. Furthermore, people with autism demonstrate impairments in their ability to update those gaze patterns to accommodate different viewing restrictions. Taken together, these findings support the idea that the normal formation of face preferences can be preserved in the presence of general social processing impairments. Patterns in the eyetracking and behavioral data indicate that this is made possible, in part, by compensatory atypical processing and visual strategies.

Children with autism face many social challenges and these have been associated with vulnerability to social exclusion and higher levels of bullying compared to the general population. This can lead to long-term negative outcomes including damaged self-esteem and mental health difficulties. Since the majority of autistic children in the UK attend mainstream schools, the studies conducted for this thesis aimed to explore under-researched areas such as the impact of inclusion, and in particular the attitudes of neurotypical children towards their autistic peers. In Study 1, interviews with autistic girls and their parents (n=22) revealed that girls experienced high levels of bullying, school absenteeism and a tendency to mask their autism and that this was more apparent in mainstream compared to special schools. In Study 2, interviews with teachers (n=12) highlighted many challenges supporting autistic children, but also identified some creative solutions and factors that control the extent to which these were implemented. The next three studies explored attitudes of neurotypical children and whether these could be changed through exposure and contact. Studies 3 and 4 (n=775) investigated attitudes of children in schools with high versus low exposure to autism. Findings revealed that educational exposure led to an increase in prosocial emotional responses to bullying and increased personal exposure facilitated an increase in positive attitudes towards people with autism. Study 5 evaluated the influence of contact with autistic peers through group music-making (n=49) on the attitudes of their neurotypical peers. The intervention led to increased prosocial emotional responses to a vignette depicting social exclusion of a child with autism. In summary, autistic children face many challenges, which are not always addressed by teachers in mainstream schools. Furthermore, the physical and social environment of the school affects attitudes towards autistic children. Combining educational exposure within inclusive school climates, and personal exposure through structured intergroup opportunities, can improve responses to bullying and attitudes towards autism, and may ultimately increase quality of life for autistic children in mainstream schools.