1. Al-Hiyali MI, Yahya N, Faye I, Hussein AF. Identification of Autism Subtypes Based on Wavelet Coherence of BOLD FMRI Signals Using Convolutional Neural Network. Sensors (Basel, Switzerland). 2021; 21(16).

The functional connectivity (FC) patterns of resting-state functional magnetic resonance imaging (rs-fMRI) play an essential role in the development of autism spectrum disorders (ASD) classification models. There are available methods in literature that have used FC patterns as inputs for binary classification models, but the results barely reach an accuracy of 80%. Additionally, the generalizability across multiple sites of the models has not been investigated. Due to the lack of ASD subtypes identification model, the multi-class classification is proposed in the present study. This study aims to develop automated identification of autism spectrum disorder (ASD) subtypes using convolutional neural networks (CNN) using dynamic FC as its inputs. The rs-fMRI dataset used in this study consists of 144 individuals from 8 independent sites, labeled based on three ASD subtypes, namely autistic disorder (ASD), Asperger’s disorder (APD), and pervasive developmental disorder not otherwise specified (PDD-NOS). The blood-oxygen-level-dependent (BOLD) signals from 116 brain nodes of automated anatomical labeling (AAL) atlas are used, where the top-ranked node is determined based on one-way analysis of variance (ANOVA) of the power spectral density (PSD) values. Based on the statistical analysis of the PSD values of 3-level ASD and normal control (NC), putamen_R is obtained as the top-ranked node and used for the wavelet coherence computation. With good resolution in time and frequency domain, scalograms of wavelet coherence between the top-ranked node and the rest of the nodes are used as dynamic FC feature input to the convolutional neural networks (CNN). The dynamic FC patterns of wavelet coherence scalogram represent phase synchronization between the pairs of BOLD signals. Classification algorithms are developed using CNN and the wavelet coherence scalograms for binary and multi-class identification were trained and tested using cross-validation and leave-one-out techniques. Results of binary classification (ASD vs. NC) and multi-class classification (ASD vs. APD vs. PDD-NOS vs. NC) yielded, respectively, 89.8% accuracy and 82.1% macro-average accuracy, respectively. Findings from this study have illustrated the good potential of wavelet coherence technique in representing dynamic FC between brain nodes and open possibilities for its application in computer aided diagnosis of other neuropsychiatric disorders, such as depression or schizophrenia.

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2. Eow SY, Gan WY, Lim PY, Awang H, Mohd Shariff Z. Parental Feeding Practices and Child-Related Factors are Associated with Overweight and Obesity in Children and Adolescents with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2021.

Atypical eating behaviors displayed by children with autism spectrum disorder (ASD) predispose them to unhealthy weight gain. We determined the factors associated with body weight status among 261 children with ASD (3-18 years) at nine autism intervention centers. Their mothers completed a self-administered questionnaire on sociodemographic background, parenting style, parental feeding practices, parenting stress, sleep habits, eating behaviors, and autism severity. Children with older age, non-full term gestational age, high maternal perceived weight, high maternal concern about child weight, and low pressure to eat were more likely to be overweight and obese. Obesity is a major concern among children with ASD. Healthy weight management programs for parents should incorporate appropriate feeding practices and a healthy perception of body weight.

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3. Jurek L, Baltazar M, Gulati S, Novakovic N, Núñez M, Oakley J, O’Hagan A. Correction to: Response (minimum clinically relevant change) in ASD symptoms after an intervention according to CARS-2: consensus from an expert elicitation procedure. European child & adolescent psychiatry. 2021.

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4. Linnenbank M, Feldmann R, Schulte-Körne G, Beimdiek S, Strittmatter E. Children with Autism Spectrum Disorder of All Ages, Levels of Symptom Severity and General Cognitive Ability Display Low Processing Speed Index Scores Warranting Special Educational Assistance. Journal of autism and developmental disorders. 2021.

The processing speed index (PSI) of the Wechsler intelligence scale for children (WISC-IV) has been found to predict a child’s level of academic functioning. The consistently reported PSI weakness in children with autism spectrum disorder (ASD) therefore warrants special assistance and attempts at compensation for the disadvantages associated with these children’s low PSI. We investigated the association of PSI scores with age, general cognitive ability [as measured by full-scale IQ (FSIQ)], symptom severity and discrepancy between the WISC-IV indices verbal comprehension (VCI) and perceptual reasoning (PRI) in 101 school children with ASD. The PSI weakness in children with ASD was not related to age, FSIQ, VCI-PRI discrepancy or any of the symptom measures. These findings suggest that school children with ASD independent of their age, level of cognitive ability, VCI-PRI profile and most notably independent of their symptom severity should be entitled to special assistance and compensation in educational settings.

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5. Lu M, Wang R, Zou Y, Pang F. Chinese College Students’ Knowledge of Autism Spectrum Disorder (ASD) and Social Distance from Individuals with ASD: The Mediating Role of Negative Stereotypes. Journal of autism and developmental disorders. 2021.

This study investigated whether negative stereotypes are responsible for the effect of ASD knowledge on social distance from individuals with ASD among college students. A sample of 869 neurotypical Chinese college students completed a cross-sectional survey to assess social distance, ASD knowledge, and negative stereotypes. Pearson correlation analysis yielded significant correlations between social distance, ASD knowledge, and negative stereotypes. Multiple mediation analysis showed that negative stereotypes mediated the link between social distance and ASD knowledge. Specifically, greater ASD knowledge predicted reduced social distance through decreased stereotyping related to dangerousness, personal responsibility for the disorder, and discontinuity, but also predicted greater social distance through increased stereotyping related to social inappropriateness. The findings deepen our understanding of the association between ASD knowledge and social distance by revealing the mediating role of negative stereotypes, and provide information that can help improve anti-stigma initiatives in college settings.

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6. Morris E, O’Donovan M, Virani A, Austin J. An ethical analysis of divergent clinical approaches to the application of genetic testing for autism and schizophrenia. Human genetics. 2021.

Genetic testing to identify genetic syndromes and copy number variants (CNVs) via whole genome platforms such as chromosome microarray (CMA) or exome sequencing (ES) is routinely performed clinically, and is considered by a variety of organizations and societies to be a « first-tier » test for individuals with developmental delay (DD), intellectual disability (ID), or autism spectrum disorder (ASD). However, in the context of schizophrenia, though CNVs can have a large effect on risk, genetic testing is not typically a part of routine clinical care, and no clinical practice guidelines recommend testing. This raises the question of whether CNV testing should be similarly performed for individuals with schizophrenia. Here we consider this proposition in light of the history of genetic testing for ID/DD and ASD, and through the application of an ethical analysis designed to enable robust, accountable and justifiable decision-making. Using a systematic framework and application of relevant bioethical principles (beneficence, non-maleficence, autonomy, and justice), our examination highlights that while CNV testing for the indication of ID has considerable benefits, there is currently insufficient evidence to suggest that overall, the potential harms are outweighed by the potential benefits of CNV testing for the sole indications of schizophrenia or ASD. However, although the application of CNV tests for children with ASD or schizophrenia without ID/DD is, strictly speaking, off-label use, there may be clinical utility and benefits substantive enough to outweigh the harms. Research is needed to clarify the harms and benefits of testing in pediatric and adult contexts. Given that genetic counseling has demonstrated benefits for schizophrenia, and has the potential to mitigate many of the potential harms from genetic testing, any decisions to implement genetic testing for schizophrenia should involve high-quality evidence-based genetic counseling.

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7. Sobral da Silva PF, Eickmann SH, Ximenes RAA, Martelli CMT, Brickley EB, M CL, Montarroyos UR, Carvalho M, Rodrigues LC, Araújo TVB, Ventura LO, da Silva Oliveira DM, Ferreira Ramos RC, Miranda-Filho DB, On Behalf Of The Microcephaly Epidemic Research Group M. Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?. Viruses. 2021; 13(8).

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

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8. Svindt V, Surányi B. The comprehension of grammaticalized implicit meanings in SPCD and ASD children: A comparative study. International journal of language & communication disorders. 2021; 56(6): 1147-64.

BACKGROUND: Autism spectrum disorder (ASD) and social pragmatic communication disorder (SPCD) are two neurodevelopmental disorders with many similarities in affected individuals’ impairments in social-communicative and pragmatic development. A central question pertaining to their differentiation concerns whether the distinction is truly qualitative or, instead, quantitative in nature, and indeed, defining the boundary between SPCD and ASD with IQ in the normal range often presents differential-diagnostic difficulties. While deficits in the comprehension of certain linguistically systematic implicit verbal meanings have been targeted by experimental research in ASD, to date they have not been investigated in controlled experiments in SPCD. AIMS: The empirical objectives of our study are twofold. First, it is explored whether the comprehension of a set of highly systematic, grammaticalized implicit meanings is impaired in ASD and SPCD children compared to their typically developing (TD) peers, and whether ASD and SPCD children differ from each other in accessing these verbal meanings. Second, it is investigated whether receptive grammatical competence and first-order ToM abilities are associated with children’s performance in any way and whether there is a difference in this regard between the ASD and the SPCD group. METHODS & PROCEDURES: Our main experiment, using a sentence-picture verification task, tested the comprehension of highly systematic implicit verbal meanings, including grammaticalized implicatures, presuppositions, and entailments. The experiment was complemented with a false-belief (ToM) task and a test of receptive grammar, among other measures. Seventy-one 4-to-9-year-old children participated in the study (ASD: n=19, SPCD: n=13, TD controls: n=39). OUTCOMES & RESULTS: While both children with SPCD and children with ASD performed significantly more poorly than the TD group, only the comprehension profile of the SPCD group differed significantly from that of the TD group. Importantly, while ASDs’ performance exhibited an association with their ToM results, the performance of SPCDs showed a correlation with their receptive grammar skills. By contrast, the performance of TDs correlated with neither. CONCLUSIONS & IMPLICATIONS: These findings reveal potential divergences in the cognitive developmental mechanisms that underlie the semantic-pragmatic difficulties in the two clinical groups, suggesting that the communicative impairments in ASD and in SPCD differ qualitatively, rather than quantitatively. Specific implications for theories of pragmatic impairments in ASD and in SPCD are discussed. WHAT THIS PAPER ADDS: What is already known on the subject Linguistically systematic implicit meanings are understudied both in ASD and in SPCD. Within this domain of verbal meaning, the majority of relevant experimental work on ASD, concentrated on generalized (mostly: scalar) implicatures, has yielded somewhat divergent results, while the comprehension difficulties in SPCD have remained barely charted territory. Linguistically more highly conventionalized implicit verbal meanings have not been experimentally investigated in either neurodevelopmental disorder. What this study adds A primary finding of our study is that although both the SPCD and the ASD group show significant deficit in the comprehension of highly conventional, grammaticalized implicit meanings, SPCD children may diverge more in their comprehension profile from their TD peers than ASD children. Another key result is that the comprehension of grammaticalized implicit meanings is linked with different cognitive functions in ASD and in SPCD. While comprehension performance is associated with ToM in ASD but not in SPCD or in TD, it is correlated with receptive grammar skills in SPCD but not in ASD or in TD. Clinical implications of this study These findings provide potential support for the hypothesis that the difference between ASD and SPCD is qualitative rather than quantitative in nature, thereby casting doubt on the conception that pragmatic limitations in SPCD are to be approached as a less severe form of similar deficits in ASD. Uncovering differences in the underlying cognitive sources and in the comprehension deficits of children with ASD and SPCD are critical for the improvement of the accuracy of SPCD children’s early diagnosis and timely therapeutic intervention.

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9. Xie J, Han Q, Wei Z, Wang Y, Wang S, Chen M. Phenanthrene induces autism-like behavior by promoting oxidative stress and mTOR pathway activation. Toxicology. 2021; 461: 152910.

Autism is thought to be associated with both environmental and genetic factors. Phenanthrene (Phe) makes up a relatively high proportion of the low-ring polycyclic aromatic hydrocarbons. However, the association between exposure to Phe and Autism remain unclear. In this study, the effect and mechanisms of phenanthrene exposure on autistic behavior were investigated. Three-week-old male Kunming mice were exposed to doses of 5, 50, or 500 μg/kg/d Phe for 22 days. Exposure to phenanthrene induced a marked decrease in the activity of the mice in the central area in the open field test, and caused a significant decrease in communication with unfamiliar mice in the three-chambered social test. The hippocampus of the mice exposed to high concentrations of Phe showed pathological changes. Exposure to phenanthrene induced an increase in the levels of ROS and a decrease in levels of glutathione, and caused a significant decrease in the expression of Shank3 and Beclin1. This also led to an increase in the phosphorylation levels of Akt and mTOR. However, administering Rapamycin or vitamin E, inhibited the oxidative stress and activation of the mTOR pathway induced by Phe exposure, effectively alleviating the above-mentioned autistic-like anxious social behaviors. These results indicate that exposure to phenanthrene will lead to autism-like behavior. The underlying mechanism involves oxidative stress and the mTOR pathway.

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