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Biology Jun 2024Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (>200 CGG...
Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (>200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 () gene. Individuals with FXS experience various challenges related to social interaction (SI). Animal models, such as the model for FXS where the only ortholog of human () is mutated, have played a crucial role in the understanding of FXS. The aim of this study was to investigate SI in the mutants (the groups of flies of both sexes simultaneously) using the novel Drosophila Shallow Chamber and a Python data processing pipeline based on social network analysis (SNA). In comparison with wild-type flies (), SNA analysis in mutants revealed hypoactivity, fewer connections in their networks, longer interaction duration, a lower ability to transmit information efficiently, fewer alternative pathways for information transmission, a higher variability in the number of interactions they achieved, and flies tended to stay near the boundaries of the testing chamber. These observed alterations indicate the presence of characteristic strain-dependent social networks in flies, commonly referred to as the group phenotype. Finally, combining novel research tools is a valuable method for SI research in fruit flies.
PubMed: 38927312
DOI: 10.3390/biology13060432 -
Scientific Reports Jun 2024Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations...
Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required. Detection of ADNP by means of western blotting has been ambiguous with reported antibodies resulting in non-specific bands without unique ADNP signal. Validation of an N-terminal ADNP antibody (Aviva Systems) using a blocking peptide competition assay allowed to differentiate between specific and non-specific signals in different sample materials, resulting in a unique band signal around 150 kDa for ADNP, above its theoretical molecular weight of 124 kDa. Detection with different C-terminal antibodies confirmed the signals at an observed molecular weight of 150 kDa. Our antibody panel was subsequently tested by immunoblotting, comparing parental and homozygous CRISPR/Cas9 endonuclease-mediated Adnp knockout cell lines and showed disappearance of the 150 kDa signal, indicative for intact ADNP. By means of both a GFPSpark and Flag-tag N-terminally fused to a human ADNP expression vector, we detected wild-type ADNP together with mutant forms after introduction of patient mutations in E. coli expression systems by site-directed mutagenesis. Furthermore, we were also able to visualize endogenous ADNP with our C-terminal antibody panel in heterozygous cell lines carrying ADNP patient mutations, while the truncated ADNP mutants could only be detected with epitope-tag-specific antibodies, suggesting that addition of an epitope-tag possibly helps stabilizing the protein. However, western blotting of patient-derived hiPSCs, immortalized lymphoblastoid cell lines and post-mortem patient brain material failed to detect a native mutant ADNP protein. In addition, an N-terminal immunoprecipitation-competent ADNP antibody enriched truncating mutants in overexpression lysates, whereas implementation of the same method failed to enrich a possible native mutant protein in immortalized patient-derived lymphoblastoid cell lines. This study aims to shape awareness for critical assessment of mutant ADNP protein analysis in Helsmoortel-Van der Aa syndrome.
Topics: Humans; Homeodomain Proteins; Nerve Tissue Proteins; Mutation; HEK293 Cells; Autism Spectrum Disorder; Heart Diseases; Facies; Neurodevelopmental Disorders
PubMed: 38926592
DOI: 10.1038/s41598-024-65608-x -
Pediatric Research Jun 2024Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are the most prevalent neurodevelopmental disorders. There is a growing body of... (Review)
Review
Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are the most prevalent neurodevelopmental disorders. There is a growing body of literature investigating factors affecting quality of life in families (FQoL) with a child with these disorders. However, there are no studies that trace their knowledge anatomy. Thus, we conducted a scientometric analysis to describe this literature, detect certain variables that could be related to FQoL, and identify tendencies and open questions for future research. A literature search in the Web of Science, PubMed, and Scopus was run and identified 3281 publications published between 1975 and 2022. The results suggest an increase in the quantity of publications on FQoL in ASD and ADHD over the last few years (14% and 12%, respectively). For both research fields, the USA published the highest number of documents, showing that the production related to ADHD and FQoL is concentrated in just a few countries. Thematic analysis revealed several clusters, considering quality of life and children as core themes that are still setting trend lines. Moreover, it would be worthwhile to describe and analyze FQoL not only during the childhood of children with ASD and ADHD but also during their adolescence. IMPACT: Although the relationship between family quality of life and neurodevelopmental disorders could be considered novel, there is a growing interest from an interdisciplinary perspective. Family quality of life should be monitored not only during the childhood of children with ASD and ADHD, but also during their adolescence and adulthood. The analysis of the family quality of life in first-degree relatives and its relationship with protective factors (e.g., resilience and social support) should be explored in future studies.
PubMed: 38926550
DOI: 10.1038/s41390-024-03350-w -
Scientific Reports Jun 2024ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early...
ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early psychosocial exposures related to later diagnosis of ADHD, ASD, and their co-occurrence. 16,365 children born 1997-1999 and their families, involved in the prospective population-based ABIS study (All Babies in Southeast Sweden), were included in this sub-study. Pre and perinatal factors and early environmental psychosocial exposures were collected from parental-questionnaires at birth and 1-year follow-up. Diagnoses from birth up to 23 years of age were obtained from the Swedish National Diagnosis Register in 2020. The cumulative incidence of ADHD, ASD, and their co-occurrence in the ABIS-cohort Study were 4.6%, 1.7%, and 1.1%, respectively. Being male was associated with an increased risk for ADHD, ASD, and their co-occurrence (aOR 1.30, 1.56, and 1.91, respectively), while higher household income reduced it (aOR 0.82, 0.73, and 0.64). Serious life events during pregnancy (aOR 1.40) and maternal smoking (aOR 1.51) increased the risk of ADHD, while older maternal age (aOR 0.96), higher parental education (aOR 0.72 maternal and aOR 0.74 paternal) and longer exclusive breastfeeding (aOR 0.72) reduced it. Non-Swedish paternal nationality (aOR 0.40) and higher maternal education (aOR 0.74) were associated with a lower risk of ASD, while a family history of autoimmune diseases increased the risk of the co-occurrence of both disorders (aOR 1.62). Obtained results suggest that the etiology of ADHD, ASD, and their co-occurrence is independently associated with environmental psychosocial predictors. The co-occurrence seems to overlap the etiology of ADHD, in which psychosocial determinants have a larger role, however, it is also independently influenced by a family history of autoimmune diseases.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Female; Male; Prospective Studies; Child; Sweden; Risk Factors; Child, Preschool; Pregnancy; Infant; Adolescent; Adult; Infant, Newborn; Young Adult; Incidence; Prenatal Exposure Delayed Effects
PubMed: 38926504
DOI: 10.1038/s41598-024-65067-4 -
Scientific Reports Jun 2024Accommodating talker variability is a complex and multi-layered cognitive process. It involves shifting attention to the vocal characteristics of the talker as well as...
Accommodating talker variability is a complex and multi-layered cognitive process. It involves shifting attention to the vocal characteristics of the talker as well as the linguistic content of their speech. Due to an interdependence between voice and phonological processing, multi-talker environments typically incur additional processing costs compared to single-talker environments. A failure or inability to efficiently distribute attention over multiple acoustic cues in the speech signal may have detrimental language learning consequences. Yet, no studies have examined effects of multi-talker processing in populations with atypical perceptual, social and language processing for communication, including autistic people. Employing a classic word-monitoring task, we investigated effects of talker variability in Australian English autistic (n = 24) and non-autistic (n = 28) adults. Listeners responded to target words (e.g., apple, duck, corn) in randomised sequences of words. Half of the sequences were spoken by a single talker and the other half by multiple talkers. Results revealed that autistic participants' sensitivity scores to accurately-spotted target words did not differ to those of non-autistic participants, regardless of whether they were spoken by a single or multiple talkers. As expected, the non-autistic group showed the well-established processing cost associated with talker variability (e.g., slower response times). Remarkably, autistic listeners' response times did not differ across single- or multi-talker conditions, indicating they did not show perceptual processing costs when accommodating talker variability. The present findings have implications for theories of autistic perception and speech and language processing.
Topics: Humans; Male; Female; Adult; Speech Perception; Autistic Disorder; Young Adult; Reaction Time; Speech; Attention; Middle Aged; Language
PubMed: 38926416
DOI: 10.1038/s41598-024-62429-w -
[Neurodevelopment and cerebral blood flow in children aged 2-6 years with autism spectrum disorder].Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the neurodevelopmental characteristics of children with autism spectrum disorder (ASD), analyze the correlation between neurodevelopmental indicators and...
OBJECTIVES
To investigate the neurodevelopmental characteristics of children with autism spectrum disorder (ASD), analyze the correlation between neurodevelopmental indicators and cerebral blood flow (CBF), and explore the potential mechanisms of neurodevelopment in ASD children.
METHODS
A retrospective study was conducted on 145 children aged 2-6 years with newly-diagnosed ASD. Scores from the Gesell Developmental Diagnosis Scale and the Autism Behavior Checklist (ABC) and CBF results were collected to compare gender differences in the development of children with ASD and analyze the correlation between CBF and neurodevelopmental indicators.
RESULTS
Fine motor and personal-social development quotient in boys with ASD were lower than those in girls with ASD (<0.05). Gross motor development quotient in ASD children was negatively correlated with CBF in the left frontal lobe (=-0.200, =0.016), right frontal lobe (=-0.279, =0.001), left parietal lobe (=-0.208, =0.012), and right parietal lobe (=-0.187, =0.025). The total ABC score was positively correlated with CBF in the left amygdala (=0.295, <0.001).
CONCLUSIONS
Early intervention training should pay attention to gender and developmental structural characteristics for precise intervention in ASD children. CBF has the potential to become a biological marker for assessing the severity of ASD.
Topics: Humans; Male; Autism Spectrum Disorder; Female; Child, Preschool; Child; Cerebrovascular Circulation; Retrospective Studies; Child Development
PubMed: 38926376
DOI: 10.7499/j.issn.1008-8830.2401048 -
Journal of Assisted Reproduction and... Jun 2024Techniques of medically assisted reproduction interact with the embryo at crucial developmental stages, yet their impact on the fetus and subsequent child's health...
PURPOSE
Techniques of medically assisted reproduction interact with the embryo at crucial developmental stages, yet their impact on the fetus and subsequent child's health remains unclear. Given rising infertility rates and more frequent use of fertility treatments, we aimed to investigate if these methods heighten the risk of autism spectrum disorder (ASD) in children.
METHODS
A population-based cohort study was conducted at Soroka University Medical Center, a tertiary referral hospital, encompassing singleton births. The incidence of ASD in offspring, incorporating either hospital or community-based diagnoses, was compared in relation to the conception method. To examine the cumulative incidence of ASD, a Kaplan-Meier survival curve was utilized. Cox proportional hazards model was employed to adjust for confounders.
RESULTS
Among 115,081 pregnancies, 0.5% involved ovulation induction (OI) and 1.7% in vitro fertilization (IVF), with the rest conceived naturally. Fertility treatments were more common in older patients and linked to more diabetes, hypertensive disorders, preterm, and cesarean deliveries. Out of 767 ASD diagnoses, offspring from OI and IVF had higher initial ASD rates (2.1% and 1.3%) than natural conceptions (0.6%). In a Cox model accounting for maternal age, ethnicity, and gender, neither OI nor IVF was significantly associated with ASD. The adjusted hazard ratios were 0.83 (95% CI 0.48-1.43) for OI and 1.34 (95% CI 0.91-1.99) for IVF. When considering fertility treatments combined, the association with ASD remained non-significant (aHR 1.11, 95% CI 0.80-1.54, p = 0.52).
CONCLUSION
Fertility treatments, including OI and IVF, do not exhibit a significant association with heightened ASD risk in offspring.
PubMed: 38926295
DOI: 10.1007/s10815-024-03180-z -
The Journal of Neuroscience : the... Jun 2024-methyl-D-aspartate receptors (NMDARs), encoded by genes, are ionotropic glutamate receptors playing a critical role in synaptic transmission, plasticity, and synapse...
-methyl-D-aspartate receptors (NMDARs), encoded by genes, are ionotropic glutamate receptors playing a critical role in synaptic transmission, plasticity, and synapse development. Genome sequence analyses have identified variants in genes in patients with neurodevelopmental disorders, but the underlying disease mechanisms are not well understood. Here, we have created and evaluated a transgenic mouse line carrying a missense variant , corresponding to a variant encoding GluN2B(L825V) found in a patient with intellectual disability (ID) and autism spectrum disorder (ASD). We used HEK293T cells expressing recombinant receptors and primary hippocampal neurons prepared from heterozygous (L825V/+) and wild-type (+/+) male and female mice to assess the functional impact of the variant. Whole-cell NMDAR currents were reduced in neurons prepared from L825V/+ compared to +/+ mice. Peak amplitude of NMDAR-mediated evoked excitatory postsynaptic currents (NMDAR-eEPSC) was not changed, but NMDAR-eEPSCs in L825V/+ neurons had faster deactivation compared to +/+ neurons and were less sensitive to a GluN2B-selective antagonist ifenprodil. Together, these results suggest a decreased functional contribution of GluN2B subunits to synaptic NMDAR currents in hippocampal neurons from L825V/+ mice. The analysis of the GluN2B(L825V) subunit surface expression and synaptic localization revealed no differences compared to wild-type GluN2B. Behavioral testing of mice of both sexes demonstrated hypoactivity, anxiety, and impaired sensorimotor gating in the L825V/+ strain, particularly affecting males, as well as cognitive symptoms. The heterozygous L825V/+ mouse offers a clinically relevant model of -related ID/ASD and our results suggest synaptic-level functional changes that may contribute to neurodevelopmental pathology. Variants in genes for subunits of N-methyl-D-aspartate receptors (NMDARs), a subtype of ionotropic glutamate receptors, are associated with neurodevelopmental disorders. Here we have generated a transgenic mouse model of a missense gene variant, identified in a patient with intellectual disability and autism, that introduces a single amino acid substitution (L825V) in the NMDAR GluN2B subunit. Di- and triheteromeric NMDARs containing the GluN2B(L825V) subunit have a reduced channel open probability. Synaptic NMDAR currents in neurons from heterozygous L825V/+ mice have accelerated deactivation and reduced ifenprodil sensitivity, suggesting synaptic loss of GluN2B function. L825V/+ mice show increased anxiety, impaired sensorimotor gating, and cognitive deficits, consistent with patient symptoms. Our study describes a clinically relevant mouse model of -related neurodevelopmental pathology.
PubMed: 38926089
DOI: 10.1523/JNEUROSCI.2291-23.2024 -
BMJ Open Jun 2024Children with atopic dermatitis (AD) are more at risk for the neurodevelopmental disorders attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder...
INTRODUCTION
Children with atopic dermatitis (AD) are more at risk for the neurodevelopmental disorders attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) with parallel increases in global prevalences. Children afflicted with these conditions appear to share similar problems in sensory modulation but investigational studies on the underlying aetiology are scarce. This scoping review aims to find knowledge gaps, collate hypotheses and to summarise available evidence on the shared pathophysiology of AD, ADHD and ASD in children.
METHODS AND ANALYSIS
Our study will follow the methodological manual published by the Joanna Briggs Methodology for Scoping Reviews and will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews. The following electronic databases will be searched for studies focused on children with AD and symptoms of ADHD and/or ASD: Medline ALL via Ovid, Embase, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials via Wiley.
ETHICS AND DISSEMINATION
This review does not require ethics approval as it will not be conducted with human participants. We will only use published data. Our dissemination strategy includes peer review publication and conference reports.
Topics: Humans; Dermatitis, Atopic; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Systematic Reviews as Topic; Child; Research Design
PubMed: 38925697
DOI: 10.1136/bmjopen-2023-081280 -
BMJ Open Jun 2024Children living in food insecure households have poorer mental health outcomes compared with their food-secure peers; however, the relationship between the severity of...
BACKGROUND
Children living in food insecure households have poorer mental health outcomes compared with their food-secure peers; however, the relationship between the severity of food insecurity and diagnosed mental health conditions in young children remains unknown. This study examined the association between household food insecurity and reported diagnosed mental health conditions among children aged 5-11 years in Canada.
METHODS
This study included 16 216 children aged 5-11 years living in Canada, from the 2019 Canadian Health Survey on Children and Youth. We measured household food insecurity using the Household Food Security Survey Module. We measured diagnosed mental health conditions by parent/caregiver report of health professional-diagnosed anxiety, depression, autism spectrum disorder or attention-deficit/hyperactive disorder. We developed a multivariable logistic regression model to assess the association between severities of food insecurity and mental health, controlling for potentially confounding variables.
RESULTS
17.0% of children lived in households reporting some level of food insecurity (5.4% marginal, 8.0% moderate and 3.6% severe). The prevalence of at least one diagnosed mental health condition in the same population was 10.9%. After adjusting for sociodemographic characteristics, children from marginal, moderate and severe food insecure households had a 1.39 (95% CI 0.99 to 1.97), 1.46 (95% CI 1.13 to 1.89) and 1.67 (95% CI 1.18 to 2.35) increased odds of having a diagnosed mental health condition, respectively.
CONCLUSION
Household food insecurity is associated with an increased presence of diagnosed mental health conditions in children aged 5-11 years. This study adds to the body of research showing that social and economic inequities, including household food insecurity, negatively impact the health of children.
Topics: Humans; Male; Female; Canada; Child, Preschool; Child; Cross-Sectional Studies; Food Insecurity; Mental Health; Logistic Models; Health Surveys; Mental Disorders; Depression; Family Characteristics; Prevalence; Anxiety; Food Supply; Autism Spectrum Disorder
PubMed: 38925691
DOI: 10.1136/bmjopen-2023-081538