Autistic Behavior Research Articles

Characteristics of Individuals Losing Autism Diagnosis: A Comparative Study With Typically Developing and Autism Spectrum Disorder Individuals.

This study aims to reveal the characteristics of individuals who have lost an autism spectrum disorder (ASD) diagnosis and to evaluate their current psychiatric diagnoses. Additionally, the study aims to compare individuals who have lost ASD with typically developing (TD) individuals and those with ASD in terms of current psychopathology, functionality and sociodemographic and clinical variables. The study included a total of 85 participants aged between 5 and 18, comprising 30 individuals who no longer meet the criteria for ASD (loss of autism diagnosis or LAD), 32 individuals with ASD and 23 TD individuals. While the sociodemographic data form and Childhood Autism Rating Scale (CARS) were completed by the clinician, the Autism Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) were completed by the parents. It was found that the LAD group acquired speaking skills earlier, started special education sooner, received preschool education and physical exercise support for a longer duration and exhibited higher mental capacity and lower symptom severity compared to the ASD group. Moreover, 80% of the LAD group had at least one DSM-5 diagnosis. Scores on the ABC and SRS indicated a significant difference, with ASD > LAD > TD. Even if ASD regresses, individuals may still experience residual difficulties and remain at risk for other psychopathologies. Therefore, it is crucial to maintain monitoring and support processes.

Autism Training for Law Enforcement Officers: Perceptions From the Field.

Autistic individuals and law enforcement officers are likely to engage under various circumstances within the community. Therefore, law enforcement officers require training on supporting those with autism and better understanding autistic behaviors. Aims for this study include: (1) developing and delivering high quality professional development on autism spectrum disorder (ASD) to support autistic individuals during encounters with law enforcement officers, and (2) examining how law enforcement officers respond to the professional development session. For this study a four-hour, in-person training on autism for law enforcement officers was developed. Law enforcement officers (n = 27) attended the training session. Subsequently, participants completed an open-ended survey gathering perceptions related to the topics covered in the training, thoughts on the feasibility and applicability of content, and transfer to future safety encounters involving autistic individuals. Data was analyzed using a qualitative approach including concept driven thematic coding with constant comparisons. Data yielded themes on experiences with the autistic community, strategies learned from the training, thoughts on specific content, and feedback on the training format. Overall, law enforcement officers reported they felt better prepared, more knowledgeable on the autistic community, and believed the strategies were feasible and applicable to the field. These findings point to the importance of training on autism and that law enforcement officers found it was time well spent. Future directions include examining how training transfers to practice in the field and ways to connect law enforcement officers with the autistic community outside of emergency response.

Efficacy and safety of JNJ-42165279, a fatty acid amide hydrolase inhibitor, in adolescents and adults with autism spectrum disorder: a randomized, phase 2, placebo-controlled study.

JNJ-42165279, a highly selective and orally bioavailable fatty acid amide (FAA) hydrolase inhibitor, was evaluated for efficacy and safety in adolescents and adults with autism spectrum disorder (ASD) in this phase 2, double-blind, placebo-controlled, multicenter study (NCT03664232). Participants aged 13-35 years, with a diagnosis of ASD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; Autism Diagnostic Observation Schedule, 2nd edition) were randomized (1:1) to 12 weeks of treatment with JNJ-42165279 (25 mg, twice-daily) or placebo. Primary endpoints were the change in the Autism Behavior Inventory (ABI) Core Domain (ABI-CD), ABI-Social Communication (ABI-SC), and ABI-Repetitive/Restrictive Behavior (ABI-RB) scores from baseline to day 85. Of the 61 participants (16 female, 45 male) included in the efficacy analyses, 53 (87%) completed the double-blind treatment. At day 85, the JNJ-42165279 group did not show a statistically significant reduction in ASD symptoms versus placebo, as assessed with ABI-CD (p = 0.284), ABI-SC (p = 0.290), and ABI-RB (p = 0.231). However, the following secondary outcomes exhibited small to moderate changes directionally favoring JNJ-42165279: Social Responsiveness Scale 2 (SRS, p = 0.064), Repetitive Behavior Scale-Revised (RBS-R, p = 0.006), Zarit Burden Interview short version (ZBI, p = 0.063), Child Adolescent Symptom Inventory-Anxiety (CASI-Anx, p = 0.048), and Caregiver Global Impression of Severity (p = 0.075). Notably, versus placebo, JNJ-42165279-treated participants showed increased concentrations of FAAs throughout the treatment period, with those achieving elevated concentrations experiencing the greatest reduction in the SRS total score at day 85. JNJ-42165279 demonstrated an acceptable safety profile. Although primary endpoints were not met, JNJ-42165279 may have a therapeutic effect on certain aspects of core ASD symptoms.

A prospective randomized controlled study of neurofeedback combined with learning style profile intervention training in children with high-functioning autism

To explore the application of neurofeedback (NFB) combined with learning style profile (LSP) intervention training in children with high-functioning autism (HFA). A prospective study was conducted to select 86 children with HFA admitted to the hospital from February 2022 to February 2024. They were divided into two groups according to the random number table method, with 43 cases in each group. In this double-blind study, the control group was given LSP intervention training, and the observation group was given NFB intervention on the basis of the treatment used in the control group. Both groups were treated for 6 months. The scores of Autism Behavior Checklist (ABC), Autism Treatment Evaluation Checklist (ATEC), Social Responsiveness Scale (SRS), and Pediatric Quality of Life (PedsQL) were compared between the two groups before intervention and at 6 months after intervention. The relationship of PedsQL score with ABC, ATEC, and SRS scores was analyzed in children with HFA. After 6 months of intervention, the scores of ABC, ATEC, and SRS in the observation group were significantly lower than those in the control group, while the PedsQL score in the observation group was significantly higher than that in the control group (P<0.05). The PedsQL score was negatively correlated with the ABC, ATEC, and SRS scores in children with HFA (r=-0.238, -0.381, -0.219 respectively; P<0.001). NFB combined with LSP can effectively improve the clinical symptoms and social ability, control the development of the disease, and improve the quality of life in children with HFA.

Thumbtack needle at front-mu points for abnormal behavior in children with autism spectrum disorders

To compare the clinical effect of thumbtack needle at front-mu points combined with conventional rehabilitation training and simple conventional rehabilitation training in the treatment of autism spectrum disorders (ASD). A total of 40 children with ASD were randomly divided into a combination group (20 cases, 3 cases dropped out) and a conventional rehabilitation group (20 cases, 3 cases dropped out). Conventional rehabilitation training i.e. language-cognition training and comprehensive education training was adopted in the conventional rehabilitation group, once a day, 5 days a week. On the basis of the treatment in the conventional rehabilitation group, thumbtack needle was applied at Zhongwan (CV 12), bilateral Tianshu (ST 25) and Guanyuan (CV 4) in the combination group, the needles were retained for 3 days each time, 3-day interval was taken between each treatment, for 5 times per month. One-month treatment was as one course and a total of 3 courses were required in both groups, with 10-day break between each course. Before and after treatment, the scores of autism behavior checklist (ABC), childhood autism rating scale (CARS), TCM spleen-stomach symptoms and Achenbach child behavior checklist (CBCL) were observed, and the serum ratio of glutamate and gamma-aminobutyric acid (Glu/GABA) was measured. After treatment, the scores of ABC, CARS and CBCL were decreased compared with those before treatment (P<0.05, P<0.01) in both groups, the TCM spleen-stomach symptoms score was decreased compared with that before treatment (P<0.05) in the combination group; the changes in the scores of ABC, CARS, TCM spleen-stomach symptoms and CBCL, as well as the serum Glu/GABA in the combination group were lager than those in the conventional rehabilitation group (P<0.05, P<0.01). Both thumbtack needle at front-mu points combined with conventional rehabilitation training and simple conventional rehabilitation training can effectively treat ASD, the combination treatment has superior effect on improving the abnormal behavior, spleen-stomach symptoms and balance of nerve impulse and inhibition.

Cermin diri akuntan forensik dibalik keistimewaannya sebagai pengidap autistik: Analisis wacana kritis film the accountant

This study aims to reveal the relationship between autistic behavior and the basic characteristics that forensic accountants need to have. This research uses a critical discourse analysis method. Critical discourse analysis was carried out on the research object of the film "The Accountant". This study found that there are characteristics of autism that are in accordance with the basic characteristics that forensic accountants need to have. The basic characteristics that need to be possessed by forensic accountants which are also possessed by people with autism include being independent and objective. The nature of autism that makes a person have an indifferent attitude towards the environment can actually be used as a factor for the success of forensic accountants. This research opens up views on autistic people who also have potential in the field of forensic accounting. This study also invites readers not to underestimate people who have autism. The novelty in this study is the object of research that focuses on forensic accounting from the point of view of people with autistic disorders.

Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study.

Environmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. In 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004-2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n=179), paternal preconception (n=122), and maternal pregnancy (n=177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. The mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (βmaternal_precon = -1.6, 95% CI -2.7; -0.4; βpaternal_precon = -2.9, 95% CI -4.6; -1.2) for each loge increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. Urinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

Second Case of Gonadal Mosaicism and a Novel Nonsense NR2F1 Gene Variant as the Cause of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome.

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disease characterized by developmental delay, intellectual disability, and optic atrophy with a variable expression of other clinical features (dysmorphic features, autistic behaviour, corpus callosum hypoplasia and seizures). To date, approximately a hundred cases of the syndrome have been described, with an estimated prevalence of 1 in 100 000-250 000. BBSOAS is caused by the loss of function of the NR2F1 gene (nuclear receptor subfamily 2 group F member 1), which encodes the COUP-TFI (Chicken ovalbumin upstream promotor-transcription factor 1). COUP-TFI functions as a homodimer and is one of the major transcriptional regulators directing cortical arealization, cell differentiation and maturation. Most cases of BBSOAS occur de novo, and one case was previously described in which the disease resulted from gonadal mosaicism. In the present case, we report two sisters with BBSOAS, a novel nonsense mutation in the NR2F1 gene and potential gonadal mosaicism as the cause of this rare disease, making it the second such case described in the literature.

Genetic Variations and Serum Levels of Leptin and Ghrelin in Autism Spectrum Disorder.

This study aims to examine leptin and ghrelin gene polymorphisms and serum levels in children with autism spectrum disorder (ASD). The study comprised a case group of 40 children aged 2-7 diagnosed with ASD and a control group of 40 healthy children. The severity of ASD symptoms was assessed using the Childhood Autism Rating Scale and the Autism Behavior Checklist. Leptin and ghrelin gene variants were genotyped using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Serum ghrelin and leptin levels were measured using enzyme-linked immunosorbent assay kits. In this study, gene polymorphisms and allele frequencies were examined, and no significant difference was found (P > .05 for all). Our findings indicated no significant difference in leptin serum levels between the groups (P = .584). However, ghrelin serum levels were significantly lower in the ASD group (P = .027). Receiver operating curve analysis to determine the cutoff value of serum ghrelin level as a diagnostic indicator for ASD resulted in a cutoff value of 885.7 pg/mL with 42.50% sensitivity and 85% specificity (P = .021). No significant relationship was found between leptin and ghrelin serum levels and the severity of ASD (P > .05 for all). Our study is the first to evaluate leptin and ghrelin gene polymorphisms in ASD. Our findings indicate no association between leptin and ghrelin gene polymorphisms and ASD. However, our study suggests that ghrelin serum levels may potentially contribute to the etiology of ASD. More research is needed to understand the role of leptin and ghrelin in ASD.

Decreased levels of L‐selectin and platelet‐endothelial cell adhesion molecule‐1 in children with autism spectrum disorder

AbstractObjectiveThis study aimed to ascertain the serum levels of selectins (E, L, P) and platelet‐endothelial adhesion molecule‐1 (PECAM‐1) in preschool children with autism spectrum disorder (ASD) and to establish a comparison with the levels observed in healthy controls.MethodsThe study included 34 children aged 2–7 years diagnosed with ASD (ASD group) and 34 randomly selected healthy children matched for age and sex to the ASD group. The children were free of any genetic or physical disease, clinically active infection, or medication use. The sociodemographic data form was completed by all parents. The Childhood Autism Rating Scale (CARS) and the Autism Behavior Checklist (ABC) were administered to the patient group, and the Aberrant Behavior Checklist (AbBC) was completed by the families of all children. Serum selectin (E, L, P) and PECAM‐1 levels were measured using enzyme‐linked immunosorbent assay (ELISA) kits.ResultsThe results showed that the levels of both L‐selectin (p = 0.007) and PECAM‐1 (p = 0.019) were significantly lower in the ASD group than in the control group. No significant difference was observed between the groups concerning E‐selectin and P‐selectin levels (p &gt; 0.05). It was observed that P‐selectin variables were statistically significant in predicting the presence of ASD (p = 0.019). A remarkable inverse correlation was found between the AbBC irritability subscale score and L‐selectin (r = −0.296, p = 0.014) and PECAM‐1 (r = −0.276, p = 0. 023); the AbBC Lethargy‐Social Withdrawal subscale score and E‐Selectin (r = −0.239, p = 0.049), L‐Selectin (r = −0.297, p = 0.014) and PECAM‐1 (r = −0.264, p = 0.029); L‐Selectin levels and the AbBC stereotypic behavior subscale (r = −0.248, p = 0.042). No statistically significant relationship was observed between selectins (E, L, P) and PECAM‐1 levels and CARS scale, ABC subscale or total scores and age variables (p &gt; 0.05).ConclusionsThese study results suggest that L‐selectin, P‐selectin and PECAM‐1 may play a role in the pathophysiology of ASD.

Differential item functioning in the autism behavior checklist in children with autism spectrum disorder based on a machine learning approach.

Our study utilized the Rasch analysis to examine the psychometric properties of the Autism Behavior Checklist (ABC) in children with autism spectrum disorder (ASD). A total of 3,319 children (44.77 ± 23.52 months) were included. The Rasch model (RM) was utilized to test the reliability and validity of the ABC. The GPCMlasso model was used to test the differential item functioning (DIF). The response pattern of this sample showed acceptable fitness to the RM. The analysis supported the unidimensionality assumption of the ABC. Disordered category functions and DIF were found in all items in the ABC. The participants responded to the ABC items differently depending not only on autistic traits but also on age groups, gender, and symptom classifications. The Rasch analysis produces reliable evidence to support that the ABC can precisely depict clinical ASD symptoms. Differences in population characteristics may cause unnecessary assessment bias and lead to overestimated or underestimated symptom severity. Hence, special consideration for population characteristics is needed in making an ASD diagnosis.

Clinical features and genetic analysis of four children with Phelan-McDermid syndrome

To explore the clinical characteristics and genetic etiology of four children with Phelan-McDermid syndrome (PMS). Four children who had visited the Ningbo Women and Children's Hospital between June 2, 2022 and May 8, 2023 were selected as the study subjects. Clinical data of the children were collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and quantitative PCR (q-PCR) analysis. All children had presented with speech and language delays and intellectual disability. Children 3 and 4 also presented with autistic behaviors. WES showed that the children 1 and 2 had respectively carried a heterozygous c.731T>C (p.Leu244Pro) and a c.2782_2851del (p.Gly928ArgfsTer4) variant of the SHANK3 gene. Sanger sequencing confirmed that their parents did not carry the same variant, suggesting that they were de novo in origin. Children 3 and 4 had respectively harbored a 121 Kb and 52.02 Kb heterozygous deletion at chromosome 22q13.33, which had both encompassed the SHANK3 and ACR genes mapped to 22q13.33. q-PCR results showed that the deletion of SHANK3 and ACR genes were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.731T>C and c.2782_2851del variants were predicted to be likely pathogenic (PS2+PM2_Supporting+PP3) and pathogenic (PVS1+PM2_Supporting+PS2_Supporting), respectively. Furthermore, the 52.02 Kb and 121 Kb heterozygous deletions in 22q13.33 were both predicted to be pathogenic (2D+4C, 1.05 in score; 2D+4C, 1 in score). The four children were all diagnosed with PMS by genetic testing. Above finding has enriched the phenotypic and mutational spectrum of PMS, and provided a basis for clinical diagnosis and genetic counseling for their families.

Mutations in the U2 snRNA gene RNU2-2P cause a severe neurodevelopmental disorder with prominent epilepsy.

The major spliceosome comprises the five snRNAs U1, U2, U4, U5 and U6. We recently showed that mutations in RNU4- 2, which encodes U4 snRNA, cause one of the most prevalent monogenic neurodevelopmental disorders. Here, we report that recurrent germline mutations in RNU2-2P , a 191bp gene encoding U2 snRNA, are responsible for a related disorder. By genetic association, we implicated recurrent de novo single nucleotide mutations at nucleotide positions 4 and 35 of RNU2-2P among nine cases. We replicated this finding in six additional cases, bringing the total to 15. The disorder is characterized by intellectual disability, neurodevelopmental delay, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype. Our findings cement the role of major spliceosomal snRNAs in the etiologies of neurodevelopmental disorders.

Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial.

The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD. We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16. Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms. BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.

Rubinstein-Taybi Syndrome Clinical Characteristics from the Perspective of Quality of Life and the Impact of the Disease on Family Functioning.

Background/Objectives: Rubinstein-Taybi Syndrome (RSTS-OMIM, #180849) is a rare genetic disorder associated with distinctive clinical features, including a typical craniofacial appearance, global developmental delay, intellectual disability and broad, angular thumbs and fingers. The main aim of the study was to evaluate the health problems of children with RTST, their quality of life and the impact of the disease on family functioning. In addition, we investigate whether comorbidities, autistic behavior and eating problems affect the children's overall QOL. Methods: A cross-sectional study was performed, including a total of 13 caregivers of children diagnosed with RSTS. A self-reported questionnaire [SRQ], medical records and the Pediatric Impact Module PedsQLTM 2.0, the Pediatric Quality of Life PedsQLTM 4.0 were used to obtain data on QOL and the impact of the disease on family functioning. Results: The overall QOL score for children with RSTS was x = 52.40; SD 13.01. The highest QOL was in emotional functioning (EF; x = 59.23; SD 18.69), while the lowest QOL was in physical functioning (PF; x = 48.56; SD 16.32) and social functioning (SF; x = 48.85; SD 18.84). There was a statistically significant negative correlation (p < 0.03; r = -2.01) between the age of the child and their QOL, indicating that older children had lower QOL scores. The mean overall rating for the impact of RSTS on family functioning was x = 50.00; SD 10.91. Caregivers reported the highest scores for cognitive functioning (CF; x = 64.23; SD 23.70) and family relationships (FR; x = 60.00; SD 17.17). The lowest scores were for daily activities (DA; x = 41.03; SD 17.17) and worry (W; x = 37.69; SD 18.55). Conclusions: This study provides the first comprehensive exploration of the QOL of children with RSTS) and its impact on family functioning.

Vasostatin-1 restores autistic disorders in an idiopathic autism model (BTBR T+ Itpr3tf/J mice) by decreasing hippocampal neuroinflammation

Chromogranin A (CgA), a ∼ 49 kDa acidic secretory protein, is ubiquitously distributed in endocrine and neuroendocrine cells and neurons. As a propeptide, CgA is proteolytically cleaved to generate several peptides of biological importance, including pancreastatin (PST: hCgA250–301), Vasostatin 1 (VS1: hCgA1–76), and catestatin (CST: CgA 352–372). VS1 represents the most conserved fragment of CgA. A 20 amino acid domain within VS1 (CgA 47–66) exhibits potent antimicrobial and anti-inflammatory activities. Autism is known to be associated with inflammation. Therefore, we seek to test the hypothesis that VS1 modulates autism behaviors by reducing inflammation in the hippocampus. Treatment of C57BL/6 (B6) and BTBR (a mouse model of idiopathic autism) mice with VS1 revealed the following: BTBR mice showed a significant decrease in chamber time in the presence of a stranger or a novel object. Treatment with VS1 significantly increased chamber time in both cases, underscoring a crucial role for VS1 in improving behavioral deficits in BTBR mice. In contrast to chamber time, sniffing time in BTBR mice in the presence of a stranger was less compared to B6 control mice. VS1 did not improve this latter parameter. Surprisingly, sniffing time in BTBR mice in the presence of a novel object was comparable with B6 mice. Proinflammatory cytokines such as IL-6 and IL-1b, as well as other inflammatory markers, were elevated in BTBR mice, which were dramatically reduced after supplementation with VS1. Interestingly, even Beclin-1/p62, pAKT/AKT, and p-p70-S6K/p70-S6K ratios were notably reduced by VS1. We conclude that VS1 plays a crucial role in restoring autistic spectrum disorders (ASD) plausibly by attenuating neuroinflammation.

Experimentally altering microRNA levels in embryos alters adult phenotypes

We previously identified a unique genetic feature of Autism Spectrum Disorder (ASD) in human patients and established mouse models, a low to very low level of six microRNAs, miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p and miR-499a-5p. We attempted to interfere experimentally in mice with two of them, miR19a-3p and miR499a-5p by microinjecting into zygote pronuclei either the complementary sequence or an excess of the microRNA. Both resulted in low levels in the tissues and sperm of the targeted microRNAs and their pri and pre precursors. This method stably modify predetermined levels of miRNAs and identify miRNA alterations that cause changes in autistic behavior and predispose the individual to an inherited disease. Excess miRNA results in single-stranded miRNA variations in both free and DNA-bound RNA (R-loop) fractions in mouse models thus appearing to affect their own transcription. Analysis of miRNAs fractions in human patients blood samples confirm low level of six microRNAs also in R-loop fractions.

Gestational environmental chemical mixtures, folate, and child autistic behaviors in a Canadian pregnancy and birth cohort

Gestational environmental chemical mixtures, folate, and child autistic behaviors in a Canadian pregnancy and birth cohort

A Genotype/Phenotype Study of KDM5B-Associated Disorders Suggests a Pathogenic Effect of Dominantly Inherited Missense Variants.

Bi-allelic disruptive variants (nonsense, frameshift, and splicing variants) in KDM5B have been identified as causative for autosomal recessive intellectual developmental disorder type 65. In contrast, dominant variants, usually disruptive as well, have been more difficult to implicate in a specific phenotype, since some of them have been found in unaffected controls or relatives. Here, we describe individuals with likely pathogenic variants in KDM5B, including eight individuals with dominant missense variants. This study is a retrospective case series of 21 individuals with variants in KDM5B. We performed deep phenotyping and collected the clinical information and molecular data of these individuals' family members. We compared the phenotypes according to variant type and to those previously described in the literature. The most common features were developmental delay, impaired intellectual development, behavioral problems, autistic behaviors, sleep disorders, facial dysmorphism, and overgrowth. DD, ASD behaviors, and sleep disorders were more common in individuals with dominant disruptive KDM5B variants, while individuals with dominant missense variants presented more frequently with renal and skin anomalies. This study extends our understanding of the KDM5B-related neurodevelopmental disorder and suggests the pathogenicity of certain dominant KDM5B missense variants.

Performance of the Social Responsiveness Scale-2 for the Assessment of Autistic Behaviors in a Sample of Canadian Preschool-Aged Children.

Behavioral traits of autism spectrum disorder (ASD) typically present in early childhood, underscoring the importance of screening tools for the early identification of ASD. The current study compared scores on the Social Responsiveness Scale-Second Edition (SRS-2) Preschool Form between the US standardization sample (n = 247) and a Canadian cohort of preschool-aged children (n = 595) recruited from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. In the MIREC sample, we examined whether ASD-like traits are correlated with sociodemographic characteristics and child intellectual abilities, and how maternal ratings of social skills assessed by the SRS-2 are associated with maternal ratings of general problem behaviors. Mean total SRS-2 raw score was significantly lower in the MIREC sample (mean = 29.7, SD = 15.8) compared to the US standardization sample (mean = 41.9, SD = 26.0). Total raw score in the US standardization sample did not significantly differ between males (mean = 40.6, SD = 23.1) and females (mean = 42.8, SD = 28.7), whereas in the MIREC sample the total raw score was significantly higher among males (mean = 33.0, SD = 17.1) than females (mean = 26.6, SD = 13.9). A significantly larger proportion of the MIREC sample was White, younger in age, and had more educated parents compared to the US standardization sample. ASD-like traits were correlated with lower intellectual abilities, a less enriched home environment, more behavioral problems, and poorer adaptive skills. SRS-2 Preschool Form scores were significantly lower in the Canadian sample compared to the US standardization sample, which may reflect demographic differences between the two groups. Girls may be under-identified when SRS-2 Preschool Form norms are used for screening ASD.