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Assessment Jan 2024Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by challenges in social interaction and communication and the presence of restricted... (Review)
Review
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by challenges in social interaction and communication and the presence of restricted interests and repetitive behaviors. The importance of early detection of ASD and subsequent early intervention is well documented. Efforts have been made over the years to clarify ASD diagnostic criteria and develop predictive, accurate screening tools and evidence-based, standardized diagnostic instruments to aid in the identification of ASD. In this article, we review the most recent changes in ASD diagnostic criteria in the , summarize evidence-based instruments for ASD screening and diagnostic evaluations as well as the assessment of co-occurring conditions in ASD, the impact of COVID-19 on ASD assessment, and directions for future research in the field of ASD assessment.
Topics: Humans; Autism Spectrum Disorder; Diagnostic and Statistical Manual of Mental Disorders; Cognition
PubMed: 37248660
DOI: 10.1177/10731911231173089 -
Nature Sep 2023The development of the human brain involves unique processes (not observed in many other species) that can contribute to neurodevelopmental disorders. Cerebral organoids...
The development of the human brain involves unique processes (not observed in many other species) that can contribute to neurodevelopmental disorders. Cerebral organoids enable the study of neurodevelopmental disorders in a human context. We have developed the CRISPR-human organoids-single-cell RNA sequencing (CHOOSE) system, which uses verified pairs of guide RNAs, inducible CRISPR-Cas9-based genetic disruption and single-cell transcriptomics for pooled loss-of-function screening in mosaic organoids. Here we show that perturbation of 36 high-risk autism spectrum disorder genes related to transcriptional regulation uncovers their effects on cell fate determination. We find that dorsal intermediate progenitors, ventral progenitors and upper-layer excitatory neurons are among the most vulnerable cell types. We construct a developmental gene regulatory network of cerebral organoids from single-cell transcriptomes and chromatin modalities and identify autism spectrum disorder-associated and perturbation-enriched regulatory modules. Perturbing members of the BRG1/BRM-associated factor (BAF) chromatin remodelling complex leads to enrichment of ventral telencephalon progenitors. Specifically, mutating the BAF subunit ARID1B affects the fate transition of progenitors to oligodendrocyte and interneuron precursor cells, a phenotype that we confirmed in patient-specific induced pluripotent stem cell-derived organoids. Our study paves the way for high-throughput phenotypic characterization of disease susceptibility genes in organoid models with cell state, molecular pathway and gene regulatory network readouts.
Topics: Humans; Autism Spectrum Disorder; Autistic Disorder; Brain; Cell Lineage; Chromatin; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Developmental Disabilities; Gene Editing; Loss of Function Mutation; Mosaicism; Neurons; Organoids; RNA, Guide, CRISPR-Cas Systems; Single-Cell Gene Expression Analysis; Transcription, Genetic
PubMed: 37704762
DOI: 10.1038/s41586-023-06473-y -
Journal of Autism and Developmental... Aug 2023The suggested overlap between autism spectrum disorder (ASD) and gender dysphoria/incongruence (GD/GI) has been much disputed. This review showed a relationship between... (Meta-Analysis)
Meta-Analysis
The suggested overlap between autism spectrum disorder (ASD) and gender dysphoria/incongruence (GD/GI) has been much disputed. This review showed a relationship between ASD traits and GD feelings in the general population and a high prevalence of GD/GI in ASD. Our meta-analyses revealed that the pooled estimate of the prevalence of ASD diagnoses in GD/GI people was 11% (p < .001) and the overall effect size of the difference in ASD traits between GD/GI and control people was significant (g = 0.67, p < .001). Heterogeneity was high in both meta-analyses. We demonstrated that the chances that there is not a link between ASD and GD/GI are negligible, yet the size of it needs further investigation.
Topics: Humans; Gender Dysphoria; Autism Spectrum Disorder; Prevalence
PubMed: 35596023
DOI: 10.1007/s10803-022-05517-y -
Medicina Sep 2023Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently... (Review)
Review
Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroaggression crises. Serotonin reuptake inhibitors, to decrease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As specific entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism..
Topics: Humans; Autistic Disorder; Stereotyped Behavior; Anxiety; Anxiety Disorders; Autism Spectrum Disorder
PubMed: 37714122
DOI: No ID Found -
Frontiers in Cellular and Infection... 2023Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as... (Review)
Review
Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).
Topics: Humans; Autistic Disorder; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Microbiota; Gastrointestinal Microbiome; Fecal Microbiota Transplantation
PubMed: 37554355
DOI: 10.3389/fcimb.2023.1238005 -
JAMA Network Open Dec 2023Contemporary studies raise concerns regarding the implications of excessive screen time on the development of autism spectrum disorder (ASD). However, the existing... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Contemporary studies raise concerns regarding the implications of excessive screen time on the development of autism spectrum disorder (ASD). However, the existing literature consists of mixed and unquantified findings.
OBJECTIVE
To conduct a systematic review and meta-analyis of the association between screen time and ASD.
DATA SOURCES
A search was conducted in the PubMed, PsycNET, and ProQuest Dissertation & Theses Global databases for studies published up to May 1, 2023.
STUDY SELECTION
The search was conducted independently by 2 authors. Included studies comprised empirical, peer-reviewed articles or dissertations published in English with statistics from which relevant effect sizes could be calculated. Discrepancies were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Two authors independently coded all titles and abstracts, reviewed full-text articles against the inclusion and exclusion criteria, and resolved all discrepancies by consensus. Effect sizes were transformed into log odds ratios (ORs) and analyzed using a random-effects meta-analysis and mixed-effects meta-regression. Study quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Publication bias was tested via the Egger z test for funnel plot asymmetry. Data analysis was performed in June 2023.
MAIN OUTCOMES AND MEASURES
The 2 main variables of interest in this study were screen time and ASD. Screen time was defined as hours of screen use per day or per week, and ASD was defined as an ASD clinical diagnosis (yes or no) or ASD symptoms. The meta-regression considered screen type (ie, general use of screens, television, video games, computers, smartphones, and social media), age group (children vs adults or heterogenous age groups), and type of ASD measure (clinical diagnosis vs ASD symptoms).
RESULTS
Of the 4682 records identified, 46 studies with a total of 562 131 participants met the inclusion criteria. The studies were observational (5 were longitudinal and 41 were cross-sectional) and included 66 relevant effect sizes. The meta-analysis resulted in a positive summary effect size (log OR, 0.54 [95% CI, 0.34 to 0.74]). A trim-and-fill correction for a significant publication bias (Egger z = 2.15; P = .03) resulted in a substantially decreased and nonsignificant effect size (log OR, 0.22 [95% CI, -0.004 to 0.44]). The meta-regression results suggested that the positive summary effect size was only significant in studies targeting general screen use (β [SE] = 0.73 [0.34]; t58 = 2.10; P = .03). This effect size was most dominant in studies of children (log OR, 0.98 [95% CI, 0.66 to 1.29]). Interestingly, a negative summary effect size was observed in studies investigating associations between social media and ASD (log OR, -1.24 [95% CI, -1.51 to -0.96]).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that the proclaimed association between screen use and ASD is not sufficiently supported in the existing literature. Although excessive screen use may pose developmental risks, the mixed findings, the small effect sizes (especially when considering the observed publication bias), and the correlational nature of the available research require further scientific investigation. These findings also do not rule out the complementary hypothesis that children with ASD may prioritize screen activities to avoid social challenges.
Topics: Child; Adult; Humans; Autism Spectrum Disorder; Screen Time; Publication Bias
PubMed: 38064216
DOI: 10.1001/jamanetworkopen.2023.46775 -
Nutrients Aug 2023Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies,...
Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DS) or equivalent aspartame (ASP: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DS and ASP were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DS odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASP odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively ( < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DS OR = 2.7 (95% CI: 0.9, 8.4); ASP OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.
Topics: Female; Male; Pregnancy; Humans; Aspartame; Autistic Disorder; Case-Control Studies; Autism Spectrum Disorder; Retrospective Studies; Prospective Studies; Diet
PubMed: 37686804
DOI: 10.3390/nu15173772 -
Zeitschrift Fur Kinder- Und... Jul 2023Pathological Demand Avoidance: Current State of Research and Critical Discussion Pathological demand avoidance (PDA) describes children who obsessively avoid any demand... (Review)
Review
Pathological Demand Avoidance: Current State of Research and Critical Discussion Pathological demand avoidance (PDA) describes children who obsessively avoid any demand to a clinically relevant extent and is presently the subject of controversial discussion. Their behavior may be interpreted as an attempt to reduce anxiety by establishing security and predictability through rigid control of the environment as well as the demands and expectations of others. The symptoms are described in the context of autism spectrum disorder. This article reviews the current state of research and discusses the questionable validity of pathological demand avoidance as an independent diagnostic entity. It also addresses the impact of the behavior profile on development and treatment. This paper concludes that PDA is not a diagnostic entity nor a subtype of autism; rather, it is a behavior profile that can be associated with adverse illness progression and unfavorable outcomes. PDA is one feature in a complex model. We must consider not only the patient's characteristics but also those of the caregiver and their psychopathology. The reactions of the interaction partners as well as the treatment decisions play a key role play for the affected individuals. Substantial research is needed concerning the occurrence of the behavior profile PDA in diverse disorders, treatment options, and treatment responses.
Topics: Child; Humans; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Child Behavior Disorders; Anxiety; Autistic Disorder
PubMed: 36892327
DOI: 10.1024/1422-4917/a000927 -
Neuroscience and Biobehavioral Reviews Dec 2023This systematic review estimates the prevalence of co-occurring conditions (CCs) in children and adults with autism. A comprehensive search strategy consulting existing... (Meta-Analysis)
Meta-Analysis Review
This systematic review estimates the prevalence of co-occurring conditions (CCs) in children and adults with autism. A comprehensive search strategy consulting existing guidelines, diagnostic manuals, experts, carers, and autistic people was developed. PubMed and PsycInfo databases from inception to May 2022 were searched. PROSPERO registration: CRD42019132347. Two blind authors screened and extracted the data. Prevalence estimates for different CCs were summarized by using random effects models. Subgroup analyses were performed for age groups (children/adolescents vs adults) and study designs (population/registry-based vs clinical sample-based). Of 19,932 studies, 340 publications with about 590,000 participants were included and meta-analyzed to estimate the prevalence of 38-point prevalence, 27-lifetime, and 3 without distinction between point and lifetime prevalence. Point prevalence of developmental coordination disorder, sleep-wake problem, gastrointestinal problem, ADHD, anxiety disorder, overweight/obesity, feeding and eating disorder, elimination disorder, disruptive behavior, and somatic symptoms and related disorder were the most frequent CCs. Prevalence differed depending on the age group and study design. Knowing specific CCs linked to autism helps professional investigations and interventions for improved outcomes.
Topics: Child; Adolescent; Adult; Humans; Autism Spectrum Disorder; Prevalence; Obesity; Autistic Disorder; Overweight
PubMed: 37913872
DOI: 10.1016/j.neubiorev.2023.105436 -
American Journal of Human Genetics Sep 2023Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural...
Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.
Topics: Female; Pregnancy; Humans; Autism Spectrum Disorder; Pregnancy Trimester, First; Ultrasonography, Prenatal; Chromosome Mapping; Exome
PubMed: 37595579
DOI: 10.1016/j.ajhg.2023.07.010