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Autism Research : Official Journal of... Jun 2024Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and...
Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and communication. This study aims to delineate ASD subtypes based on individual gray matter brain networks and provide new insights from a graph theory perspective. In this study, we extracted and normalized single-subject gray matter networks and calculated each network's topological properties. The heterogeneity through discriminative analysis (HYDRA) method was utilized to subtype all patients based on network properties. Next, we explored the differences among ASD subtypes in terms of network properties and clinical measures. Our investigation identified three distinct ASD subtypes. In the case-control study, these subtypes exhibited significant differences, particularly in the precentral gyrus, lingual gyrus, and middle frontal gyrus. In the case analysis, significant differences in global and nodal properties were observed between any two subtypes. Clinically, subtype 1 showed lower VIQ and PIQ compared to subtype 3, but exhibited higher scores in ADOS-Communication and ADOS-Total compared to subtype 2. The results highlight the distinct brain network properties and behaviors among different subtypes of male patients with ASD, providing valuable insights into the neural mechanisms underlying ASD heterogeneity.
PubMed: 38925611
DOI: 10.1002/aur.3183 -
Toxicology Jun 2024Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like...
Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.
PubMed: 38925359
DOI: 10.1016/j.tox.2024.153871 -
General Hospital Psychiatry Jun 2024We aimed to use real-world data to characterize the burden of psychiatric comorbidities in young people with eating disorders (EDs) relative to peers without EDs.
OBJECTIVE
We aimed to use real-world data to characterize the burden of psychiatric comorbidities in young people with eating disorders (EDs) relative to peers without EDs.
METHOD
This retrospective cohort study used a large federated multi-national network of real-time electronic health records. Our cohort consisted of 124,575 people (14,524 people receiving their index, first-ever, ED diagnosis, compared to 110,051 peers without EDs initiating antidepressants). After 1:1 propensity score matching of the two cohorts by pre-existing demographic and clinical characteristics, we used multivariable logistic regression to compute the adjusted odds ratio (aOR) of psychiatric diagnoses arising in the year following the index event (either first ED diagnosis or first antidepressant script).
RESULTS
Over 50% of people with EDs had prior psychiatric diagnoses in the year preceding the index EDs diagnosis, with mood disorders, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), specific phobia (SP), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) being the most common. Adjusted analyses showed higher odds for mood disorders (aOR = 1.20 [95% CI = 1.14-1.26]), GAD (aOR = 1.28 [1.21-1.35]), PTSD (aOR = 1.29 [1.18-1.40]), and SP (aOR = 1.45 [1.31-1.60]) in the EDs cohort compared to antidepressant-initiating peers without EDs, although rates of ADHD and ASD were similar in both cohorts.
CONCLUSION
This large-scale real-time analysis of administrative data illustrates a high burden of co-occurring psychiatric disorders in people with EDs.
PubMed: 38924971
DOI: 10.1016/j.genhosppsych.2024.06.009 -
American Journal of Medical Genetics.... Jun 2024Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD),...
Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD), hypotonia, mild dysmorphic features, and multiple congenital anomalies. Joint contractures are not listed as a major feature of FOXP1-related disorder. We report five unrelated individuals, each harboring likely gene disruptive de novo FOXP1 variants or whole gene microdeletion, who showed multiple joint contractures affecting at least two proximal and/or distal joints. Consistent with the phenotype of FOXP1-related disorder, all five patients showed developmental delay with moderate-to-severe speech delay, ID, ASD, and facial dysmorphic features. FOXP1 is implicated in neuronal differentiation and in organizing motor axon projections, thus providing a potential developmental basis for the joint contractures. The combination of joint contractures and neurodevelopmental disorders supports the clinical suspicion of FOXP1-related phenotype.
PubMed: 38924631
DOI: 10.1002/ajmg.a.63713 -
The American Journal of Occupational... Jul 2024Since the first descriptions of autism, difficulties with affective contact (e.g., interpersonal exchanges of feelings between individuals) have been considered a common...
IMPORTANCE
Since the first descriptions of autism, difficulties with affective contact (e.g., interpersonal exchanges of feelings between individuals) have been considered a common feature of autism spectrum disorder, and these difficulties frequently manifest in occupational therapy interventions.
OBJECTIVE
To (1) explore how autistic young adults describe their emotions and (2) suggest ways to improve the affective contact between autistic clients and their therapists.
DESIGN
Virtual focus group interviews.
SETTING
Online (Qualtrics) survey and Zoom focus groups.
PARTICIPANTS
Autistic adults (N = 24) who met the following inclusion criteria: self-reported diagnosis of autism spectrum disorder or Asperger syndrome, age 18-35 yr, able to understand English, and able to participate in a focus group or individual interview using verbal or written communication.
RESULTS
Two themes were noted and are presented in this article: (1) Autistic people experience complex emotions and (2) autistic people's emotions are often (mis)measured and (mis)understood.
CONCLUSIONS AND RELEVANCE
The findings indicate that autistic people experience diverse, complex, and intense emotions and that these are connected to occupation. This suggests that occupational therapists must be attuned to the emotional dimension of occupation when working with autistic clients and that autistic clients may benefit from the use of embodied language to reference their emotions. Occupational therapists can help autistic clients recognize their bodily changes when experiencing emotions and to better identify and regulate their emotions. The results also show that there were many cases nonautistic people misinterpreted the emotions of autistic people on the basis of their facial expressions or words. Plain-Language Summary: This article provides information about the emotional experiences of autistic people. The study found that autistic people experience complex emotions and that those emotions are often misinterpreted or misunderstood. The author provides information on how occupational therapists can use a neurodiversity-affirming and person-centered approach to support the emotional experiences of people in the autism community. Positionality Statement: In this article, identity-first language is used when referring to autistic adults. This deliberate choice aligns with the principles of the neurodiversity-affirming movement. Autistic self-advocates have indicated a preference for this style of language over person-first language. The author would also like to acknowledge their positionality. As both a neurodivergent researcher and a self-advocate for the disabled community, this style of language aligns with their own experiences of and beliefs about their disability.
Topics: Humans; Adult; Male; Female; Young Adult; Emotions; Autism Spectrum Disorder; Occupational Therapy; Focus Groups; Adolescent; Autistic Disorder; Professional-Patient Relations; Qualitative Research
PubMed: 38923977
DOI: 10.5014/ajot.2024.050502 -
International Journal of Developmental... Jun 2024Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder...
Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)-induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real-time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction-related gene Zo-1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo-1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5-hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD-like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut-brain axis and ASD and suggest a novel therapeutic target for ASD treatment.
PubMed: 38923604
DOI: 10.1002/jdn.10354 -
Clinical Genetics Jun 2024To comprehensively investigate the neurodevelopmental profile and clinical characteristics associated with SETBP1 haploinsufficiency disorder (SETBP1-HD) and...
To comprehensively investigate the neurodevelopmental profile and clinical characteristics associated with SETBP1 haploinsufficiency disorder (SETBP1-HD) and SETBP1-related disorders (SETBP1-RD). We reported genetic results on 34 individuals, with behavior and clinical data from 22 with SETBP1-HD and 5 with SETBP1-RD, by assessing results from medical history interviews and standardized adaptive, clinical, and social measures provided from Simons Searchlight. All individuals with SETBP1-HD and SETBP1-RD exhibited neurological impairments including intellectual disability/developmental delay (IDD), attention-deficit/hyperactivity disorder, autism spectrum disorder, and/or seizures, as well as speech and language delays. While restricted interests and repetitive behaviors present challenges, a relative strength was observed in social motivation within both cohorts. Individuals with SETBP1-RD reported a risk for heart issues and compared to SETBP1-HD greater risks for orthopedic and somatic issues with greater difficulty in bowel control. Higher rates for neonatal feeding difficulties and febrile seizures were reported for individuals with SETBP1-HD. Additional prominent characteristics included sleep, vision, and gastrointestinal issues, hypotonia, and high pain tolerance. This characterization of phenotypic overlap (IDD, speech challenges, autistic, and attention deficit traits) and differentiation (somatic and heart issue risks for SETBP1-RD) between the distinct neurodevelopmental disorders SETBP1-HD and SETBP1-RD is critical for medical management and diagnosis.
PubMed: 38923504
DOI: 10.1111/cge.14579 -
Autism Research : Official Journal of... Jun 2024This study examined the differences between children and adolescents with autism spectrum disorder (ASD) and neurotypically developing (NTD) in terms of balance,...
This study examined the differences between children and adolescents with autism spectrum disorder (ASD) and neurotypically developing (NTD) in terms of balance, postural control, and motor skills. It also examined which motor skills are most affected and whether scores on different assessment tests in ASD children are correlated. A cross-sectional observational study with two research groups was conducted. Timed up and go test (TUG), short form of Bruininks-Oseretsky test of Motor Proficiency version 2 (SFBOT-2), and pediatric balance scale (PBS) were used. A total of 100 participants 50 with ASD and 50 with NTD engaged in the research. Statistically significant differences were obtained between control group and ASD group in TUG test and in SFBOT-2 standard score and total score (p-value = <0.01). A statistically significant difference (p-value = <0.01) was seen between ASD group's and control group's PBS scores. Poor correlation was noted between TUG and SFBOT-2, as well as between PBS and TUG. A moderate correlation was also found between SFBOT-2 and PBS. Children with ASD present difficulties in motor skills and in static and dynamic balance compared to children with NTD. Differences were observed in the motor skills of strength followed by manual dexterity, running speed and agility, fine motor precision, fine motor integration, and balance. The PBS item that showed the greatest difference between the ASD group and control group was maintaining monopodial support with hands on hips. Finally, poor to moderate correlations were obtained between the different tests with statistically significant differences.
PubMed: 38923217
DOI: 10.1002/aur.3181 -
International Journal of Developmental... Jun 2024Autism spectrum disorder (ASD) is a set of neurobehavioral manifestations that impose poor social interaction and stereotyped repetitive patterns. Several mircoRNA...
Autism spectrum disorder (ASD) is a set of neurobehavioral manifestations that impose poor social interaction and stereotyped repetitive patterns. Several mircoRNA (miRNA) dysregulations underpin ASD pathophysiology via impairing the neurogenic niches. For instance, miR-146a and miR-106 differential expressions are linked to deregulation of ASD-related genes and the severity of clinical symptoms, respectively. Breastfeeding provides newborns with many bioactive compounds that support their neurodevelopment including miRNA. Our pilot study evaluated the expression pattern of miR-106a and miR-146a in human milk (HM) of nursing mothers (n = 36) having autistic children compared to age-matched counterparts (n = 36) with neurotypical children as controls. Under sterile conditions, breast milk samples were collected using manual sucking pumps and centrifuged to separate the fat layer. Total RNA was extracted from the lipid fraction, and the expression profiles of both miR-106a and miR-146a were evaluated using quantitative real-time polymerase chain reaction. Among the test group, we reported some factors that were previously linked to HM miRNA perturbations: gestational diabetes, hypertension, and cesarean delivery. HM miR-106a showed comparable expression levels in both mother groups (p = 0.8681), whereas HM miR-146a was significantly downregulated in mothers with autistic children compared to controls (p = 0.0399). Alternatively, HM miR-106 levels were positively associated with two ASD clinical parameters: Childhood Autism Rating Scale (CARS) and communication and language domain of Autism Diagnostic Interview-Revised (ADI-R) (r = 0.6452, p = 0.0003 and r = 0.3958, p = 0.0410, respectively). The receiver operating characteristic (ROC) curves of both maternal HM miR-106a and miR-146a showed poor fitness as predictive biomarkers for ASD. Our findings suggest that the miR-146a differential expression in ASD children may originate at infancy during the lactation period. Thus, maternal pre- and postnatal health care is critical to maintain optimal miRNome in breast milk.
PubMed: 38922970
DOI: 10.1002/jdn.10353 -
JAMA Psychiatry Jun 2024Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is...
IMPORTANCE
Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is unknown.
OBJECTIVE
To provide unbiased population-based estimates of prevalence and risk associated with psychiatric disorders for rCNVs and to compare risks across outcomes, rCNV dosage type (deletions or duplications), and locus features.
DESIGN, SETTING, AND PARTICIPANTS
This genetic association study is an analysis of data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark in 1981-2008 and followed up until 2015, including (1) all individuals (n = 92 531) with a hospital discharge diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), or schizophrenia spectrum disorder (SSD) and (2) a subcohort (n = 50 625) randomly drawn from the source population. Data were analyzed from January 2021 to August 2023.
EXPOSURES
Carrier status of deletions and duplications at 27 autosomal rCNV loci was determined from neonatal blood samples genotyped on single-nucleotide variant microarrays.
MAIN OUTCOMES AND MEASURES
Population-based rCNV prevalence was estimated with a survey model using finite population correction to account for oversampling of cases. Hazard ratio (HR) estimates and 95% CIs for psychiatric disorders were derived using weighted Cox proportional hazard models. Risks were compared across outcomes, dosage type, and locus features using generalized estimating equation models.
RESULTS
A total of 3547 rCNVs were identified in 64 735 individuals assigned male at birth (53.8%) and 55 512 individuals assigned female at birth (46.2%) whose age at the end of follow-up ranged from 7.0 to 34.7 years (mean, 21.8 years). Most observed increases in rCNV-associated risk for ADHD, ASD, or SSD were moderate, and risk estimates were highly correlated across these disorders. Notable exceptions included high ASD-associated risk observed for Prader-Willi/Angelman syndrome duplications (HR, 20.8; 95% CI, 7.9-55). No rCNV was associated with increased MDD risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint but not with dosage type. Comparison with published case-control and community-based studies revealed a higher prevalence of deletions and lower associated increase in risk for several rCNVs in iPSYCH2015.
CONCLUSIONS AND RELEVANCE
This study found that several rCNVs were more prevalent and conferred less risk of psychiatric disorders than estimated previously. Most case-control studies overestimate rCNV-associated risk of psychiatric disorders, likely because of selection bias. In an era where genetics is increasingly being clinically applied, these results highlight the importance of population-based risk estimates for genetics-based predictions.
PubMed: 38922630
DOI: 10.1001/jamapsychiatry.2024.1453