1. Bolognesi E, Guerini FR, Sotgiu S, Chiappedi M, Carta A, Mensi MM, Agliardi C, Zanzottera M, Clerici M. GC1f Vitamin D Binding Protein Isoform as a Marker of Severity in Autism Spectrum Disorders. Nutrients. 2022; 14(23).

Autism spectrum disorders (ASD) are characterized by a wide spectrum of clinical, behavioral, and cognitive manifestations. It is, therefore, crucial to investigate possible biomarkers associated with specific ASD phenotypes. Ample literature suggests a possible role for vitamin D (VD) in influencing ASD clinical phenotypes. We analyzed three vitamin D binding protein gene (DBP) functional polymorphisms (rs2282679, rs7041, and rs4588), which are involved in the modulation of vitamin D serum concentration in 309 ASD children and 831 healthy controls. Frequency comparisons of single nucleotide polymorphisms (SNPs) alleles, genotypes, and GC isoforms (GC1f, G1s, and GC2)-generated by the combination of rs7041 and rs4588 alleles-were correlated with ASD diagnostic, behavioral, and functioning scales. The GC1f isoform was significantly more frequent in ASD compared with controls (18.6% vs. 14.5% pc = 0.02). Significantly higher scores for item 15 of the Childhood Autism Rating Scale (CARS) and lower ones for the Children’s Global Assessment Scale (CGAS) functioning scales were seen in ASD carrying the GC1f isoform. In GC phenotype analysis, a gradient of severity for overall CARS scores and CARS item 15 was observed, with scores decreasing according to the presence of GC1f-GC1f > GC1f-GC1s > GC1s-GC1s > GC1f-GC2 > GC2-GC2 isoforms. Similarly, lower CGAS scores were seen in carriers of the GC1f-GC1f isoform, whereas higher scores were present in those carrying GC2-GC2 (p = 0.028). This is the first study to evaluate possible relationships between GC variants and the different aspects of ASD in Italian ASD children. Results, although needing to be validated in ampler cohorts, suggest that the GC1f isoform could be a marker of severity in ASD that may be useful in establishing the intensity of therapeutic and rehabilitative protocols.

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2. Gao YQ, Xu LB, Zhang YY, He LL, Shu ZH, Pan XC. Exploring the nursing effect of application Albizia bark on autism in children based on network pharmacology and molecular docking. European review for medical and pharmacological sciences. 2022; 26(22): 8539-50.

OBJECTIVE: Autism is a disorder that manifests itself in early childhood. Early diagnosis of autism may not only help the affected children themselves, but also affect family well-being and social stability. The natural drug Albizia bark has been reported to have some effect in the prevention and treatment of autism in children. Therefore, we used network pharmacology and molecular docking to explore the possible mechanism. MATERIALS AND METHODS: TCMID and BATMAN-TCM was used to retrieve the chemical constituents of Albizia bark, and then obtained the relevant targets about autism by TTD, Gene Cards and OMIM. The resulting ingredients and targets were predicted, then a protein interaction network was constructed, and finally bioinformatics analysis was performed. Finally, molecular docking was used to verify the effective ingredients and targets obtained from the screening. RESULTS: Leucaena saponin B, luteolin, 3′, 4′, 7-trihydroxyflavone, which may be the key compounds for the treatment of autism. BP mainly involving signal transduction, G protein coupled receptor signal pathway, protein phosphorylation. CC, mainly involving plasma membrane, integral component of plasma membrane, MF, including protein binding, adenosine triphosphate binding, protein kinase activity. Molecular docking showed that AKT1, HRAS, PIK3CA, PIK3R1 and SRC, five potential targets, had good binding ability to Leucaena saponin B. CONCLUSIONS: The natural drug Albizia bark exerts pharmacological effects in a multi-component, multi-target and multi-channel manner, including neural regulation, inflammatory response and immune regulation.

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3. Guner UU, İrem B. The Relationship Between Nutrition-Physical Activity Behaviors of Autistic Children with Their Families and Children’s Obesity Levels During Covid Pandemic. Journal of autism and developmental disorders. 2022: 1-9.

The family has a key role in the obesity management of children with autism. This study examines the relationship between the nutrition-physical activity behaviors of autistic children with their families and children’s obesity levels during covid-19 pandemic. The descriptive and cross-sectional study involved 80 parents of autistic children. A positive correlation was found between children’s mean BMI values before and during the pandemic(p = 0.000). Family Nutrition and Physical Activity Scale(FNPAS) and Brief Autism Mealtime Behavior Inventory(BAMBI) score were 55.18 ± 7.86 and 31.76 ± 8.79, respectively. In addition, it was found that 32.5% of the children ate more than before the pandemic, 50.0% engaged in less physical activity, and 16.3% didn’t do any physical activity. The study results suggesting the risk of obesity.

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4. Hausman NL, Falligant JM, Bednar MK, Carver AN, Connaughton K. Behavioral Treatment of Sleep Problems using Wake-Time Fading with Individuals with Autism: A Brief Report. Developmental neurorehabilitation. 2022: 1-4.

Difficulties with sleep, such as delayed onset, night waking, and early waking, are pervasive among individuals with developmental disabilities and autism. Interventions that seek to improve sleep outcomes are particularly useful when these individuals have experienced extended hospitalizations where low activity levels and decreased exposure to light-dark cycles maintain or increase disturbance in sleep patterns. The current study examines the effects of wake-time phase advances on the sleep patterns of a 16-year-old male and 17-year-old female, both of whom presented with significant sleep disturbance, autism, developmental delays, and severe problem behavior in a hospital-based setting. For both individuals, clinically significant increases in appropriate sleep and decreases in latency to sleep were observed throughout the course of their admission as a result of wake-time phase advances. Together, these results replicate and extend limited research in this area by using behavioral interventions to decrease disrupted sleep in inpatient contexts.

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5. Hedley D, Hedley DF, Walkowiak E, Bury SM, Spoor JR, Shiell A. Cost-benefit analysis of a non-government organization and Australian government collaborative supported employment program for autistic people. Autism : the international journal of research and practice. 2022: 13623613221138643.

Relative to the size of the population, there are fewer autistic people than non-autistic people in the workforce. Employment programs that provide extra support to autistic people may help them to gain and keep jobs that are suited to their skills and expertise. In this study, we reviewed the DXC Dandelion Program. This is a supported autism employment program run in partnership with the Australian Government. The program provided jobs to autistic people who worked in information and communications technology roles, such as software testing and cyber security. In this study, we examined some of the benefits of the program for the autistic people who participated in it. We also examined the benefits of the program to the government. We found that there are many savings to government when autistic people are employed in jobs that are matched to their skills and abilities, compared to being unemployed or working in jobs that are below their level of education, training, or skills.

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6. Hsu JW, Chen LC, Huang KL, Tsai SJ, Bai YM, Su TP, Chen TJ, Chen MH. The influence of sex on major psychiatric comorbidities and parental psychiatric disorders in 22,698 children and adolescents with ICD-9-CM-based autism spectrum disorder. European archives of psychiatry and clinical neuroscience. 2022.

It remains unclear how major psychiatric comorbidities and parental psychiatric disorders differ in males and females with autism spectrum disorder (ASD). Between 2001 and 2011, 17,627 children and 5071 adolescents with ASD (ICD-9-CM code: 299) were identified from Taiwan’s National Health Insurance Research Database and assessed for major psychiatric comorbidities and parental psychiatric disorders. Compared with females with ASD, males with ASD were more likely to be diagnosed as having attention deficit hyperactivity disorder (relative risk [RR], 95% confidence interval [CI] 1.63, 1.51-1.75) and disruptive behavior disorder (1.38, 1.17-1.62) and less likely to be diagnosed as having schizophrenia (0.45, 0.36-0.56), bipolar disorder (0.58, 0.45-0.74), or intellectual disability (0.53, 0.49-0.58). Furthermore, compared with women, having a parental history of schizophrenia (RR, 95% CI 0.66, 0.49-0.89) or intellectual disability (0.34, 0.19-0.61) was less associated with ASD among men. However, the difference in ASD diagnosis between ICD-9-CM and ICD-10/11-CM systems may reflect the different, but surely overlapping, entity of ASD, which may limit the generalization of our results. Additional studies should be performed.

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7. Kuhlthau KA, Traeger L, Luberto CM, Perez GK, Goshe BM, Fell L, Iannuzzi D, Park ER. Resiliency Intervention for Siblings of Children with ASD: A Randomized Pilot Trial. Academic pediatrics. 2022.

BACKGROUND /OBJECTIVES: Neurotypical siblings (NT siblings) of children with autism spectrum disorder (ASD) are at elevated risk for emotional distress and adjustment problems. Resiliency is the ability to cope and adapt with ongoing stressors. We conducted a randomized waitlist-controlled pilot trial to examine the feasibility, acceptability, and preliminary efficacy of an adapted virtual mind-body resiliency group intervention for teen NT siblings of children with ASD. METHODS: We modified the Stress Management and Resiliency Training-Relaxation Response Resiliency Program for NT siblings of children with ASD (SibChat). We randomly assigned teens (aged 14-17) to immediate intervention (IG) vs. waitlist control (WLC). The intervention included eight 60-minute weekly video conference group sessions. We assessed feasibility (enrollment, attendance, and retention) and acceptability (post treatment survey and weekly relaxation response practice). We explored group differences in pre-post change scores for 1) stress coping (Measure of Current Status-A) and 2) resiliency (Current Experiences Scale) using independent samples t-tests and effect size calculations. RESULTS: We enrolled 83% of screened eligible teens. 90% IG and 75% WLC participants attended at least 6/8 sessions. Among IG participants who completed the post treatment survey, 79% reported practicing relaxation response exercises at least « a few times a week ». Comparing change in baseline to time 1, the IG showed better relative changes than the WLC group in stress coping (d=0.60) and resiliency (d=0.24). CONCLUSIONS: Our pilot trial showed promising feasibility, acceptability, and preliminary efficacy of SibChat on at least one of the two primary outcomes supporting further testing of the SibChat intervention. WHAT’S NEW: This paper provides new information about an intervention designed to address resiliency and stress coping in a group of teen siblings. CLINICAL TRIAL REGISTRATION: US National Library of Medicine. REGISTRATION NUMBER: NCT04369417. https://clinicaltrials.gov/ct2/show/NCT04369417.

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8. Li J, Xu X, Liu J, Zhang S, Tan X, Li Z, Zhang J, Wang Z. Decoding microRNAs in autism spectrum disorder. Molecular therapy Nucleic acids. 2022; 30: 535-46.

Autism spectrum disorder (ASD)-a congenital mental disorder accompanied by social dysfunction and stereotyped behaviors-has attracted a great deal of attention worldwide. A combination of genetic and environmental factors may determine the pathogenesis of ASD. Recent research of multiple ASD models indicates that microRNAs (miRNAs) play a central role at the onset and progression of ASD by repressing the translation of key mRNAs in neural development and functions. As such, miRNAs show great potential to serve as biomarkers for ASD diagnosis or prognosis and therapeutic targets for the treatment of ASD. In this review, we discuss the regulatory mechanisms by which miRNAs influence ASD phenotypes through various in vivo and in vitro models, including necropsy specimens, animal models, cellular models, and, in particular, induced pluripotent stem cells derived from patients with ASD. We then discuss the potential of miRNA-based therapeutic strategies for ASD currently being evaluated in preclinical studies.

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9. Mournet AM, Wilkinson E, Bal VH, Kleiman EM. A systematic review of predictors of suicidal thoughts and behaviors among autistic adults: Making the case for the role of social connection as a protective factor. Clinical psychology review. 2022; 99: 102235.

Autistic adults are a high-risk population for suicidal thoughts and behaviors (STBs). Accordingly, this systematic review aims to review the prevalence of STBs among autistic adults, review the risk and protective factors for STBs in autistic adults, and formulate a disorder-specific conceptualization of risk in this population. We systematically searched PsycINFO and Google Scholar for all studies published prior to March 28th, 2022. We included empirical articles focused on autistic adults, ages 18 years and older, reporting on suicide-related outcomes. In total, 45 peer-reviewed empirical articles were included in the current systematic review. The most frequently studied factors in relation to suicide risk among autistic adults were interpersonal constructs (42.4% of total studies looking at risk/protective factors) and depressive symptoms (36.4% of total studies looking at risk/protective factors). We conclude by summarize two key content areas: exploring social and interpersonal constructs and better understanding the role of depressive symptoms in autism. As researchers continue to explore STBs among autistic adults, it will be necessary to addressing the overreliance on autistic symptoms instead of autism diagnoses, measurement issues of STBs, and a need for treatment adaptations.

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10. Nickels K. Childhood Neurologic Conditions: Epilepsy Management. FP essentials. 2022; 523: 15-9.

Epilepsy is the most common neurologic condition in children and is characterized by recurrent unprovoked seizures. Epilepsy can be diagnosed after a first unprovoked seizure if characteristic clinical and electroencephalographic features suggest a high risk of future seizures. Epilepsy is classified based on seizure type, underlying causes, and potential electroclinical syndromes. This classification guides management and predicts its effectiveness. Some epilepsy syndromes resolve spontaneously (ie, are self-limited) or improve with management (ie, are pharmacoresponsive). Syndromes that contribute to intellectual disability, referred to as developmental and epileptic encephalopathies, are not self-limited, are unlikely to improve with management (ie, are pharmacoresistant), and are associated with poor long-term outcomes. Antiseizure drugs are the mainstay of epilepsy management. Some broad-spectrum drugs are used to manage multiple seizure types, and others have indications for specific seizure types or epilepsy syndromes. Dietary therapy, surgical resection, and neuromodulation may be options if drugs do not control seizures. Neurodevelopmental and mental conditions are common in children with epilepsy. These include intellectual disability, learning disabilities, autism spectrum disorder, attention-deficit/hyperactivity disorder, depression, and anxiety. Patients with epilepsy should undergo screening for these associated conditions as part of routine care. Physicians should instruct caregivers and family members on how to manage seizures, including use of rescue drugs.

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11. Omori M, Yamamoto J. Segment-Unit Reading Comprehension Training for Japanese Students with Autism Spectrum Disorder and Learning Disabilities. Behavior analysis in practice. 2022; 15(3): 857-66.

Students with autism spectrum disorder (ASD) and learning disabilities (LDs) often experience reading difficulties. In particular, reading long passages can cause comprehension problems. We examined whether 8 Japanese students with ASD, 7 students with LDs, and 13 typically developing (TD) students improved their reading comprehension through two types of repeated reading training: whole-sentence-unit reading (WSUR) training and segment-unit reading (SUR) training. Participants undergoing WSUR training read whole sentences repeatedly. In SUR training, they repeatedly read a segment of a sentence in its correct spatial location. Results indicated that students with ASD and LDs showed greater improvement in reading comprehension after SUR training than after WSUR training, whereas both procedures were equally effective for TD students. Moreover, students with ASD showed only negligible reading comprehension improvements, whereas students with LDs showed intermediate improvements after WSUR training. These results suggest that sequentially presenting word segments can improve the reading comprehension of students with ASD and specific LDs.

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12. Parvaiz R, Al-Sayegh Z, Jacobsen PK, Danielsen IM, Videbech P. Validation of a screening tool for autism spectrum disorder in adults – a study protocol. Danish medical journal. 2022; 69(12).

INTRODUCTION: Autism spectrum disorder (ASD) in adults is exhibiting an increase in prevalence, and a growing rate of referrals is observed from primary health professionals to specialised units. The heterogeneous clinical presentation and high prevalence of comorbidity seen in ASD challenges the case identification, emphasising the need for screening tools with a high validity and reliability. Previously, satisfactory psychometric properties of the Ritvo Autism Asperger Diagnostic Scale – Revised (RAADS-R) have been demonstrated, and it is a widely used screening tool in Denmark. Nevertheless, a validation of a Danish version of the RAADS-R has not been performed in a Danish population. To evaluate its clinical relevance, we aim to test the psychometric properties of a Danish translation of the RAADS-R (RAADS-R-DK) in an adult population. METHODS: We aim to test 200 ASD patients, 200 non-ASD psychiatric patients and 200 healthy controls. The results from the RAADS-R will be compared with the clinical diagnoses from interdisciplinary teams at specialised outpatient clinics. CONCLUSION: The aim of the study is to investigate the validity, reliability and clinical features of the RAADS-R-DK. FUNDING: Mental Health Center Glostrup and Trygfonden. CLINICALTRIALS: gov NCT05213286.

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13. Rutten AX, Kempes M, Bongers IL, Vermeiren R, van Nieuwenhuizen C. Offence type and neurodiversity: A comparison of 12-17-year-old boys charged with a criminal offence by diagnosis of autism spectrum disorder, attention deficit hyperactivity disorder or both. Criminal behaviour and mental health : CBMH. 2022; 32(6): 404-13.

BACKGROUND: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have been evidenced as common among adolescents with delinquent behaviour. Less is known, however, about the relationship between these disorders and type of alleged offence, when the adolescent is involved with the criminal justice system. AIM: Our aim was to investigate whether the type of alleged index offences among 12-17-year-olds differ between those diagnosed with ASD, ADHD or ASD + ADHD. METHOD: The sample was selected for ASD and/or ADHD diagnoses from a database of all pre-trial forensic psychiatric and psychological assessments of male adolescents of 12-17 years old in the Netherlands for the years 2013 and 2014. For each record, independent researchers scored a 76-item checklist encompassing health and offending characteristics. Sixty-nine of the 1799 pre-trial assessments of these male adolescents had a diagnosis of ASD, 90 of ADHD and 29 had been diagnosed with both; these 188 cases formed our sample. RESULTS: The rate of sex offences was significantly higher among those with ASD (N = 20, 29%) than those with ADHD (N = 10, 11%) or both (N = 4, 14%; Fisher’s exact test = 8.54; p = 0.014). By contrast, the rate of property offences without violence was significantly higher among those with ADHD (N = 22, 24%) than those with ASD (N = 4, 6%) or both (N = 5, 17%; Fisher’s exact test = 10.50, p = 0.004), whereas violent offending rates did not differ between the three groups. CONCLUSION: Specific offence types were not equally distributed among male adolescents with different psychiatric diagnoses. In our sample of male adolescents suspected of an offence nearly one-third of those diagnosed with ASD were convicted of a sex offence, suggesting highly specialised needs for further assessment and intervention. Among those diagnosed with ADHD, significantly more adolescents were charged with non-violent property offences. Such unequal distribution of alleged offence types among adolescents with different psychiatric diagnoses justifies tailor-made attention for offending adolescents with different psychiatric diagnoses.

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14. Shields R, Kaat A, Sansone S, Michalak C, Coleman J, Thompson T, McKenzie F, Dakopolos A, Riley K, Berry-Kravis E, Widaman K, Gershon RC, Hessl D. Sensitivity of the NIH Toolbox to Detect Cognitive Change in Individuals With Intellectual and Developmental Disability. Neurology. 2022.

OBJECTIVE: Individuals with intellectual disability (ID) experience protracted cognitive development compared to typical youth. Sensitive measurement of cognitive change in this population is a critical need for clinical trials and other intervention studies, but well-validated outcome measures are scarce. This study’s aim was to evaluate the sensitivity of the NIH-Toolbox Cognitive Battery (NIHTB-CB) to detect developmental changes in groups with ID – fragile X syndrome (FXS), Down syndrome (DS), and other intellectual disability (OID) – and to provide further support for its use as an outcome measure for treatment trials. METHODS: We administered the NIHTB-CB and a reference-standard cross-validation measure (Stanford-Binet Intelligence Scales, Fifth Edition, SB5) to 256 individuals with FXS, DS, and OID (ages 6-27 years). After two years of development, we retested 197 individuals. Group developmental changes in each cognitive domain of the NIHTB-CB and SB5 were assessed using latent change score models, and two-year growth was evaluated at three age points (10, 16, and 22 years). RESULTS: Overall, effect sizes of growth measured by the NIHTB-CB tests were comparable to or exceeded those of the SB5. The NIHTB-CB showed significant gains in almost all domains in OID at younger ages (10 years), with continued gains at 16 years and stability in early adulthood (22 years). The FXS group showed delayed gains in attention and inhibitory control compared to OID. The DS group had delayed gains in receptive vocabulary compared to OID. Unlike the other groups, DS had significant growth in early adulthood in two domains (working memory and attention/inhibitory control). Importantly, each group’s pattern of NIHTB-CB growth across development corresponded to their respective pattern of SB5 growth. CONCLUSION: The NIHTB-CB is sensitive to developmental changes in individuals with ID. Comparison with levels and timing of growth on the cross-validation measure shows that the NIHTB-CB has potential to identify meaningful trajectories across cognitive domains and ID etiologies. Sensitivity to change within the context of treatment studies and delineation of clinically meaningful changes in NIHTB-CB scores, linked to daily functioning, must be established in future research to evaluate the battery more completely as a key outcome measure.

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15. Winarni TI, Sumekar TA, Sarjana W, Hardian H, Hagerman RJ, Faradz SM. The aberrant behavior profile in Indonesian individuals with fragile X syndrome with limited genetic services. Intractable & rare diseases research. 2022; 11(4): 215-8.

Fragile X syndrome (FXS) is caused by the full mutation in the fragile x messenger ribonucleoprotein 1 (FMR1) gene leading to the absence of the fragile X protein (FXP). Previous studies show that individuals with FXS exhibit changing behavior over time; therefore, this study aimed to elucidate the aberrant behavior profile of FXS individuals. The Aberrant Behavior Checklist-Community (ABC-C) was used to measure the aberrant behavior profile of individuals with FXS, which was rated by the parent/caregiver combined with clinical impression. A total of 58 items were used to assess aberrant behaviors across five subscales. Forty-nine individuals with FXS were included (32 males, 17 females) with a mean age of 32.9 ± 14.62 years in males and 33.4 ± 13.98 years in females. The average score of irritability and hyperactivity was significantly higher in male FXS individuals (5.37 ± 6.231 and 10.28 ± 8.524) than in female individuals (3.24 ± 7.093 and 3.76 ± 3.327) with p = 0.046 and p = 0.001, respectively. Overall irritability in FXS individuals significantly decreased over time (ß = -0.141; p = 0.032). A modest worsening in lethargy/social withdrawal in males across age and a gentle improvement in hyperactivity/noncompliance in male of FXS individuals were observed. FXS males had higher hyperactivity problems than FXS female individuals across age.

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16. Wodziński M, Rządeczka M, Moskalewicz M. How to Minimize the Impact of Experts’ Non-rational Beliefs on Their Judgments on Autism. Community mental health journal. 2022: 1-14.

The non-autistic majority often judges people on the autism spectrum through the prism of numerous stereotypes, prejudices, cognitive biases, or, generally speaking, non-rational beliefs. This causes problems in autistic people’s everyday lives, as they often feel stigmatized, marginalized, and they internalize deficit-laden narratives about themselves. Unfortunately, experts, including health or law professionals, are not entirely immune to these non-rational beliefs, which affect their decision-making processes. This primarily happens when a mix of background knowledge, overconfidence, and haste co-occur. The resulting decisions may impact autistic people, e.g., by determining eligibility for the state’s therapeutical and financial support. This paper shows how simplified reasoning and inference may influence experts’ (medical examiners or court expert witnesses) decision-making processes concerning autistic people. It also proposes particular clues and strategies that could help experts cope with this risk and avoid making biased decisions.

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17. Zhao YV, Gibson JL. Solitary symbolic play, object substitution and peer role play skills at age 3 predict different aspects of age 7 structural language abilities in a matched sample of autistic and non-autistic children. Autism & developmental language impairments. 2022; 7: 23969415211063822.

BACKGROUNDS AND AIMS: Early symbolic play abilities are closely related to long-term language development for both autistic and non-autistic children, but few studies have explored these relations for different dimensions of pretence and of language. The current study explores carer-reported measures of solitary symbolic play, object substitution and peer role play abilities at age 3, and their respective relations with parent-reported semantics, syntax and narrative abilities at age 7 for both autistic and non-autistic children. METHODS: We conducted secondary data analyses exploring links between different aspects of pretence and of language on the Longitudinal Study of Australian Children population cohort. We identified 92 autistic children and used propensity score matching to match them with 92 non-autistic children based on demographic and developmental information such as non-verbal IQ and socioeconomic status. We explored concurrent and longitudinal relations using correlation and regression models. Results: Both correlational and hierarchical regression analyses confirmed the significant effects of age 3 symbolic play abilities in facilitating age 7 semantics, syntax and narrative abilities for autistic children. We found that object substitution held most prominent influence, followed by peer role play and solitary symbolic play. In contrast, for non-autistic children, none of the age 3 symbolic play abilities were significant predictors, whereas socioeconomic status at birth and age 3 language abilities held significant influences on their age 7 semantics, syntax and narrative abilities. Conclusion: We discuss the implications of our findings for play interventions targeting language outcomes.

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