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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 -
Biology May 2024Exosomes are 30-150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs... (Review)
Review
Exosomes are 30-150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs (mRNAs, microRNAs/miRNAs, long non-coding RNAs/lncRNAs), and DNA of their parent cell. In pathological conditions, the composition of exosomes is altered, making exosomes a potential source of biomarkers for disease diagnosis. Exosomes can cross the blood-brain barrier (BBB), which is an advantage for using exosomes in the diagnosis of central nervous system (CNS) diseases. Neuropsychiatric diseases belong to the CNS diseases, and many potential diagnostic markers have been identified for neuropsychiatric diseases. Here, we review the potential diagnostic markers of exosomes in neuropsychiatric diseases and discuss the potential application of exosomal biomarkers in the early and accurate diagnosis of these diseases. Additionally, we outline the limitations and future directions of exosomes in the diagnosis of neuropsychiatric diseases.
PubMed: 38927267
DOI: 10.3390/biology13060387 -
BMC Biology Jun 2024The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans....
BACKGROUND
The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans. Patients with mutations in VPS50 show severe developmental delay and intellectual disability, characteristics that have been associated with autism spectrum disorders (ASDs). The mechanisms that link VPS50 mutations to ASD are unknown.
RESULTS
To examine the role of VPS50 in mammalian brain function and behavior, we used the CRISPR/Cas9 system to generate knockouts of VPS50 in both cultured murine cortical neurons and living mice. In cultured neurons, KO of VPS50 did not affect the number of synaptic vesicles but did cause mislocalization of the V-ATPase V1 domain pump and impaired synaptic activity, likely as a consequence of defects in vesicle acidification and vesicle content. In mice, mosaic KO of VPS50 in the hippocampus altered synaptic transmission and plasticity and generated robust cognitive impairments.
CONCLUSIONS
We propose that VPS50 functions as an accessory protein to aid the recruitment of the V-ATPase V1 domain to synaptic vesicles and in that way plays a crucial role in controlling synaptic vesicle acidification. Understanding the mechanisms controlling behaviors and synaptic function in ASD-associated mutations is pivotal for the development of targeted interventions, which may open new avenues for therapeutic strategies aimed at ASD and related conditions.
Topics: Animals; Mice; Mice, Knockout; Synaptic Vesicles; Vacuolar Proton-Translocating ATPases; Synaptic Transmission; Brain; Behavior, Animal; Synapses; Neurons; Vesicular Transport Proteins
PubMed: 38926759
DOI: 10.1186/s12915-024-01940-y -
Trials Jun 2024Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts...
Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial.
INTRODUCTION
Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called "Adappt," aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences.
METHOD
A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with "Adappt."
DISCUSSION
Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care.
TRIAL REGISTRATION
This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).
Topics: Humans; Mindfulness; Parents; Mental Health; Neurodevelopmental Disorders; Child; Pragmatic Clinical Trials as Topic; Multicenter Studies as Topic; Mobile Applications; Psychology, Positive; Adolescent; Stress, Psychological; Treatment Outcome; Adaptation, Psychological; Randomized Controlled Trials as Topic
PubMed: 38926739
DOI: 10.1186/s13063-024-08256-w -
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 -
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 -
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