Mol Autism. 2024 May 7;15(1):19. doi: 10.1186/s13229-024-00598-1.

ABSTRACT

BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance.

METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals.

RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills.

LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis.

CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.

PMID:38711098 | DOI:10.1186/s13229-024-00598-1

World Allergy Organ J. 2024 Mar 26;17(4):100888. doi: 10.1016/j.waojou.2024.100888. eCollection 2024 Apr.

ABSTRACT

BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit.

OBJECTIVE: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA.

METHODS: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders.

RESULTS: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence.

CONCLUSIONS: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

PMID:38706757 | PMC:PMC11068951 | DOI:10.1016/j.waojou.2024.100888

J Autism Dev Disord. 2024 May 6. doi: 10.1007/s10803-024-06355-w. Online ahead of print.

ABSTRACT

The current study aimed to conduct a systematic review and meta-analysis of self-management interventions for teaching daily living skills to autistic individuals. This study accessed the corresponding studies by doing a search in six databases. 14 articles and one dissertation met the inclusion criteria. The included studies were first analyzed descriptively and coded according to quality indicators using What Works Clearinghouse (WWC) standards. Second, the effect sizes of the included studies were calculated using two different effect size measures (i.e., Tau-U and performance-criteria-based effect size values [PCES]). Third, these analyses were also conducted for generalization and maintenance data. Of 15 studies included in this review, nine met the WWC standards with and without reservations. Tau-U analyses were conducted for 14 studies, whereas PCES values were calculated for only eight studies with mastery criteria. The findings indicated that the self-management interventions had a .93 CI95 (.80, 1) overall effect size for Tau-U with a very large effect. On the other hand, the overall effect size for the PCES values indicated a moderate effect with .99. The weighted effect sizes in generalization and maintenance phases were very large for Tau-U; however, moderate to high effects for PCES. Although self-management interventions showed diversity, one of the domains of daily living skills (i.e., community living skills) has not been studied in the field. Notably, among the studies in our review, the last ones are from 2019. Detailed findings from descriptive analyses and two different effect size calculations are discussed, and recommendations for future studies are given.

PMID:38709359 | DOI:10.1007/s10803-024-06355-w

J Autism Dev Disord. 2024 May 6. doi: 10.1007/s10803-024-06330-5. Online ahead of print.

ABSTRACT

Autistic girls, women and gender diverse people have specific needs that are underrepresented in research. Research priorities are often established by funding bodies, researchers, parents, carers and health professionals and may not meet the needs of the diverse Autistic community. This co-produced project aimed to identify what research would benefit the lives of Autistic girls, women and gender diverse people in Australia. We interviewed 47 Autistic girls, women and gender diverse people aged seven and above and obtained feedback from an additional 411 Autistic people through an online survey. Autistic young people identified six key research priorities including (1) better understanding and support at school, (2) understanding our experiences, strengths and challenges, (3) autism specific mental health support, (4) Autistic friendships and relationships, (5) experiences of gender diversity and (6) accommodations to make life easier for us. Eight key research priority areas were identified by Autistic adults including (1) understanding and supporting specific needs in adulthood, (2) experiences of trauma, abuse and sexual violence, (3) supporting mental health and wellbeing, (4) addressing barriers in healthcare, (5) understanding and supporting physical health needs, (6) addressing barriers in education and the workplace, (7) understanding the role of society, embracing neurodiversity and the importance of Autistic identity and (8) co-designing research and supports with Autistic people. We provide a discussion around the importance of focusing on these research priority areas in future autism research in Australia.

PMID:38709358 | DOI:10.1007/s10803-024-06330-5

J Appl Behav Anal. 2024 May 6. doi: 10.1002/jaba.1079. Online ahead of print.

ABSTRACT

We assessed whether novel praise statements could be used to (a) maintain and increase responses with existing reinforcement histories and (b) teach a previously untaught response among children diagnosed with autism spectrum disorder across two experiments. During response-stimulus pairing, two responses resulted in preferred edibles but only one also produced a praise statement. In the absence of edibles, the response continuing to produce praise tended to persist more. Next, reversing the praise contingency tended to increase the other response. However, in no case did contingent delivery of those same praise statements result in the acquisition of untaught responses. These findings suggest that conditioning praise statements could serve different functions (antecedent or consequence) depending on the reinforcement history for particular responses.

PMID:38709201 | DOI:10.1002/jaba.1079

Dev Neurorehabil. 2024 May 6:1-10. doi: 10.1080/17518423.2024.2347995. Online ahead of print.

ABSTRACT

Lack of eye contact and imitation deficits are frequently targeted in behavioral interventions for children with autism spectrum disorder (ASD). In this study, we examined the effects of prompting and modeling on the imitation skills and eye contact of three Arabic-speaking young children with ASD in Syria. A multiple baseline design with a withdrawal component was used to evaluate the effects of the intervention in a clinical setting, at a center for children with special needs, and in follow-up sessions conducted in the participants' homes. All participants' imitative responses and eye contact increased when prompting and modeling were used. Our findings support the effectiveness of prompting and modeling on imitation skills.

PMID:38709153 | DOI:10.1080/17518423.2024.2347995

Sports Med Health Sci. 2023 Nov 22;6(2):154-158. doi: 10.1016/j.smhs.2023.10.007. eCollection 2024 Jun.

ABSTRACT

Individuals with autism spectrum disorder (ASD) often exhibit motor deficits that increase their risk of falls. There is a lack of understanding regarding gait biomechanics demonstrated by older children with ASD. The purpose of the study was to determine differences in gait patterns between older children with ASD and typically developing children. Eleven children with ASD and 11 age- and gender-matched typically developing children were recruited for the study. Participants walked on a force-instrumented treadmill at a constant speed (1.1 ​m/s ​- ​1.2 ​m/s) for five minutes (min). Participants performed maximal voluntary contractions to assess their knee muscular strength. Differences between individuals with ASD and matched control participants were examined through paired t-tests with a significance level of p ​≤ ​0.05. Individuals with ASD demonstrated a smaller knee extensor torque compared to controls (p ​= ​0.002). Participants with ASD exhibited a shorter stride length (p ​= ​0.04), a greater cadence (p ​= ​0.03), and a higher variation in stride width (p ​= ​0.04) compared to control participants. The individuals with ASD experienced a greater braking ground reaction force (p ​= ​0.03) during loading response. The results indicate older children with ASD develop a unique gait pattern signified by a reduced stride length, increased cadence, and an increase of variation in stride width. This unique gait pattern may represent a movement strategy used by the individuals with ASD to compensate for the weakness associated with their knee extensor muscles. Individuals with ASD who demonstrate these unique gait deviations may face reduced postural stability and an increased risk of fall-related injuries.

PMID:38708319 | PMC:PMC11067783 | DOI:10.1016/j.smhs.2023.10.007

Campbell Syst Rev. 2024 May 3;20(2):e1405. doi: 10.1002/cl2.1405. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: Video-based interventions (VBIs) are an approach that can be used to promote social behavioural skills for autistic children and young people. Despite an abundance of literature in this area, previous evidence syntheses are limited by their exclusive search strategies and eligibility criteria. Therefore, there is a lack of comprehensive evidence syntheses to provide insight on whether these interventions work, for whom, and in what circumstances. Evidence and Gap Maps (EGMs) are used to collate vast literature on a broad topic area such as this, highlighting areas for synthesis, and identifying gaps for future research.

OBJECTIVES: To identify, map and synthesise existing primary research on VBIs promoting social behavioural skills for autistic children and young people, creating a live, searchable and publicly available EGM.

SEARCH METHODS: Searches were conducted in electronic databases (n = 8), web search engines, and other repositories including published papers and grey literature. The search strategy was developed around two concepts including (1) terms related to autism, and (2) terms related to VBIs. Searches were conducted in May 2021.

SELECTION CRITERIA: All primary studies evaluating the effectiveness of VBIs in promoting social behaviours for autistic children and young people aged 3-18 were included in the EGM.

DATA COLLECTION AND ANALYSIS: Search results were imported into Eppi-Reviewer where duplicates of identical studies were removed. Titles and abstracts were then screened by two independent reviewers. Potentially eligible full texts were located and also screened by two reviewers. Data were then extracted on study design, participant characteristics, type of intervention, type of outcome, and country of study, by one of three reviewers. EPPI-Mapper was used to create the interactive EGM.

MAIN RESULTS: The current EGM contains 438 studies reporting on 394 single subject research designs, 25 randomised controlled trials, 15 non-randomised group designs, and 8 pretest-posttest designs. Included studies evaluated VBIs in all male (n = 238), mixed gender (n = 172) or all female (n = 17) samples. VBIs employed included video modelling (n = 273), video self-modelling (n = 82), point-of-view modelling (n = 61), video prompting (n = 57), video feedback (n = 12) and computer-based video instruction (n = 4). The most frequently used models were adults (n = 191) and peers (n = 135). In relation to social outcomes, almost half evaluated social engagement (n = 199) with limited studies looking at safety (n = 9) and community (n = 7) skills.

AUTHORS' CONCLUSIONS: This EGM provides a valuable resource for policy-makers, practitioners, researchers, funders and members of the public to access evidence on VBIs promoting social behavioural skills in autistic children and young people. The map has identified areas of sufficient research where evidence can undergo synthesis. In addition, important gaps in the evidence were highlighted and suggest further research is warranted in all female samples and less frequently evaluated types of VBIs and social outcomes. Evidence included in this EGM will be further explored via systematic review and meta-analysis on control group designs.

PMID:38707947 | PMC:PMC11066762 | DOI:10.1002/cl2.1405

Methods Cell Biol. 2024;187:293-320. doi: 10.1016/bs.mcb.2024.02.033. Epub 2024 Mar 22.

ABSTRACT

Cryo-soft X-ray tomography is the unique technology that can image whole intact cells in 3D under normal and pathological conditions without labelling or fixation, at high throughput and spatial resolution. The sample preparation is relatively straightforward; requiring just fast freezing of the specimen before transfer to the microscope for imaging. It is also possible to image chemically fixed samples where necessary. The technique can be correlated with cryo fluorescence microscopy to localize fluorescent proteins to organelles within the whole cell volume. Cryo-correlated light and soft X-ray tomography is particularly useful for the study of gross morphological changes brought about by disease or drugs. For example, viral fluorescent tags can be co-localized to sites of viral replication in the soft X-ray volume. In general this approach is extremely useful in the study of complex 3D organelle structure, nanoparticle uptake or in the detection of rare events in the context of whole cell structure. The main challenge of soft X-ray tomography is that the soft X-ray illumination required for imaging has heretofore only been available at a small number of synchrotron labs worldwide. Recently, a compact device with a footprint small enough to fit in a standard laboratory setting has been deployed ("the SXT-100") and is routinely imaging cryo prepared samples addressing a variety of disease and drug research applications. The SXT-100 facilitates greater access to this powerful technique and greatly increases the scope and throughput of potential research projects. Furthermore, the availability of cryo-soft X-ray tomography in the laboratory will accelerate the development of novel correlative and multimodal workflows by integration with light and electron microscope based approaches. It also allows for co-location of this powerful imaging modality at BSL3 labs or other facilities where safety or intellectual property considerations are paramount. Here we describe the compact SXT-100 microscope along with its novel integrated cryo-fluorescence imaging capability.

PMID:38705628 | DOI:10.1016/bs.mcb.2024.02.033

Brain Res. 2024 May 3:148963. doi: 10.1016/j.brainres.2024.148963. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with two core behavioral symptoms restricted/repetitive behavior and social-communication deficit. The unknown etiology of ASD makes it difficult to identify potential treatments. Valproic acid (VPA) is an anticonvulsant drug with teratogenic effects during pregnancy in humans and rodents. Prenatal exposure to VPA induces autism-like behavior in both humans and rodents. This study aimed to investigate the protective effects of Diosgenin in prenatal Valproic acid-induced autism in rats.

METHOD: pregnant Wister female rats were given a single intraperitoneal injection of VPA (600 mg/kg, i.p.) on gestational day 12.5. The male offspring were given oral Dios (40 mg/kg, p.o.) or Carboxymethyl cellulose (5 mg/kg, p.o.) for 30 days starting from postnatal day 23. On postnatal day 52, behavioral tests were done. Additionally, biochemical assessments for oxidative stress markers were carried out on postnatal day 60. Further, histological evaluations were performed on the prefrontal tissue by Nissl staining and Immunohistofluorescence.

RESULTS: The VPA-exposed rats showed increased anxiety-like behavior in the elevated plus maze (EPM). They also demonstrated repetitive and grooming behaviors in the marble burying test (MBT) and self-grooming test. Social interaction was reduced, and they had difficulty detecting the novel object in the novel object recognition (NOR) test. Also, VPA-treated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GPX, TAC, and superoxide dismutase (SOD) levels. Furthermore, the number of neurons decreased and the ERK signaling pathway upregulated in the prefrontal cortex (PFC). On the other hand, treatment with Dios restored the behavioral consequences, lowered oxidative stress, and death of neurons, and rescued the overly activated ERK1/2 signaling in the prefrontal cortex.

CONCLUSION: Chronic treatment with Dios restored the behavioral, biochemical, and histological abnormalities caused by prenatal VPA exposure.

PMID:38705555 | DOI:10.1016/j.brainres.2024.148963

J Neurosci Methods. 2024 May 3:110157. doi: 10.1016/j.jneumeth.2024.110157. Online ahead of print.

ABSTRACT

BACKGROUND: Autism classification work on fNIRS data using dynamic graph networks. Explore the impact of the dynamic connection relationship between brain channels on ASD, and compare the brain channel connection diagrams of ASD and TD to explore potential factors that influence the development of autism.

METHOD: Using dynamic graph construction to mine the dynamic relationships of fNIRS data, obtain spatio-temporal correlations through dynamic feature extraction, and improve the information extraction capabilities of the network through spatio-temporal graph pooling to achieve classification of ASD.

RESULT: A classification effect with an accuracy of 97.2% was achieved using a short sequence of 1.75s. The results showed that the dynamic connections of channel 5 and 19, channel 12 and 25, and channel 7 and 34 have a greater impact on the classification of autism. Comparison with previously used method(s): Compared with previous deep learning models, our model achieves efficient classification using short-term fNIRS data of 1.75s, and analyzes the impact of dynamic connections on classification through dynamic graphs.

CONCLUSION: Using Dynamic Spatio-Temporal Graph Pooled Neural Networks (DSTGPN), dynamic connectivity between brain channels was found to have an impact on the classification of autism. By modelling the brain channel relationship maps of ASD and TD, hyperlink clusters were found to exist on the brain channel connections of ASD.

PMID:38705284 | DOI:10.1016/j.jneumeth.2024.110157

Sleep Med. 2024 Apr 20;119:222-228. doi: 10.1016/j.sleep.2024.04.008. Online ahead of print.

ABSTRACT

Though it is widely prescribed for improving sleep of children with autism and other neurogenetic disorders, there is a need for practical guidance to clinicians on the use of melatonin for managing insomnia in this population. Because data were either lacking or inconclusive, a task force was established by the International Pediatric Sleep Association (IPSA) to examine the literature based on clinical trials from 2012 onwards. A summary of evidence pertaining to melatonin's utility and potential side effects, practice-related caveats, and insights for use are published herewith.

PMID:38704869 | DOI:10.1016/j.sleep.2024.04.008

Mol Biol Rep. 2024 May 5;51(1):610. doi: 10.1007/s11033-024-09514-5.

ABSTRACT

Autism spectrum disorder is a neurodevelopmental condition marked by restricted interests and difficulty with social communication. ASD is characterized by heightened neuroinflammation and irregular neuronal connections. ASD is more frequent in male than female with male-female ratio of around 4:1. ASD affects 2.8% or 1 in 36 8-year-olds, based on the CDC's Morbidity and Mortality Weekly Report. Various factors like Environmental, Genetic, Epigenetic and Developmental factors are linked with genesis of ASD. Repetitive behaviors, Impaired communication skills, difficulty with social interaction are some of the clinical features of ASD. Current Pharmacotherapy of ASD limits to management of symptoms only, not cure. The stem cell therapy has a promising potential to be a breakthrough in treating ASD. Various types of stem cells have been successfully tested in children with ASD. AI has a potential to emerge as a tool for early detection of ASD. Robotics can assist the children with ASD to overcome the challenges associated with ASD.

PMID:38704762 | DOI:10.1007/s11033-024-09514-5

Mol Psychiatry. 2024 May 4. doi: 10.1038/s41380-024-02578-6. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions. Different mutations on a single ASD gene contribute to heterogeneity of disease phenotypes, possibly due to functional diversity of generated isoforms. SHANK2, a causative gene in ASD, demonstrates this phenomenon, but there is a scarcity of tools for studying endogenous SHANK2 proteins in an isoform-specific manner. Here, we report a point mutation on SHANK2, which is found in a patient with autism, located on exon of the SHANK2B transcript variant (NM_133266.5), hereby SHANK2BY29X. This mutation results in an early stop codon and an aberrant splicing event that impacts SHANK2 transcript variants distinctly. Induced pluripotent stem cells (iPSCs) carrying this mutation, from the patient or isogenic editing, fail to differentiate into functional dopamine (DA) neurons, which can be rescued by genetic correction. Available SMART-Seq single-cell data from human midbrain reveals the abundance of SHANK2B transcript in the ALDH1A1 negative DA neurons. We then show that SHANK2BY29X mutation primarily affects SHANK2B expression and ALDH1A1 negative DA neurons in vitro during early neuronal developmental stage. Mice knocked in with the identical mutation exhibit autistic-like behavior, decreased occupancy of ALDH1A1 negative DA neurons and decreased dopamine release in ventral tegmental area (VTA). Our study provides novel insights on a SHANK2 mutation derived from autism patient and highlights SHANK2B significance in ALDH1A1 negative DA neuron.

PMID:38704506 | DOI:10.1038/s41380-024-02578-6

Free Radic Biol Med. 2024 May 2:S0891-5849(24)00430-1. doi: 10.1016/j.freeradbiomed.2024.05.001. Online ahead of print.

ABSTRACT

BACKGROUND: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce.

METHODS: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9 +/- 0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied.

RESULTS: 155 of 719 (21.6%) children had ASD traits and 59 of 719 (8.2%) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 μg/L increment in selenium was 0.76 (95% CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 μg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes.

CONCLUSIONS: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

PMID:38704054 | DOI:10.1016/j.freeradbiomed.2024.05.001

Neurobiol Dis. 2024 May 2:106520. doi: 10.1016/j.nbd.2024.106520. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.

PMID:38703861 | DOI:10.1016/j.nbd.2024.106520

J Autism Dev Disord. 2024 May 4. doi: 10.1007/s10803-024-06378-3. Online ahead of print.

ABSTRACT

PURPOSE: Social experiences are consistently associated with psychological health among autistic individuals. However, most extant studies on this topic exclude individuals with autism who have lower IQ or are otherwise unable to self-report. The current study addresses this gap by examining associations of negative peer experiences and social participation with psychological health among autistic youth with low IQ.

METHODS: An online survey was collected from 268 parents of autistic adolescents and adults ages 15-25. Negative peer experiences included measures of peer victimization and being ignored. Social participation was assessed by the amount of participation and parents' perceptions of whether their youth felt the amount of participation was meeting their needs. Psychological health was assessed by parents' report of their youth's psychological quality of life, as well as whether they felt their son/daughter was currently depressed.

RESULTS: Results suggested low rates of social participation in this sample, with relatively high rates of being ignored. Regression analysis found that lower rates of peer victimization and more activities in which parents perceived that the amount of time was meeting their youth's needs was associated with higher psychological quality of life and lower likelihood that parents felt their son/daughter was depressed.

CONCLUSION: Though youth with autism and low IQ are often excluded from interventions aimed at improving social experiences, these findings suggest that promoting positive social experiences and ameliorating negative ones might be an avenue to improving psychological health in this group.

PMID:38703252 | DOI:10.1007/s10803-024-06378-3

J Autism Dev Disord. 2024 May 4. doi: 10.1007/s10803-024-06363-w. Online ahead of print.

ABSTRACT

PURPOSE: Autistic individuals often face challenges perceiving and expressing emotions, potentially stemming from differences in speech prosody. Here we explore how autism diagnoses between groups, and measures of social competence within groups may be related to, first, children's speech characteristics (both prosodic features and amount of spontaneous speech), and second, to these two factors in mothers' speech to their children.

METHODS: Autistic (n = 21) and non-autistic (n = 18) children, aged 7-12 years, participated in a Lego-building task with their mothers, while conversational speech was recorded. Mean F0, pitch range, pitch variability, and amount of spontaneous speech were calculated for each child and their mother.

RESULTS: The results indicated no differences in speech characteristics across autistic and non-autistic children, or across their mothers, suggesting that conversational context may have large effects on whether differences between autistic and non-autistic populations are found. However, variability in social competence within the group of non-autistic children (but not within autistic children) was predictive of children's mean F0, pitch range and pitch variability. The amount of spontaneous speech produced by mothers (but not their prosody) predicted their autistic children's social competence, which may suggest a heightened impact of scaffolding for mothers of autistic children.

CONCLUSION: Together, results suggest complex interactions between context, social competence, and adaptive parenting strategies in driving prosodic differences in children's speech.

PMID:38703251 | DOI:10.1007/s10803-024-06363-w

Eur J Neurosci. 2024 May 4. doi: 10.1111/ejn.16358. Online ahead of print.

ABSTRACT

Early disruptions to social communication development, including delays in joint attention and language, are among the earliest markers of autism spectrum disorder (autism, henceforth). Although social communication differences are a core feature of autism, there is marked heterogeneity in social communication-related development among infants and toddlers exhibiting autism symptoms. Neural markers of individual differences in joint attention and language abilities may provide important insight into heterogeneity in autism symptom expression during infancy and toddlerhood. This study examined patterns of spontaneous electroencephalography (EEG) activity associated with joint attention and language skills in 70 community-referred 12- to 23-month-olds with autism symptoms and elevated scores on an autism diagnostic instrument. Data-driven cluster-based permutation analyses revealed significant positive associations between relative alpha power (6-9 Hz) and concurrent response to joint attention skills, receptive language, and expressive language abilities. Exploratory analyses also revealed significant negative associations between relative alpha power and measures of core autism features (i.e., social communication difficulties and restricted/repetitive behaviors). These findings shed light on the neural mechanisms underlying typical and atypical social communication development in emerging autism and provide a foundation for future work examining neural predictors of social communication growth and markers of intervention response.

PMID:38703054 | DOI:10.1111/ejn.16358

Clin Neurophysiol. 2024 Apr 15;163:56-67. doi: 10.1016/j.clinph.2024.04.004. Online ahead of print.

ABSTRACT

OBJECTIVE: How abnormal brain signaling impacts cognition in autism spectrum disorder (ASD) remained elusive. This study aimed to investigate the local and global brain signaling in ASD indicated by theta-band functional excitation-inhibition (fE/I) ratio and explored psychophysiological relationships between fE/I, cognitive deficits, and ASD symptomatology.

METHODS: A total of 83 ASD and typically developing (TD) individuals participated in this study. Participants' interference control and set-shifting abilities were assessed. Resting-state electroencephalography (EEG) was used for estimating theta-band fE/I ratio.

RESULTS: ASD individuals (n = 31 without visual EEG abnormality; n = 22 with visual EEG abnormality) generally performed slower in a cognitive task tapping interference control and set-maintenance abilities, but only ASD individuals with visually abnormal EEG performed significantly slower than their TD counterparts (Bonferroni-corrected ps < .001). Heightened theta-band fE/I ratios at the whole-head level, left and right hemispheres were observed in the ASD subgroup without visual EEG abnormality only (Bonferroni-corrected ps < .001), which remained highly significant when only data from medication-naïve participants were analyzed. In addition, higher left hemispheric fE/I ratios in ASD individuals without visual EEG abnormality were significantly correlated with faster interference control task performance, in turn faster reaction time was significantly associated with less severe restricted, repetitive behavior (Bonferroni-corrected ps ≤ .0017).

CONCLUSIONS: Differential theta-band fE/I within the ASD population. Heightened theta-band fE/I in ASD without visual EEG abnormality may be associated with more efficient filtering of distractors and a less severe ASD symptom manifestation.

SIGNIFICANCE: Brain signaling, indicated by theta-band fE/I, was different in ASD subgroups. Only ASD with visually-normal EEG showed heightened theta-band fE/I, which was associated with faster processing of visual distractors during a cognitive task. More efficient distractor filtering was associated with less restricted, repetitive behaviors.

PMID:38703700 | DOI:10.1016/j.clinph.2024.04.004