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Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

Biomolecules. 2024 Apr 3;14(4):437. doi: 10.3390/biom14040437.

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe deficits in social communication and interaction, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid or acetaminophen, or ingestion of propionic acid, can increase the risk of ASD. Recently, epigenetic influences on ASD have come to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here, we specifically focus on the molecular influences of the abovementioned chemicals on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. We conclude that a better understanding of these phenomena can lead to more effective interventions in ASD.

PMID:38672454 | DOI:10.3390/biom14040437

Implementing an Early Detection Program for Autism Spectrum Disorders in the Polish Primary Healthcare Setting-Possible Obstacles and Experiences from Online ASD Screening

Brain Sci. 2024 Apr 16;14(4):388. doi: 10.3390/brainsci14040388.

ABSTRACT

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary healthcare. The aim of this study was to assess the opinions of parents and physicians on the legitimacy and necessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presentation of the process of online ASD screening, which was part of the validation program for the Polish version of one of the screening tools. This study involved 418 parents whose children were screened online and 95 primary care physicians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in the general population without a clear preference as to the screening method (online or in person). Moreover, online screening is considered by respondents as a satisfactory diagnostic method. Therefore, online screening may prove to be at least a partial method of solving numerous obstacles indicated by participants' systemic difficulties including time constraints, the lack of experienced specialists in the field of developmental disorders and organizational difficulties of healthcare systems.

PMID:38672037 | DOI:10.3390/brainsci14040388

Prevalence and Correlates of the Concurrence of Autism Spectrum Disorder and Obsessive Compulsive Disorder in Children and Adolescents: A Systematic Review and Meta-Analysis

Brain Sci. 2024 Apr 13;14(4):379. doi: 10.3390/brainsci14040379.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two common and impairing neurodevelopmental conditions with partial symptomatic overlap. The aim of this study is to systematically and meta-analytically examine the following: (i) the prevalence of an OCD diagnosis among young people with ASD, (ii) the prevalence of an ASD diagnosis among young people with OCD, and (iii) the clinical and therapeutic implications of such comorbidity.

METHOD: A multistep literature search was performed from database inception until 17 November 2023. This PRISMA/MOOSE-compliant systematic review, registered in PROSPERO (CRD42023480543), identified studies reporting on the prevalence, sociodemographic, psychopathologic, prognostic, and therapeutic correlates of OCD and ASD concurrence in children and adolescents. A quantitative meta-analysis with random effects was conducted to analyse the pooled prevalence of OCD among samples with a mean age of < 18 years old with ASD and the prevalence of ASD among individuals under 18 with OCD. Sensitivity analyses were performed to investigate the effect of diagnostic criteria and different continents. Meta-regression analyses were conducted to examine the effect of gender, age, IQ, and OCD severity scores. A narrative review of the clinical and therapeutical implications of the comorbidity was provided.

RESULTS: 42 studies were selected for the systematic review (SR), and 31 of them were also included in one of the meta-analyses. The pooled prevalence of OCD among ASD youth samples (n = 8916, mean age = 10.6 ± 1.6; 16.4% female) was 11.6% (95% confidence intervals [CI] = 6.9%; 18.8%), and the pooled prevalence of ASD among OCD children and adolescent samples (n = 6209, mean age = 14.1 ± 1.4; 45.7% female) was 9.5% (95% CI = 6.0%; 14.7%). Meta-regressions found a statistically higher prevalence of ASD among samples with a lower prevalence of females (β = -4.7; 95%CI = -8.6; -0.8). Children with both OCD and ASD present higher rates of functional impairment, psychopathology, and other comorbidities, compared to youth with either of the disorders alone.

CONCLUSIONS: OCD and ASD are highly concurrent conditions in youth, with symptomatic, prognostic, severity, and therapeutic implications. Future research should focus on conducting longitudinal cohort studies prospectively to determine development trajectories, along with randomized controlled trials to assess the efficacy of specific therapeutic interventions.

PMID:38672028 | DOI:10.3390/brainsci14040379

Behavioral and Psychiatric Disorders in Syndromic Autism

Brain Sci. 2024 Mar 30;14(4):343. doi: 10.3390/brainsci14040343.

ABSTRACT

Syndromic autism refers to autism spectrum disorder diagnosed in the context of a known genetic syndrome. The specific manifestations of any one of these syndromic autisms are related to a clinically defined genetic syndrome that can be traced to certain genes and variants, genetic deletions, or duplications at the chromosome level. The genetic mutations or defects in single genes associated with these genetic disorders result in a significant elevation of risk for developing autism relative to the general population and are related to recurrence with inheritance patterns. Additionally, these syndromes are associated with typical behavioral characteristics or phenotypes as well as an increased risk for specific behavioral or psychiatric disorders and clinical findings. Knowledge of these associations helps guide clinicians in identifying potentially treatable conditions that can help to improve the lives of affected patients and their families.

PMID:38671997 | DOI:10.3390/brainsci14040343

Examining Language, Speech and Behaviour Characteristics: A Cross-Sectional Study in Saudi Arabia Using the Arabic Version of Gilliam Autism Rating Scale-Third Edition

Children (Basel). 2024 Apr 15;11(4):472. doi: 10.3390/children11040472.

ABSTRACT

Autism spectrum disorder (ASD) exhibits diverse manifestations influenced by demographic factors. This study evaluates these variations within Saudi Arabia, aiming to investigate language, speech and behaviour characteristics across different demographics in Saudi Arabia using the Arabic Version of the Gilliam Autism Rating Scale-Third Edition (A-GARS-3). Employing a cross-sectional design, 178 participants were stratified by developmental status (n = 124 school settings, n = 54 clinical setting), sex (Females = 77, Males =101), age (range = 3-22), and geographical region (different provinces in Saudi Arabia). The A-GARS-3 measured ASD manifestations across six subscales. The study identified significant differences in ASD manifestations by developmental status, with higher ASD likelihood and severity in clinical settings. Younger children showed more pronounced ASD characteristics, and males were slightly more likely to be diagnosed with ASD. Geographical analysis revealed regional differences in severity. The findings underline the importance of demographic considerations in ASD assessment and diagnosis, suggesting the need for age-specific and culturally sensitive approaches. The A-GARS-3 is a reliable tool for the Saudi context. Regional disparities in ASD prevalence and severity indicate a need for tailored health policies and resources across Saudi provinces.

PMID:38671690 | DOI:10.3390/children11040472

Comparing Executive Functions in Children and Adolescents with Autism and ADHD-A Systematic Review and Meta-Analysis

Children (Basel). 2024 Apr 15;11(4):473. doi: 10.3390/children11040473.

ABSTRACT

Two neurodevelopmental conditions, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), have been associated with executive function (EF) impairments but the specificity of their impairments is still controversial. The present meta-analysis aimed to identify the differences in EF profiles of ASD, ADHD, and ASD+ADHD in relation to a control group of individuals with typical development (TD) and to understand whether the EF performance could change depending upon the type of measure used to assess EF (performance tests vs. questionnaires). Results from 36 eligible studies revealed that ADHD and ASD showed more difficulties than the TD group in tests and, particularly, in questionnaires. No significant differences in the EF profile emerged between ASD and ADHD when assessed through neuropsychological tests (d = 0.02), while significant differences emerged when assessed through questionnaires, with ADHD having higher ratings than ASD (d = -0.34). EF questionnaires and neuropsychological tests may catch two different constructs of EF, with the former being more predictive of everyday life EF impairments. The comparison between the double diagnosis group (ADHD+ASD) and the clinical groups pointed out that the former has a more similar EF profile to the ADHD-alone one and that it shows more difficulties than ASD-alone.

PMID:38671689 | DOI:10.3390/children11040473

A Pilot Study Exploring Caregivers' Experiences Related to the Use of a Smart Toothbrush by Children with Autism Spectrum Disorder

Children (Basel). 2024 Apr 11;11(4):460. doi: 10.3390/children11040460.

ABSTRACT

BACKGROUND: Research on caregivers for children with intellectual disabilities, particularly those with autism spectrum disorder (ASD), has highlighted several obstacles to achieving better oral health. These include challenges with tolerating oral care, sensory processing differences, uncooperative behaviors, and communication impairments. There is limited understanding of what caregivers would consider "successful assistance" in improving oral health for these children.

OBJECTIVES: This pilot study aimed to examine caregivers' and user's experiences with a Kids Smart Electric Toothbrush used by children with ASD.

METHODS: It involved open-ended interviews and questionnaires with caregivers prior to utilization of the toothbrush and after 4 weeks of product use by the child.

RESULTS: Seventeen children with ASD, aged 5-12, participated. A total of 58.8% of caregivers said their child brushed more often, and all reported brushing at least twice a day by week 4. Caregivers reported that children became more independent while brushing their teeth and achieved better quality brushing. Caregivers' frustration with the brushing process, satisfaction with the device, and need to assist the child with brushing were improved. Caregivers did encounter some technical difficulties with the app.

CONCLUSION: This study will assist in exploring "smart" toothbrush technologies for oral hygiene in children with ASD.

PMID:38671677 | DOI:10.3390/children11040460

A Prediction Model of Autism Spectrum Diagnosis from Well-Baby Electronic Data Using Machine Learning

Children (Basel). 2024 Apr 3;11(4):429. doi: 10.3390/children11040429.

ABSTRACT

Early detection of autism spectrum disorder (ASD) is crucial for timely intervention, yet diagnosis typically occurs after age three. This study aimed to develop a machine learning model to predict ASD diagnosis using infants' electronic health records obtained through a national screening program and evaluate its accuracy. A retrospective cohort study analyzed health records of 780,610 children, including 1163 with ASD diagnoses. Data encompassed birth parameters, growth metrics, developmental milestones, and familial and post-natal variables from routine wellness visits within the first two years. Using a gradient boosting model with 3-fold cross-validation, 100 parameters predicted ASD diagnosis with an average area under the ROC curve of 0.86 (SD < 0.002). Feature importance was quantified using the Shapley Additive explanation tool. The model identified a high-risk group with a 4.3-fold higher ASD incidence (0.006) compared to the cohort (0.001). Key predictors included failing six milestones in language, social, and fine motor domains during the second year, male gender, parental developmental concerns, non-nursing, older maternal age, lower gestational age, and atypical growth percentiles. Machine learning algorithms capitalizing on preventative care electronic health records can facilitate ASD screening considering complex relations between familial and birth factors, post-natal growth, developmental parameters, and parent concern.

PMID:38671647 | DOI:10.3390/children11040429

Real-time coded measures in natural language samples capture change over time in minimally verbal autistic children

Autism Res. 2024 Apr 26. doi: 10.1002/aur.3142. Online ahead of print.

ABSTRACT

Prior research supports the use of natural language sampling (NLS) to assess the rate of speech utterances (URate) and the rate of conversational turns (CTRate) in minimally verbal (MV) autistic children. Bypassing time-consuming transcription, previous work demonstrated the ability to derive URate and CTRate using real-time coding methods and provided support for their strong psychometric properties. (1) Unexplored is how URate and CTRate using real-time coding methods capture change over time and (2) whether specific child factors predict changes in URate and CTRate in 50 MV autistic children (40 males; M = 75.54, SD = 16.45 (age in months)). A NLS was collected at Time 1 (T1) and Time 2 (T2) (4.5 months between T1 and T2) and coding was conducted in ELAN Linguistic Annotator software using a real-time coding approach to derive URate and CTRate. Findings from paired samples Wilcoxon tests revealed a significant increase in child URate (not examiner URate) and child and examiner CTRate from T1 to T2. Child chronological age, Mullen expressive language age equivalent scores, and URate and CTRate at T1 were predictive of URate and CTRate at T2. Findings support using NLS-derived real-time coded measures of URate and CTRate to efficiently capture change over time in MV autistic children. Identifying child factors that predict changes in URate and CTRate can help in the tailoring of goals to children's individual needs and strengths.

PMID:38670930 | DOI:10.1002/aur.3142

Parent-Led Cognitive Behavioral Teletherapy for Anxiety in Autistic Youth: A Randomized Trial Comparing Two Levels of Therapist Support

Behav Ther. 2024 May;55(3):499-512. doi: 10.1016/j.beth.2023.08.008. Epub 2023 Sep 6.

ABSTRACT

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders, though to date it has been minimally tested. In this study, 87 autistic youth (7 to 13 years old) with anxiety disorders and their parents were randomized to two forms of parent-led CBT in which parents led their child through a guided CBT workbook across 12 weeks: one with low therapist contact (four 30-minute telehealth calls), and one with standard therapist contact (ten 60-minute telehealth calls). Anxiety, functional impairment, and autism features significantly declined across therapy, without differences between groups. High satisfaction was reported in both groups, though significantly higher satisfaction ratings were reported in standard-contact CBT. Responder rates were 69% of completers at posttreatment (70% in standard contact, 68% in low contact) and 86% at 3-month follow-up (86% in standard contact, 87% in low contact). Low-contact CBT was estimated to incur an average cost of $755.70 per family compared with $1,978.34 in standard-contact CBT. Parent-led CBT with minimal or standard therapist contact both appear to be effective CBT delivery formats for autistic youth with anxiety disorders, with significant cost savings for low-contact CBT.

PMID:38670664 | DOI:10.1016/j.beth.2023.08.008

Follow-up of telehealth parent training for sleep disturbances in young children with autism spectrum disorder

Sleep Med. 2024 Apr 23;119:114-117. doi: 10.1016/j.sleep.2024.04.022. Online ahead of print.

ABSTRACT

OBJECTIVE/BACKGROUND: Bedtime and sleep disturbances are ubiquitous in children with autism. The telehealth delivery of a behavior analytic parent training program was earlier reported to be efficacious in improving child sleep and parent sense of competency. Our aim in this brief report was to determine the durability of the telehealth delivered sleep parent training program (SPT) compared to the control condition in this randomized controlled trial. Telehealth delivery could be a means to expand access to such early treatment if efficacious.

PARTICIPANTS/METHODS: Parents of young children, ages 2-7 years, with autism and co-occurring sleep disturbances were enrolled in this study. Participants were randomized to either SPT or a comparison arm that included non-sleep related parent education except for one session Sleep Parent Education; SPE). Each participant was individually administered a 5 session program delivered over 10 weeks. Outcome measures were collected at weeks 5 and 10 and at post-treatment follow-up at 16 weeks.

RESULTS: Follow-up week 16 data were available for 30 participants randomized to SPT and 24 participants randomized to SPE. Demographics for this follow-up cohort were similar to the full sample. At week 16 follow-up, there was a significant group difference between SPT and SPE the Modified Simonds & Parraga Sleep Questionnaire-Composite Sleep Index (MSPSQ - CSI) (p = 0.011) with an effect size of 0.68. Further, 8 of the 10 children in SPT who were negative responders at the week 10 endpoint were rated as positive responders at week 16 by the treatment masked IE compared to 2 out of 12 in the SPE group (p = 0.008).

CONCLUSIONS: Post-treatment follow-up data suggests SPT is durable over time compared to SPE, the active control group. Further, for some participants in SPT, a positive responsive emerged after the treatment endpoint. This brief report adds to the efficacy of SPT as a time-limited intervention for insomnia in young autistic children.

PMID:38669834 | DOI:10.1016/j.sleep.2024.04.022

Autistic Women's Experience of Motherhood: A Qualitative Analysis of Reddit

J Autism Dev Disord. 2024 Apr 26. doi: 10.1007/s10803-024-06312-7. Online ahead of print.

ABSTRACT

Autistic mothers remain under-represented in parental and autism research despite the associated physical and psychosocial challenges that accompany the transition to motherhood. Extant literature suggests autistic mothers experience sensory difficulties, communication challenges, stigma, and comorbidities as difficulties, but these studies have focused on autistic women in the perinatal period. The aim of this study was to examine reflections on motherhood from a Reddit community for autistic parents. Identified themes were Autistic Mothering is Different, Autistic Mothers Need Autistic Mothers, Autistic Mothers Experience Stigma, and Learnings from Lockdown. Findings extend existing research by offering insight into the ways autism impacts mothers beyond the perinatal period and have important implications for the future design and delivery of support services for autistic mothers.

PMID:38668893 | DOI:10.1007/s10803-024-06312-7

Effects of Physical Activity on Cognition, Behavior, and Motor Skills in Youth with Autism Spectrum Disorder: A Systematic Review of Intervention Studies

Behav Sci (Basel). 2024 Apr 15;14(4):330. doi: 10.3390/bs14040330.

ABSTRACT

The aim of this paper was to analyze the acute and chronic effects of physical activity (PA) on cognition, behavior, and motor skill in youth with autism spectrum disorder (ASD), taking into account potential confounders. In addition, it was intended to elaborate a guide of educational applications with strategies for PA use. Studies were identified in four databases from January 2010 to June 2023. A total of 19 interventional studies met the inclusion criteria. PA programs ranged from two weeks to one year in duration, with a frequency of one to five sessions per week. More than 58% of the studies showed positive effects of PA on cognition, and 45.5% on behavior and motor skill. Moderate-vigorous PA for 15-30 min has shown acute effects on cognition, general behavior, and stereotypic/repetitive behaviors in youth with ASD. A total of 9 out of 14 studies showed chronic effects on general behavior and stereotypic behaviors, and only 6 on motor skills.

PMID:38667126 | DOI:10.3390/bs14040330

Autism Spectrum Disorder- and/or Intellectual Disability-Associated Semaphorin-5A Exploits the Mechanism by Which Dock5 Signalosome Molecules Control Cell Shape

Curr Issues Mol Biol. 2024 Apr 2;46(4):3092-3107. doi: 10.3390/cimb46040194.

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger's syndrome, and pervasive developmental disorder. Individuals with ASD may exhibit difficulties in social interactions, communication challenges, repetitive behaviors, and restricted interests. While genetic mutations in individuals with ASD can either activate or inactivate the activities of the gene product, impacting neuronal morphogenesis and causing symptoms, the underlying mechanism remains to be fully established. Herein, for the first time, we report that genetically conserved Rac1 guanine-nucleotide exchange factor (GEF) Dock5 signalosome molecules control process elongation in the N1E-115 cell line, a model line capable of achieving neuronal morphological changes. The increased elongation phenotypes observed in ASD and intellectual disability (ID)-associated Semaphorin-5A (Sema5A) Arg676-to-Cys [p.R676C] were also mediated by Dock5 signalosome molecules. Indeed, knockdown of Dock5 using clustered regularly interspaced short palindromic repeat (CRISPR)/CasRx-based guide(g)RNA specifically recovered the mutated Sema5A-induced increase in process elongation in cells. Knockdown of Elmo2, an adaptor molecule of Dock5, also exhibited similar recovery. Comparable results were obtained when transfecting the interaction region of Dock5 with Elmo2. The activation of c-Jun N-terminal kinase (JNK), one of the primary signal transduction molecules underlying process elongation, was ameliorated by either their knockdown or transfection. These results suggest that the Dock5 signalosome comprises abnormal signaling involved in the process elongation induced by ASD- and ID-associated Sema5A. These molecules could be added to the list of potential therapeutic target molecules for abnormal neuronal morphogenesis in ASD at the molecular and cellular levels.

PMID:38666924 | DOI:10.3390/cimb46040194

Probiotics in autism spectrum disorder: Recent insights from animal models

Autism. 2024 Apr 26:13623613241246911. doi: 10.1177/13623613241246911. Online ahead of print.

ABSTRACT

Autism spectrum disorder is a neurodevelopmental disorder characterized by a wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism spectrum disorder, often proving ineffective and accompanied by a multitude of side effects. The gut microbiota is the reservoir of bacteria inhabiting our gastrointestinal tract. The gut microbial alterations observed in individuals with autism spectrum disorder, including elevated levels of Bacteroidetes, Firmicutes, and Proteobacteria, as well as reduced levels of Bifidobacterium, provide a basis for further investigation into the role of the gut microbiota in autism spectrum disorder. Recent preclinical studies have shown favorable outcomes with probiotic therapy, including improvements in oxidative stress, anti-inflammatory effects, regulation of neurotransmitters, and restoration of microbial balance. The aim of this review is to explore the potential of probiotics for the management and treatment of autism spectrum disorder, by investigating insights from recent studies in animals.

PMID:38666595 | DOI:10.1177/13623613241246911

Mothering and mother-child interactions in the unaffected siblings of autistic children

Dev Med Child Neurol. 2024 Apr 26. doi: 10.1111/dmcn.15917. Online ahead of print.

ABSTRACT

AIM: To investigate parenting and mother-child interactions in unaffected siblings of autistic children.

METHOD: This cross-sectional study enrolled 274 probands with a DSM-5 diagnosis of autism spectrum disorder (ASD) (87.4% male; mean [SD] age = 11 years 4 months [3 years 2 months]), their unaffected siblings (n = 274, 46.72% male; mean [SD] age = 11 years 3 months [3 years 4 months]), and 296 age-balanced and sex-balanced typically developing children (82.77% male; mean [SD] age = 11 years 3 months [2 years 8 months]). Maternal parenting styles and mother-child interactions were assessed using maternal reporting.

RESULTS: Regardless of the child's age, maternal educational level, or presence of attention-deficit/hyperactivity disorder, autistic children received more overprotective and controlling parental behaviour than unaffected children. Correlates for parenting, mother-child interactions, and behavioural problems in the home setting in children with ASD and typically developing children were autistic traits, maternal anxiety and depressive symptoms, and maternal autistic characteristics; those in unaffected siblings were age, autistic traits, maternal educational level, and maternal autistic characteristics.

INTERPRETATION: The diagnosis of ASD in a child can significantly influence maternal parenting behaviours, mother-child interactions, and the child's behavioural problems in the home setting. Furthermore, maternal anxiety or depressive symptoms, along with autistic characteristics in both mother and child, might shape parenting practices and exacerbate behavioural difficulties in autistic children.

PMID:38666483 | DOI:10.1111/dmcn.15917

A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood

Psychoradiology. 2023 Apr 20;3:kkad005. doi: 10.1093/psyrad/kkad005. eCollection 2023.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers, particularly in young children at the age when symptoms become fully established. Furthermore, such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level.

OBJECTIVE: This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children.

METHODS: A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) together with symptom severity and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets.

RESULTS: Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification achieved very high accuracy of 96.77% in the discovery dataset, and 91.67% and 88.89% in the two independent validation datasets.

CONCLUSIONS: Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

PMID:38666122 | PMC:PMC11003421 | DOI:10.1093/psyrad/kkad005

Connectome-based prediction of the severity of autism spectrum disorder

Psychoradiology. 2023 Nov 27;3:kkad027. doi: 10.1093/psyrad/kkad027. eCollection 2023.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is characterized by social and behavioural deficits. Current diagnosis relies on behavioural criteria, but machine learning, particularly connectome-based predictive modelling (CPM), offers the potential to uncover neural biomarkers for ASD.

OBJECTIVE: This study aims to predict the severity of ASD traits using CPM and explores differences among ASD subtypes, seeking to enhance diagnosis and understanding of ASD.

METHODS: Resting-state functional magnetic resonance imaging data from 151 ASD patients were used in the model. CPM with leave-one-out cross-validation was conducted to identify intrinsic neural networks that predict Autism Diagnostic Observation Schedule (ADOS) scores. After the model was constructed, it was applied to independent samples to test its replicability (172 ASD patients) and specificity (36 healthy control participants). Furthermore, we examined the predictive model across different aspects of ASD and in subtypes of ASD to understand the potential mechanisms underlying the results.

RESULTS: The CPM successfully identified negative networks that significantly predicted ADOS total scores [r (df = 150) = 0.19, P = 0.008 in all patients; r (df = 104) = 0.20, P = 0.040 in classic autism] and communication scores [r (df = 150) = 0.22, P = 0.010 in all patients; r (df = 104) = 0.21, P = 0.020 in classic autism]. These results were reproducible across independent databases. The networks were characterized by enhanced inter- and intranetwork connectivity associated with the occipital network (OCC), and the sensorimotor network (SMN) also played important roles.

CONCLUSIONS: A CPM based on whole-brain resting-state functional connectivity can predicted the severity of ASD. Large-scale networks, including the OCC and SMN, played important roles in the predictive model. These findings may provide new directions for the diagnosis and intervention of ASD, and maybe could be the targets in novel interventions.

PMID:38666105 | PMC:PMC10917386 | DOI:10.1093/psyrad/kkad027

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