1. Adams JR, Salem AC, MacFarlane H, Ingham R, Bedrick SD, Fombonne E, Dolata JK, Hill AP, van Santen J. A Pseudo-Value Approach to Analyze the Semantic Similarity of the Speech of Children With and Without Autism Spectrum Disorder. Frontiers in psychology. 2021; 12: 668344.

Conversational impairments are well known among people with autism spectrum disorder (ASD), but their measurement requires time-consuming manual annotation of language samples. Natural language processing (NLP) has shown promise in identifying semantic difficulties when compared to clinician-annotated reference transcripts. Our goal was to develop a novel measure of lexico-semantic similarity – based on recent work in natural language processing (NLP) and recent applications of pseudo-value analysis – which could be applied to transcripts of children’s conversational language, without recourse to some ground-truth reference document. We hypothesized that: (a) semantic coherence, as measured by this method, would discriminate between children with and without ASD and (b) more variability would be found in the group with ASD. We used data from 70 4- to 8-year-old males with ASD (N = 38) or typically developing (TD; N = 32) enrolled in a language study. Participants were administered a battery of standardized diagnostic tests, including the Autism Diagnostic Observation Schedule (ADOS). ADOS was recorded and transcribed, and we analyzed children’s language output during the conversation/interview ADOS tasks. Transcripts were converted to vectors via a word2vec model trained on the Google News Corpus. Pairwise similarity across all subjects and a sample grand mean were calculated. Using a leave-one-out algorithm, a pseudo-value, detailed below, representing each subject’s contribution to the grand mean was generated. Means of pseudo-values were compared between the two groups. Analyses were co-varied for nonverbal IQ, mean length of utterance, and number of distinct word roots (NDR). Statistically significant differences were observed in means of pseudo-values between TD and ASD groups (p = 0.007). TD subjects had higher pseudo-value scores suggesting that similarity scores of TD subjects were more similar to the overall group mean. Variance of pseudo-values was greater in the ASD group. Nonverbal IQ, mean length of utterance, or NDR did not account for between group differences. The findings suggest that our pseudo-value-based method can be effectively used to identify specific semantic difficulties that characterize children with ASD without requiring a reference transcript.

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2. Butera C, Ring P, Sideris J, Jayashankar A, Kilroy E, Harrison L, Cermak S, Aziz-Zadeh L. Impact of Sensory Processing on School Performance Outcomes in High Functioning Individuals with Autism Spectrum Disorder. Mind, brain and education : the official journal of the International Mind, Brain, and Education Society. 2020; 14(3): 243-54.

Difficulty processing sensory information may impede progress in school for students with autism spectrum disorder (ASD). We explore the relationship between sensory processing and school performance in 26 high-functioning youths with ASD and 26 controls (age 8-14) using measures of sensory, social, cognitive, and academic functioning. In the ASD group, bivariate Pearson correlations indicated a significant positive relationship between intelligence quotient (IQ) and the School Competence Scale (SCS) of the Child Behavior Checklist (CBCL), and a significant negative relationship between Dunn’s Sensory Processing Framework and SCS scores. Final hierarchical multiple linear regression model accounting for SCS scores in ASD included IQ, ADHD symptoms, and sensory features. An interaction between increased sensory sensitivity with reduced sensory avoidance behaviors explained the greatest amount of variance in SCS, meaning school performance is lowest for children with greater hypersensitivity and fewer avoidance behaviors. Results indicate a strong impact of sensory processing on school performance in ASD.

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3. da Silva PR, do Nascimento Gonzaga TKS, Maia RE, da Silva BA. Ionic Channels as Potential Targets for the Treatment of Autism Spectrum Disorder: A Review. Current neuropharmacology. 2021.

Autism spectrum disorder (ASD) is a neurological condition that directly affects brain functions and can culminate in delayed intellectual development, problems in verbal communication, difficulties in social interaction and stereotyped behaviors. Its etiology reveals a genetic basis which can be strongly influenced by socio-environmental factors. Ion channels controlled by ligand voltage- activated calcium, sodium, and potassium channels may play important roles in modulating sensory and cognitive responses, and their dysfunctions may be closely associated with neurodevelopmental disorders such as ASD. This is due to ionic flow, which is of paramount importance to maintaining physiological conditions in the central nervous system, and triggers action potentials, gene expression, and cell signaling. However, since ASD is a multifactorial disease, treatment is directed only to secondary symptoms. Therefore, this research aims to gather evidence concerning the principal pathophysiological mechanisms involving ion channels, in order to recognize their importance as therapeutic targets for treatment of central and secondary ASD symptoms.

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4. D’Arcy E, Wallace K, Chamberlain A, Evans K, Milbourn B, Bölte S, Whitehouse AJ, Girdler S. Content validation of common measures of functioning for young children against the International Classification of Functioning, Disability and Health and Code and Core Sets relevant to neurodevelopmental conditions. Autism : the international journal of research and practice. 2022; 26(4): 928-39.

Young children who have developmental delay, autism, or other neurodevelopmental conditions can have difficulties doing things in different areas of their life. What they can and cannot do is called their level of functioning. There are lots of assessment measures that aim to assess functioning. But, we are not sure if these measures assess all the things we need to know about these children’s functioning. Other research has identified lists of items (codes) that need to be assessed to understand functioning for young children with different neurodevelopmental conditions fully. These lists include body functions (the things a child’s body or brain can do), activities and participation (the activities and tasks a child does) and environmental factors (parts of the environment that can influence functioning). In this study, we looked at the items from these lists assessed by different functioning measures to see how they compared to what should be assessed. The measures that we looked at covered 21%-57% of all the codes and 19%-63% of the codes for lists specific to different conditions. Most of the measures focused on activity and participation codes, and they rarely assessed environmental factors. Knowing which codes and how much of the lists the measures assess can help researchers, clinicians and policymakers to choose measures that are more appropriate for young children with neurodevelopmental conditions.

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5. Fennell LCP, Johnson SA. Examination of professional biases about autism: how can we do better?. The Clinical neuropsychologist. 2021: 1-22.

This paper lends a critical eye to six common assumptions/biases about autism that may influence neuropsychologists in their clinical work. These biases are based on research as well as the historical roots of the study of autism. Our goal is to encourage curiosity and reflection on these biases in order to improve neuropsychological service delivery for people on the autism spectrum. Methods: We argue that psychologists should strive to understand the function of behaviours observed with autism in order to offer helpful supports. We explore the assertions that autism is not a dichotomous or linear construct and that the use of high and low functioning descriptors are not useful nor appreciated by the autism community. We discuss the widely held beliefs that individuals on the autism spectrum lack theory of mind, empathy and social motivation. Importantly, people on the autism spectrum are telling us that the dialogue about them around theory of mind and empathy is a human rights issue. Finally, we discuss the role of standardized testing. Conclusions: Through an exploration of research literature, the writings of scholars and advocates on the autism spectrum, and personal, clinical and research experience we encourage our profession to take a leadership role in examining biases and changing the clinical and research landscape so that it better reflects respectful discourse for individuals on the autism spectrum. This is critical to reduce the stigma that continues to be associated with autism and has a negative affect on mental health and quality of life.

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6. Jannati A, Ryan MA, Kaye HL, Tsuboyama M, Rotenberg A. Biomarkers Obtained by Transcranial Magnetic Stimulation in Neurodevelopmental Disorders. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2022; 39(2): 135-48.

Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation that is based on the principle of electromagnetic induction where small intracranial electric currents are generated by a powerful fluctuating magnetic field. Over the past three decades, TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disorders in adults. However, the use of TMS in children has been more limited. We provide a brief introduction to the TMS technique; common TMS protocols including single-pulse TMS, paired-pulse TMS, paired associative stimulation, and repetitive TMS; and relevant TMS-derived neurophysiological measurements including resting and active motor threshold, cortical silent period, paired-pulse TMS measures of intracortical inhibition and facilitation, and plasticity metrics after repetitive TMS. We then discuss the biomarker applications of TMS in a few representative neurodevelopmental disorders including autism spectrum disorder, fragile X syndrome, attention-deficit hyperactivity disorder, Tourette syndrome, and developmental stuttering.

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7. Kennedy DP. Illuminating Autism Spectrum Disorder With Eye Tracking. Biological psychiatry Cognitive neuroscience and neuroimaging. 2021; 6(8): 765-6.

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8. Khundrakpam B, Tuerk C, Booij L. Understanding Heterogeneity in Autism Spectrum Disorder: A Methodological Shift in Neuroimaging Research From Investigating Group Differences to Individual Differences. Biological psychiatry Cognitive neuroscience and neuroimaging. 2021; 6(8): 762-4.

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9. Kosillo P, Bateup HS. Dopaminergic Dysregulation in Syndromic Autism Spectrum Disorders: Insights From Genetic Mouse Models. Frontiers in neural circuits. 2021; 15: 700968.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by altered social interaction and communication, and repetitive, restricted, inflexible behaviors. Approximately 1.5-2% of the general population meet the diagnostic criteria for ASD and several brain regions including the cortex, amygdala, cerebellum and basal ganglia have been implicated in ASD pathophysiology. The midbrain dopamine system is an important modulator of cellular and synaptic function in multiple ASD-implicated brain regions via anatomically and functionally distinct dopaminergic projections. The dopamine hypothesis of ASD postulates that dysregulation of dopaminergic projection pathways could contribute to the behavioral manifestations of ASD, including altered reward value of social stimuli, changes in sensorimotor processing, and motor stereotypies. In this review, we examine the support for the idea that cell-autonomous changes in dopaminergic function are a core component of ASD pathophysiology. We discuss the human literature supporting the involvement of altered dopamine signaling in ASD including genetic, brain imaging and pharmacologic studies. We then focus on genetic mouse models of syndromic neurodevelopmental disorders in which single gene mutations lead to increased risk for ASD. We highlight studies that have directly examined dopamine neuron number, morphology, physiology, or output in these models. Overall, we find considerable support for the idea that the dopamine system may be dysregulated in syndromic ASDs; however, there does not appear to be a consistent signature and some models show increased dopaminergic function, while others have deficient dopamine signaling. We conclude that dopamine dysregulation is common in syndromic forms of ASD but that the specific changes may be unique to each genetic disorder and may not account for the full spectrum of ASD-related manifestations.

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10. Leader G, Dooley E, Whelan S, Gilroy SP, Chen JL, Farren Barton A, Coyne R, Mannion A. Attention-Deficit/Hyperactivity Disorder Symptoms, Gastrointestinal Symptoms, Sleep Problems, Challenging Behavior, Adaptive Behavior, and Quality of Life in Children and Adolescents with Autism Spectrum Disorder. Developmental neurorehabilitation. 2022; 25(4): 217-28.

This study investigated the relationship between sleep, gastrointestinal symptoms, challenging behavior, adaptive behavior, and quality of life between children and adolescents with autism spectrum disorder (ASD), with and without attention-deficit/hyperactivity disorder (AD/HD) symptoms. Parents of 118 children and adolescents with ASD completed the Conners Early Childhood Rating Scale-Parent Short Form or the Conners 3-Parent Short Form, Children’s Sleep Habits Questionnaire, Gastrointestinal Symptom Inventory, Behavior Problems Inventory-Short Form, Pediatric Quality of Life Inventory and the Vineland Adaptive Behavior Scales, Second Edition. The ASD group and the ASD with AD/HD groups differed significantly in sleep problems, gastrointestinal symptoms, and quality of life. Regressions indicated that AD/HD symptoms accounted for a small proportion of the variance for the differences in sleep problems and quality of life. AD/HD symptoms contribute to the complex needs of individuals with ASD. Research is necessary to investigate how these symptoms exacerbate comorbidities.

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11. Lecciso F, Levante A, Fabio RA, Caprì T, Leo M, Carcagnì P, Distante C, Mazzeo PL, Spagnolo P, Petrocchi S. Emotional Expression in Children With ASD: A Pre-Study on a Two-Group Pre-Post-Test Design Comparing Robot-Based and Computer-Based Training. Frontiers in psychology. 2021; 12: 678052.

Several studies have found a delay in the development of facial emotion recognition and expression in children with an autism spectrum condition (ASC). Several interventions have been designed to help children to fill this gap. Most of them adopt technological devices (i.e., robots, computers, and avatars) as social mediators and reported evidence of improvement. Few interventions have aimed at promoting emotion recognition and expression abilities and, among these, most have focused on emotion recognition. Moreover, a crucial point is the generalization of the ability acquired during treatment to naturalistic interactions. This study aimed to evaluate the effectiveness of two technological-based interventions focused on the expression of basic emotions comparing a robot-based type of training with a « hybrid » computer-based one. Furthermore, we explored the engagement of the hybrid technological device introduced in the study as an intermediate step to facilitate the generalization of the acquired competencies in naturalistic settings. A two-group pre-post-test design was applied to a sample of 12 children (M = 9.33; ds = 2.19) with autism. The children were included in one of the two groups: group 1 received a robot-based type of training (n = 6); and group 2 received a computer-based type of training (n = 6). Pre- and post-intervention evaluations (i.e., time) of facial expression and production of four basic emotions (happiness, sadness, fear, and anger) were performed. Non-parametric ANOVAs found significant time effects between pre- and post-interventions on the ability to recognize sadness [t ((1)) = 7.35, p = 0.006; pre: M (ds) = 4.58 (0.51); post: M (ds) = 5], and to express happiness [t ((1)) = 5.72, p = 0.016; pre: M (ds) = 3.25 (1.81); post: M (ds) = 4.25 (1.76)], and sadness [t ((1)) = 10.89, p < 0; pre: M (ds) = 1.5 (1.32); post: M (ds) = 3.42 (1.78)]. The group(*)time interactions were significant for fear [t ((1)) = 1.019, p = 0.03] and anger expression [t ((1)) = 1.039, p = 0.03]. However, Mann-Whitney comparisons did not show significant differences between robot-based and computer-based training. Finally, no difference was found in the levels of engagement comparing the two groups in terms of the number of voice prompts given during interventions. Albeit the results are preliminary and should be interpreted with caution, this study suggests that two types of technology-based training, one mediated via a humanoid robot and the other via a pre-settled video of a peer, perform similarly in promoting facial recognition and expression of basic emotions in children with an ASC. The findings represent the first step to generalize the abilities acquired in a laboratory-trained situation to naturalistic interactions.

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12. Lépine J, Gagnon K, Prud’homme J, Vinay MC, Doussau A, Fourdain S, Provost S, Belval V, Bernard C, Gallagher A, Poirier N, Simard MN. Utility of the Ages and Stages Questionnaires 3rd Edition for Developmental Screening in Children with Surgically Repaired Congenital Heart Disease. Developmental neurorehabilitation. 2022; 25(2): 125-32.

Aim: This study sought to evaluate the accuracy of the Ages and Stages Questionnaires 3rd Edition (ASQ-3) in identifying developmental delay (DD) in children with congenital heart disease (CHD) born at term who underwent surgical repair.Methods: Participants had to complete ASQ-3 and Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III) at 12 and 24 months. A child was considered at risk of DD for a ASQ-3 domain when he scored below the cutoff (≤-1SD or ≤-2SD). A child had a DD in a BSID-III domain when the score was ≤-1SD. The validity for each ASQ-3 domain and for overall ASQ-3 was measured.Results: At 12 months (n = 64), overall ASQ-3 (≤-2SD) sensitivity was 88%, specificity 74%. At 24 months (n = 82), overall ASQ-3 (≤-2SD) sensitivity was 74%, specificity 88%.Conclusion: The results support the utility of the ASQ-3 for screening the overall risk of DD in children with CHD.

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13. Lois Mosquera M, Mandy W, Pavlopoulou G, Dimitriou D. Autistic adults’ personal experiences of navigating a social world prior to and during Covid-19 lockdown in Spain. Research in developmental disabilities. 2021; 117: 104057.

BACKGROUND: The SARS-CoV-2 coronavirus pandemic brought significant movement restrictions and national lockdowns. These drastic changes impacted routines, social life and support networks for the autistic community. AIMS: This study investigated the lived experiences of autistic adults with social expectations before and during the first Covid-19 lockdown in Spain. METHODS: A qualitative Reflexive Thematic Analysis was applied to 10 Photo Elicitation Interviews using images provided by five autistic adults. Interviews were conducted at two time points, before the pandemic and during the first lockdown. FINDINGS: Three themes before the pandemic were identified: (1) everyday interactions, (2) finding sense of belonging, and (3) fractured wellbeing, which revealed the participants’ eagerness to fit in socially whilst experiencing rejection, weakening their mental health. During the first Covid-19 lockdown, two master themes were identified: (1) daily, positive experiences, and (2) surfacing failures, which emphasised an increased lived stigma as well as an ineffective autism support network, contributing to a heightened anxiety. CONCLUSIONS: The current study provides further support to the recent findings highlighting lack of appropriate mental health support for the autistic communities during the pandemic, across the world. Future research should aim to provide more data on the experiences and needs of autistic communities when sudden societal changes are imposed.

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14. Malow BA, Galion A, Lu F, Kennedy N, Lawrence CE, Tassone A, O’Neal L, Wilson TM, Parker RA, Harris PA, Neumeyer AM. A REDCap-based model for online interventional research: Parent sleep education in autism. Journal of clinical and translational science. 2021; 5(1): e138.

INTRODUCTION: The use of online platforms for pediatric healthcare research is timely, given the current pandemic. These platforms facilitate trial efficiency integration including electronic consent, randomization, collection of patient/family survey data, delivery of an intervention, and basic data analysis. METHODS: We created an online digital platform for a multicenter study that delivered an intervention for sleep disorders to parents of children with autism spectrum disorder (ASD). An advisory parent group provided input. Participants were randomized to receive either a sleep education pamphlet only or the sleep education pamphlet plus three quick-tips sheets and two videos that reinforced the material in the pamphlet (multimedia materials). Three measures – Family Inventory of Sleep Habits (FISH), Children’s Sleep Habits Questionnaire modified for ASD (CSHQ-ASD), and Parenting Sense of Competence (PSOC) – were completed before and after 12 weeks of sleep education. RESULTS: Enrollment exceeded recruitment goals. Trial efficiency was improved, especially in data entry and automatic notification of participants related to survey completion. Most families commented favorably on the study. While study measures did not improve with treatment in either group (pamphlet or multimedia materials), parents reporting an improvement of ≥3 points in the FISH score showed a significantly improved change in the total CSHQ (P = 0.038). CONCLUSION: Our study demonstrates the feasibility of using online research delivery platforms to support studies in ASD, and more broadly, pediatric clinical and translational research. Online platforms may increase participant inclusion in enrollment and increase convenience and safety for participants and study personnel.

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15. Northrup JB, Patterson MT, Mazefsky CA. Predictors of Severity and Change in Emotion Dysregulation among Children and Adolescents with ASD. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53. 2021; 50(6): 708-29.

OBJECTIVE: Emotion dysregulation problems are prevalent and disruptive for many with autism spectrum disorder (ASD). This study compared severity and perceived change in emotion dysregulation in youth with and without ASD and probed correlates of emotion dysregulation (including possible two-way interactions) among youth with ASD. METHOD: Participants were drawn from two large online samples (mean age = 12; range: 6-17) with (N = 1323) and without (N = 921) ASD. The study used the Emotion Dysregulation Inventory (EDI), a parent-report measure designed for youth with ASD. The EDI asks parents about current severity and perceived change (i.e. how current severity compares to lifetime severity) in emotion dysregulation, and includes two factors: Reactivity (rapidly escalating, intense negative affect) and Dysphoria (poorly upregulated positive affect, general unease). RESULTS: Results indicated that youth with ASD had greater Reactivity severity and also greater positive change in Reactivity than non-ASD peers. Furthermore, differences between youth with and without ASD in the relationship between Reactivity and Dysphoria suggest a distinct profile of emotion dysregulation in ASD. Within the ASD sample, age and severity of stereotyped behavior predicted Reactivity and Dysphoria severity and Reactivity change. Female gender, lower parent education, and fluent verbal ability were additional predictors of increased Reactivity severity, while intellectual disability predicted lower Dysphoria severity. CONCLUSIONS: This study provides new insight into predictors of emotion dysregulation in youth with ASD and represents a first step toward identifying which children with ASD may be most vulnerable to severe emotion dysregulation problems.

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16. PÅhlman M, Gillberg C, Himmelmann K. Neuroimaging findings in children with cerebral palsy with autism and/or attention-deficit/hyperactivity disorder: a population-based study. Developmental medicine and child neurology. 2022; 64(1): 63-9.

AIM: To compare neuroimaging patterns according to the Magnetic Resonance Imaging Classification System (MRICS) in children with cerebral palsy (CP) with and without autism and/or attention-deficit/hyperactivity disorder (ADHD). METHOD: This population-based study assessed 184 children (97 males, 87 females) with CP born from 1999 to 2006 from the CP register of western Sweden, who had completed comprehensive screening and clinical assessment for neuropsychiatric disorders and undergone neuroimaging. RESULTS: Autism (total prevalence 30%) and ADHD (31%) were common in all neuroimaging patterns, including normal. Autism and ADHD were not more prevalent in children with bilateral than unilateral lesions, contrary to other associated impairments. Children with predominant white matter injury, related to insults in the late second or early third trimester, had the highest prevalence of autism (40%). Children who had sustained a middle cerebral artery infarction had the highest prevalence of ADHD (62%). INTERPRETATION: Although autism and ADHD are common regardless of neuroimaging patterns, timing and localization of insult appear to be of importance for the occurrence of autism and ADHD in children with CP. Neuroimaging may be of prognostic value for these associated impairments. Further in-depth neuroimaging studies may lead to a better understanding of the association between CP and neuropsychiatric disorders.

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17. Robert T, Dock-Bregeon AC, Colas P. Functional characterization of CDK10 and cyclin M truncated variants causing severe developmental disorders. Molecular genetics & genomic medicine. 2021; 9(10): e1782.

BACKGROUND: CDK10 is a poorly known cyclin M (CycM)-dependent kinase. Loss-of-function mutations in the genes encoding CycM or CDK10 cause, respectively, STAR or Al Kaissi syndromes, which present a constellation of malformations and dysfunctions. Most reported mutations abolish gene expression, but two mutations found in 3′ exons could allow the expression of CDK10 and CycM truncated variants. METHODS: We built a structural model that predicted a preserved ability of both variants to form a CDK10/CycM heterodimer. Hence, we functionally characterized these two truncated variants by determining their capacity to heterodimerize and form an active protein kinase when expressed in insect cells, by examining their two-hybrid interaction profiles when expressed in yeast, and by observing their expression level and stability when expressed in human cells. RESULTS: Both truncated variants retain their ability to form a CDK10/CycM heterodimer. While the CycM variant partially activates CDK10 activity in vitro, the CDK10 variant remains surprisingly inactive. Expression in human cells revealed that the CDK10 and CycM variants are strongly and partially degraded by the proteasome, respectively. CONCLUSION: Our results point to a total loss of CDK10/CycM activity in the Al Kaissi patient and a partial loss in the STAR patients.

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18. Sharma AR, Batra G, Saini L, Sharma S, Mishra A, Singla R, Singh A, Singh RS, Jain A, Bansal S, Modi M, Medhi B. Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure. CNS & neurological disorders drug targets. 2022; 21(5): 399-408.

Autism spectrum disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi- targeting agent and affects 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by other important factors like vitamin A deficiency. Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc., are also altered in ASD and involved in brain development, central nervous system, and enteric nervous system. These genes affect neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance lead to improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.

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19. Shen L, Li P, Zheng T, Luo M, Zhang S, Huang Y, Hu Y, Li H. Comparative analysis of the autism‑related variants between different autistic children in a family pedigree. Molecular medicine reports. 2021; 24(4).

The present study aimed to provide evidence for the genetic heterogeneity of familial autism spectrum disorder (ASD), which might help to improve our understanding of the complex polygenic basis of this disease. Whole‑exome sequencing (WES) was performed on two autistic children in a family pedigree, and reasonable conditions were set for preliminarily screening variant annotations. Sanger sequencing was used to verify the preliminarily screened variants and to determine the possible sources. In addition, autism‑related genes were screened according to autism databases, and their variants were compared between two autistic children. The results showed that there were 21 genes respectively for autistic children Ⅳ2 and Ⅳ4, preliminarily screened from all variants based on the harmfulness (high) and quality (high or medium) of the variants, as well as the association between mutant genes and autism in human gene mutation database. Furthermore, candidate autism‑related genes were screened according to the evidence score of >4 in the Autism KnowledgeBase (AutismKB) database or ≥3 in the AutDB database. A total of 11 and 10 candidate autism‑related genes were identified in the autistic children Ⅳ2 and Ⅳ4, respectively. Candidate genes with an evidence score of >16 in AutismKB were credible autism‑related genes, which included LAMC3, JMJD1C and CACNA1H in child Ⅳ2, as well as SCN1A, SETD5, CHD7 and KCNMA1 in child Ⅳ4. Other than the c.G1499A mutation of SCN1A, which is known to be associated with Dravet syndrome, the specific missense variant loci of other six highly credible putative autism‑related genes were reported for the first time, to the best of the authors’ knowledge, in the present study. These credible autism‑related variants were inherited not only from immediate family members but also from extended family members. In summary, the present study established a reasonable and feasible method for screening credible autism‑related genes from WES results, which by be worth extending into clinical practice. The different credible autism‑related genes between the two autistic children indicated a complex polygenic architecture of ASD, which may assist in the early diagnosis of this disease.

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20. Thorsteinsdottir S, Njardvik U, Bjarnason R, Haraldsson H, Olafsdottir AS. Taste education – A food-based intervention in a school setting, focusing on children with and without neurodevelopmental disorders and their families. A randomized controlled trial. Appetite. 2021; 167: 105623.

Children with neurodevelopmental disorders (ND) such as Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactive Disorder (ADHD) have high levels of fussy eating. However, no school-based food interventions exist for children with ASD and ADHD. To investigate the effect of Taste Education, 81 children with ND (n = 33), and without (n = 48), aged 8-12 years, and their parents, participated in a 7-week food intervention. Children were matched on age, ND, and sex, and randomized into Immediate-intervention and Delayed-intervention groups. Parents completed the Children’s Eating Behaviour Questionnaire (CEBQ), and a food-variety questionnaire. After adjusting for baseline measures, repeated-measures analysis-of-variance with time-points, and condition as factors (Immediate intervention and Delayed intervention) were used to examine changes in CEBQ-scores, with a robust linear mixed-model fitted. Changes in percentage of accepted foods were tested using a logistic-regression model adjusting for baseline acceptance. Results showed superior results for Intervention compared to waiting, on Food fussiness, but not Enjoyment of food, with stable effects through six-months follow-up. There were non-significant differences between children with and without ND. Results also showed increased odds of accepting vegetables by a factor of 1.6 (95% Confidence Interval [CI]: 1.33-1.93, p < .001); nuts and seeds by a factor of 1.4 (95% CI: 1.27-1.6, p < .001), but no significant association for fruit (OR 1.12, 95% CI: 0.92-1.34, p = .244). Trends were similar for children regardless of ND-status. The Taste Education program, shows promise, as a simple, non-invasive way to decrease fussy eating and increase food variety in the long-term.

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21. Yang S, Wu L, Liao H, Lu X, Zhang X, Kuang X, Yang L. Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation. Neurogenetics. 2021; 22(4): 323-32.

Mutations in CSNK2B lead to Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), a rare neurodevelopmental disorder. Only 14 cases of POBINDS have been reported worldwide. The main manifestations are seizures, often tonic-clonic, with or without intellectual disability, growth retardation, and developmental language retardation. We conducted a comprehensive phenotypic mining and trio-whole exome sequencing on six children with POBINDS for gene diagnosis and analyzed the different variants using bioinformatics analysis software and related experiments. This paper reviews previous literature and discusses two common missense variants that lead to structural changes. Among the six patients, four, one, and one had tonic-clonic, myoclonic, and febrile seizures, respectively. Language development disorder, motor development disorder, and developmental delay/intellectual disability (DD/ID) are the main clinical features. All children had de novo mutations in CSNK2B, including three missense variants (c.410G > T/p.(Cys137Phe), c.494A > G/p.(His165Arg), and c.3G > A/p.(Met1Ile)), two splice variants (c.292-2A > T, c.558-3 T > G), and one frameshift variant (c.499delC/p.(Leu167Serfs*60)). Three missense variants were predicted to be harmful by various software programs, and two splicing variants were found to produce new exonic splicing enhancers by the minigene assay. Western blot analysis showed that the frameshift variant resulted in decreased protein expression. According to a literature review, c.3G > A/p.(Met1Ile), c.292-2A > T, c.558-3 T > G, and c.499delC/p.(Leu167Serfs*60) are novel variants of CSNK2B. The decrease or loss of protein function caused by CSNK2B mutations may be a pathogenic factor in this cohort. The severity of the POBINDS phenotype differs, and refractory epilepsy may be accompanied by a more serious DD/ID, language disorder, and motor retardation. At present, there is no specific treatment, and antiepileptic therapy usually requires the combination of two or more anti-epileptic drugs.

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