Comorbid Autism Spectrum Disorder Research Articles

Prevalence of comorbidity of autism and ADHD and associated characteristics in school population: EPINED study.

Autism and attention deficit hyperactivity disorder (ADHD) comorbidity in the school population have been understudied. This study estimates its prevalence considering both parents' and teachers' reports and clinical diagnosis. Sociodemographic, clinical, and cognitive data were compared by diagnostic groups: autism, ADHD, autism and ADHD, subthreshold autism spectrum disorder (ASD), subthreshold ADHD, and children without neurodevelopmental conditions. Following a two-phase design, 3727 parents and teachers (1802 preschoolers, 1925 school-age children) participated in the first phase. Subsequently, 781 participants underwent individual assessment for DSM-5 diagnoses. The estimated prevalence of the comorbid diagnosis was 0.51% (0.28%-0.74%), with significant sex differences (0.16% girls, 0.89% boys). The cooccurrence of symptoms of autism and ADHD reported by parents or teachers was 3.2% and 2.6%, respectively. ADHD comorbidity was observed in 32.8% of autistic children and 31.4% of those with subthreshold ASD. ASD comorbidity was observed in 9.8% of children with ADHD and 5.7% of those with subthreshold ADHD. Comorbidity was reported by at least one informant in 95% of children. Only 15.8% of children with autism and ADHD had been previously diagnosed with both conditions. Early detection and accurate comorbidity diagnosis are crucial to address the clinical and socio-educational needs of these children.

Associations of meeting 24-hour movement behavior guidelines with social and emotional function in youth with ASD/ADHD

BackgroundThe 24-hour movement behavior (24-HMB) guidelines recommend that children and adolescents should limit screen time (ST), get an adequate amount of sleep (SL), and engage in sufficient physical activity (PA) to ensure health and healthy development. Meeting 24-HMB guidelines is associated with positive mental health outcomes (e.g., social and emotional function) in the general population. However, it is unclear whether such findings extend to children and adolescents with comorbid Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). Thus, we examined associations of meeting 24-HMB guidelines with social and emotional function in children and adolescents with comorbid ASD/ADHD. MethodsData from the 2020–2021 National Survey of Children's Health - a U.S. national, population-based, cross-sectional study – were used. We extracted and analyzed data on children and adolescents (aged between 6 and 17 years) diagnosed with comorbidity of ASD/ADHD. Data on movement behaviors (PA, ST, and SL) and specific outcome variables (social function and emotional function) were collected through caregiver-proxy reports. Logistic regressions were performed to examine the associations between meeting 24-HMB guidelines and social and emotional outcomes adjusting for covariates (e.g., age, sex, ethnicity, weight status, birth status, socio-economic status, and receiving medication/behavioral treatment). ResultsAmong 979 children and adolescents with comorbid ASD/ADHD, only 3.8 % met all three 24-HMB guidelines. In total, 45.0 % of participants met at least one guideline, and 25.5 % of those met at least two guidelines. Compared to those who did not meet any 24-HMB guidelines, meeting SL + ST guidelines was significantly associated with lower odds of poorer social function (being bullied: OR = 0.3, 95%CI [0.1–0.7]; arguing: OR = 0.2, 95%CI[0.1–0.4]). Furthermore, meeting PA + ST + SL guidelines was associated with lower odds of poorer emotional function (depression: OR = 0.5, 95%CI[0.3–0.7]). ConclusionMeeting 24-HMB guidelines was associated with better social and emotional function in U.S. children and adolescents with comorbid ASD/ADHD; however, currently very few with comorbid ASD/ADHD meet all 24-HMB guidelines. These results emphasize the importance of promoting adherence to the 24-HMB guidelines among children and adolescents facing the challenges of comorbid ASD/ADHD. These cross-sectional findings point to the need for further empirical evidence from longitudinal studies to support our conclusions.

A novel framework for functional annotation of variants of uncertain significance in ID/ASD risk gene CC2D1A.

Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous with hundreds of identified risk genes, most affecting only a few patients. Novel missense variants in these genes are being discovered as clinical exome sequencing is now routinely integrated into diagnosis, yet most of them are annotated as variants of uncertain significance (VUS). VUSs are a major roadblock in using patient genetics to inform clinical action. We developed a framework to characterize VUSs in Coiled-coil and C2 domain containing 1A (CC2D1A), a gene causing autosomal recessive ID with comorbid ASD in 40% of cases. We analyzed seven VUSs (p.Pro319Leu, p.Ser327Leu, p.Gly441Val, p.Val449Met, p.Thr580Ile, p.Arg886His and p.Glu910Lys) from four cases of individuals with ID and ASD. Variants were cloned and overexpressed in HEK293 individually and in their respective heterozygous combination. CC2D1A is a signaling scaffold that positively regulates PKA-CREB signaling by repressing phosphodiesterase 4D (PDE4D) to prevent cAMP degradation. After testing multiple parameters including direct interaction between PDE4D and CC2D1A, cAMP levels and CREB activation, we found that the most sensitive readout was CREB transcriptional activity using a luciferase assay. Compared to WT CC2D1A, five VUSs (p.Pro319Leu, p.Gly441Val, p.Val449Met, p.Thr580Ile, and p.Arg886His) led to significantly blunted response to forskolin induced CREB activation. This luciferase assay approach can be scaled up to annotate ~150 CC2D1A VUSs that are currently listed in ClinVar. Since CREB activation is a common denominator for multiple ASD/ID genes, our paradigm can also be adapted for their VUSs.

Characteristics and Co-morbidities of Autism Spectrum Disorder as Predictors of Severity: A National Survey in the United States (P1-8.006)

Characteristics and Co-morbidities of Autism Spectrum Disorder as Predictors of Severity: A National Survey in the United States (P1-8.006)

Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors

Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-Δexon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism. CBD rescued the cognitive deficits displayed by juvenile Fmr1-Δexon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-Δexon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH. These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.

Personalized repetitive transcranial magnetic stimulation guided by the spectral electroencephalogram may enhance and democratize therapy for autism spectrum disorder

Autism spectrum disorder (ASD) is a genetically heterogeneous group of neurodevelopmental disorders that affect 1 in 36 children (CDC data) and have recognizable core deficits in common, including repetitive stereotyped behaviors and difficulties in social interaction and communication. Pharmacological interventions moderate some ASD comorbidities, but do not alleviate core deficits and have significant side effects. While many behavioral therapies are inadequate, a very intensive form called applied behavioral analysis (ABA) is demonstrably effective. ABA is based on graded progression and immediate feedback. ABA has raised concerns over its intensive nature and has triggered unease about being too harsh. One solution may derive from a widespread hypothesis of ASD pathogenesis, which posits that the brain in ASD is overexcited, i.e., excitation dominates over inhibition, and electroencephalographic (EEG) alpha band oscillatory activity is altered, which degrades sensory input and task management. This may also disrupt the brain mesolimbic dopaminergic reward cascade causing social interactions to be unrewarding, leading to deleterious social behavior and poor communication. We hypothesize that a comprehensive, personalized form of spectral EEG guided repetitive transcranial magnetic stimulation that we term PrTMS, can normalize alpha EEG oscillations, E/I balance, and dopaminergic reward signaling, to facilitate improved psychosocial behavior. The goal is for PrTMS to synergize with behavioral interventions, so that ABA for example, could be less intensive. This may hold the promise of making self-determination more readily attainable for ASD persons, and could also democratize ASD therapy by rendering it more affordable.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD). A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group. Aphthalate metabolite mixturewas associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium. Early childhood exposure to aphthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

Adult Symptoms of ASD and ADHD in Relation to Alcohol Use: Potential Roles of Transdiagnostic Features

Attention Deficit Hyperactivity Disorder (ADHD) is the most common comorbidity in Autism Spectrum Disorder (ASD). ADHD is a risk factor for alcohol misuse whereas ASD is often regarded as protective; however, research on ASD and alcohol use has yielded conflicting findings, sometimes implicating the role of comorbid ADHD. The possibility that certain transdiagnostic features (i.e., characteristics associated with multiple disorders) may underlie relationships of both disorders to alcohol use in adults was examined in the present study. A nonclinical young adult sample of 248 alcohol users (117 men, 131 women) completed validated self-report measures of ASD and ADHD symptoms as well as the transdiagnostic features alexithymia, impulsivity, and negative moods. ASD and ADHD symptoms were normally distributed, suggesting that the respective disorders represent extreme, dysfunctional ends of population distributions of symptoms. Path analysis indicated that the significant positive association between ASD and ADHD symptom measures was fully mediated by alexithymia, impulsivity, and negative moods. Hierarchical regression and path analysis indicated that the positive relationship between ADHD symptoms and alcohol use severity was fully mediated by transdiagnostic features, particularly alexithymia and impulsivity, whereas the relationship between ASD and alcohol use severity was positively mediated by these features (especially alexithymia), with a highly significant and negative direct effect. Present findings may help reconcile previous conflicting evidence on the relationship of ASD to alcohol use, and the role of comorbid ADHD, by emphasizing the roles of alexithymia and impulsivity in both ASD and ADHD as transdiagnostic traits promoting excessive drinking.

Altered Intrinsic Brain Spontaneous Activities in Children With Autism Spectrum Disorder Comorbid ADHD

Objective: The study involved 17 children with Autism Spectrum Disorder (ASD), 21 with ADHD, 30 with both (ASD + ADHD), and 28 typically developing children (TD). Methods: The amplitude of low-frequency fluctuations (ALFF) was measured as a regional brain function index. Intrinsic functional connectivity (iFC) was also analyzed using the region of interest (ROI) identified in ALFF analysis. Statistical analysis was done via one-way ANCOVA, Gaussian random field (GRF) theory, and post-hoc pair-wise comparisons. Results: The ASD + ADHD group showed increased ALFF in the left middle frontal gyrus (MFG.L) compared to the TD group. In terms of global brain function, the ASD group displayed underconnectivity in specific regions compared to the ASD + ADHD and TD groups. Conclusion: The findings contribute to understanding the neural mechanisms underlying ASD + ADHD.

Autism Spectrum Disorder: Brain Areas Involved, Neurobiological Mechanisms, Diagnoses and Therapies.

Autism spectrum disorder (ASD), affecting over 2% of the pre-school children population, includes an important fraction of the conditions accounting for the heterogeneity of autism. The disease was discovered 75 years ago, and the present review, based on critical evaluations of the recognized ASD studies from the beginning of 1990, has been further developed by the comparative analyses of the research and clinical reports, which have grown progressively in recent years up to late 2023. The tools necessary for the identification of the ASD disease and its related clinical pathologies are genetic and epigenetic mutations affected by the specific interaction with transcription factors and chromatin remodeling processes occurring within specific complexes of brain neurons. Most often, the ensuing effects induce the inhibition/excitation of synaptic structures sustained primarily, at dendritic fibers, by alterations of flat and spine response sites. These effects are relevant because synapses, established by specific interactions of neurons with glial cells, operate as early and key targets of ASD. The pathology of children is often suspected by parents and communities and then confirmed by ensuing experiences. The final diagnoses of children and mature patients are then completed by the combination of neuropsychological (cognitive) tests and electro-/magneto-encephalography studies developed in specialized centers. ASD comorbidities, induced by processes such as anxieties, depressions, hyperactivities, and sleep defects, interact with and reinforce other brain diseases, especially schizophrenia. Advanced therapies, prescribed to children and adult patients for the control of ASD symptoms and disease, are based on the combination of well-known brain drugs with classical tools of neurologic and psychiatric practice. Overall, this review reports and discusses the advanced knowledge about the biological and medical properties of ASD.

Atomoxetine Treatment of Attention Deficit/Hyperactivity Disorder Symptoms in 3-6-Year-Old Children with Autism Spectrum Disorder: A Retrospective Cohort Study.

Atomoxetine is indicated for the management of attention deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 18 years. Few studies have assessed the safety and tolerability of atomoxetine in younger patients. This retrospective cohort study included 133 children aged 3-6 years who were diagnosed with ADHD comorbid with autism spectrum disorder (ASD). The primary endpoint was the evaluation of the safety profile of atomoxetine. In total, 50 patients (37.6%) experienced adverse events (AEs), which led to treatment discontinuation in 23 patients (17.3%). The most common AEs were gastrointestinal (24.1%), aggression or hostility (12.8%), and increased hyperactivity (9.0%). In the 23 patients who discontinued treatment, all the AEs resolved after treatment ceased. Among the 110 patients who completed at least 6 months' treatment, atomoxetine titrated to a dose of 1.2-1.8 mg/kg/day appeared to be well tolerated and effective. The Clinical Global Impression-Improvement score improved to 1 ("very much improved") and 2 ("much improved") in 62.4% and 20.3% of children, respectively, at their last visit. Overall, atomoxetine appeared to be well tolerated in younger children with comorbid ADHD and ASD. Nevertheless, close patient monitoring remains essential, and the study limitations necessitate caution in generalizing these findings to broader populations. Long-term prospective studies are required.

Cannabidiol (Epidyolex®) for severe behavioral manifestations in patients with tuberous sclerosis complex, mucopolysaccharidosis type III and fragile X syndrome: protocol for a series of randomized, placebo-controlled N-of-1 trials

BackgroundMany rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design.MethodsWe aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants’ natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials.DiscussionThese N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level.Trial registrationEudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL.

Gray matter asymmetry alterations in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder.

Despite the high coexistence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) (ASD + ADHD), the underlying neurobiologicalbasis of this disorder remains unclear. Altered brain structural asymmetries have been verified in ASD and ADHD, respectively, making brain asymmetry a candidate for characterizing this coexisting disorder. Here, we measured the gray matter (GM) volume asymmetry in ASD + ADHD versus ASD without ADHD (ASD-only), ADHD without ASD (ADHD-only), and typically developing controls (TDc). High-resolutionT1-weighted data from 48 ASD + ADHD, 63 ASD-only, 32 ADHD-only, and 211 matched TDc were included in our study. We also assessed brain-behavior relationships and the effects of age on GM asymmetry. We found that there were both shared and disorder-specific GM volume asymmetry alterations in ASD + ADHD, ASD-only, and ADHD-only compared with TDc. This finding demonstrates that ASD + ADHD is neither an endophenocopy nor an additive pathology of ASD and ADHD, but an entirely different neuroanatomical pathology. In addition, ASD + ADHD displayed altered GM volume asymmetries in the prefrontal regions responsible for executive function and theory of mind compared with ASD-only. We also found significant effects of age on GM asymmetry. The present study may provide structural insights into the neural basis of ASD + ADHD.

SNAP-25 Polymorphisms in Autism Spectrum Disorder: A Pilot Study towards a Possible Endophenotype.

While there is substantial agreement on the diagnostic criteria for autism spectrum disorder, it is also acknowledged that it has a broad range of clinical presentations. This can complicate the diagnostic process and aggravate the choice of the most suitable rehabilitative strategy for each child. Attentional difficulties are among the most frequently reported comorbidities in autism spectrum disorder. We investigated the role of SNAP-25 polymorphisms. Synaptosome-associated protein 25 (SNAP25) is a presynaptic membrane-binding protein; it plays a crucial role in neurotransmission and has already been studied in numerous psychiatric disorders. It was also seen to be associated with hyperactivity in children with autism spectrum disorder. We collected clinical, behavioral and neuropsychological data on 41 children with a diagnosis of autism spectrum disorder, and then genotyped them for five single-nucleotide polymorphisms of SNAP-25. Participants were divided into two groups according to the Autism Diagnostic Observation Schedule (ADOS-2) Severity Score. In the group with the highest severity score, we found significant associations of clinical data with polymorphism rs363050 (A/G): children with the GG genotype had lower total IQ, more severe autistic functioning and more attentional difficulties. Our research could be the starting point for outlining a possible endophenotype among patients with autism spectrum disorder who are clinically characterized by severe autistic functioning and significant attentional difficulties.

Management of sleep disorders in autism spectrum disorder with co-occurring attention-deficit hyperactivity disorder: update for clinicians.

To update and examine available literature germane to the recognition, assessment and treatment of comorbid autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and sleep disruption, with a predominant focus on children, adolescents and emerging adults. Considerable overlaps exist among ASD, ADHD and sleep disruption. Literature and guidance for clinicians, administrators, policy makers and families have been limited, as such deliberations were rarely considered until 2013. This narrative review of the literature addressing sleep disruption issues among those with ASD, ADHD and comorbid ASD and ADHD involved searching multiple databases and use of reverse citations up to the end of September 2022. Emphasis is placed on secondary sources and relevant data for clinical practice. Complex clinical presentations of ASD/ADHD/sleep disruption are frequently encountered in clinical practice. Prior to 2013, prevalence, clinical presentation, pathophysiology, prognosis, other sleep-related factors and interventions were determined separately for each disorder, often with overlapping objective and subjective methods employed in the process. High percentages of ADHD and ASD patients have both disorders and sleep disruption. Here, the extant literature is integrated to provide a multidimensional understanding of the relevant issues and insights, allowing enhanced awareness and better care of this complex clinical population. Database limitations are considered. Assessment of ASD symptomatology in youth with ADHD, and the reverse, in cases with disrupted sleep is critical to address the special challenges for case formulation and treatment. Evidence-based approaches to treatment planning and multi-treatment modalities should consider combining psychosocial and biological interventions to address the complexities of each case.

Cause-specific mortality and comorbid neurodevelopmental disorder in 167,515 patients with bipolar disorder: An entire population longitudinal study

ObjectiveStudies addressing premature mortality in bipolar disorder (BD) patients are limited by small sample sizes. Herein, we used almost 99 % of the population of Taiwan to address this issue, and its association with comorbid neurodevelopmental disorders and severe BD. MethodsBetween 2003 and 2017, we enrolled 167,515 individuals with BD and controls matched 1:4 for sex and birth year from the National Health Insurance Database linked to the Database of National Death Registry in Taiwan. Time-dependent Cox regression models were used to examine cause-specific mortality (all-cause, natural, and unnatural causes [accidents or suicide]). ResultsWith adjustments of sex, age, income, urbanization, and physical conditions, suicide was associated with the highest risk of mortality (reported as hazard ratio with 95 % confidence interval: 9.15; 8.53–9.81) among BD patients, followed by unnatural (4.94; 4.72–5.17), accidental (2.15; 1.99–2.32), and natural causes (1.02; 1.00–1.05). Comorbid attention-deficiency hyperactivity disorder did not contribute to the increased risk of cause-specific mortality; however, comorbid autism spectrum disorder (ASD) increased such risks, particularly for natural (3.00; 1.85–4.88) and accidental causes (7.47; 1.80–31.1). Cause-specific mortality revealed a linear trend with the frequency of psychiatric hospitalization (all, p for trend <0.001), and BD patients hospitalized twice or more each year had 34.63-fold increased risk of suicide mortality (26.03–46.07). ConclusionsBD patients with a higher frequency of psychiatric hospitalization have the highest risk of suicide mortality, and comorbid ASD was associated with an increased risk of natural and accidental causes of mortality.

Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder

Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography–mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

80 Implications of Body Mass Index on Executive Functioning in Clinically Diagnosed Neurodiverse Children

Objective:Childhood obesity is a serious health epidemic affecting the world today. Children who are obese earlier in life are more likely to stay obese and have an increased risk of poorer health outcomes later in life, such as diabetes and cardiovascular diseases. Obesity is also associated with deficits in executive function. Executive function (EF) is comprised of several distinct but interrelated abilities including working memory, planning, inhibition, and flexibility. Prior research suggests that obesity drives brain changes which implicate executive function structures. Our aim is to examine the relationship between childhood obesity and executive function in children with neurodevelopmental disorders.Participants and Methods:These data are from an ongoing study on neural and behavioral phenotypes of executive functioning in children with developmental disabilities, primarily Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Only study participants with complete BMI and BRIEF data were included in these analyses (n = 184). 134 representing (72.8%) of the participants were Male, 49 representing (26.6%) were Female, and 1 representing (.5%) were Gender nonconforming. 50 representing (27.2%) of the participants were between 8-9 years, 55 representing (29.9%) were between 10-11 years, and 80 representing (43.0%) were between 12-13 years. Average age was 11 years. 11 representing (6.0%) of the participants were underweight, 115 representing (62.5%) were healthy, 29 representing (15.8%) were overweight, and 29 representing (15.8%) were obese. Average BMI was 19.0, ranging from 13.2 to 36.3. 106 representing (57.6%) of the participants identified as White, 65 representing (35.3%) identified as BIPOC (2 Asian, 31 Hispanic/Latinx, 32 Black) and 13 representing (4.4%) identified as other/unspecified. 114 representing (61.9%) of the participants had a diagnosis of ADHD, ASD, or comorbid ASD and ADHD, 70 representing (38.1%) had a diagnosis of other. Average FSIQ-2 score was 106.98. Parents were asked to complete the Behavior Rating Inventory of Executive Function (BRIEF-2) and the Inhibit, Shift, Working Memory (WM), Planning, and Global Executive Composite (GEC) scales were used as the dependent measure in analyses. BMI (kg/mA2) was calculated based on CDC 2000 growth charts and classified into 4 mutually exclusive categories—underweight, healthy, overweight, and obese. There was a prediction that higher BMI would be associated with lower executive function.Results:A one-way ANOVA revealed a statistically significant difference between groups (F(3,180) = 3.649, p = .014). A Tukey post hoc test revealed more Shift problems in the obese group (74.55 ± 11.7) compared to the overweight group (65.79 ± 11.6, p = .026). There was no statistically significant difference between the underweight/healthy and obese groups (p = .999/p = .054). There was no statistically significant difference in mean T-scores for the Inhibit, WM, Planning, or GEC scales.Conclusions:Childhood obesity and executive function deficits are significant risk factors for adult health outcomes. Obesity and elevated executive function T-scores for flexibility are related in a group of children with neurodevelopmental disorders. Future investigation will explore the role of cortical thickness and medication in these data.

Peripheral markers of nitrosative stress in children with autism spectrum disorder and bipolar disorder comorbidity during euthymic phase

BackgroundBipolar Disorder (BD) is often comorbid with Autism Spectrum Disorder (ASD) (Skokauskas & Frodl, 2015). However, to our knowledge, the etiological pathways of BD comorbidity in individuals with ASD was not given a particular focus in the literature. The present study aims to investigate the link between BD comorbidity and nitrosative stress in children and adolescents with ASD. MethodThe case group consisted of 41 participants with comorbid ASD and BD, while the control group consisted of 39 participants with ASD who did not have any past or present mood disorders. As indicators of nitrosative stress, serum levels of NO (Nitric Oxide), NO2/NO3 (Nitrite/Nitrate), 3-NT (3-Nitrotyrosine) and NOS-I (Nitric Oxide Synthetase-I) were compared between groups. ResultsSerum levels of NO and 3-NT were significantly higher in the case group. As the phenomenological findings of BD, the age of onset was 10.5, mixed attack rate was 70%, seasonality rate was 63.8%, and sub-threshold symptoms were seen in 36.6% of the cases. ConclusionThe present study indicated a relationship between BD comorbidity and nitrosative stress cascade among children and adolescents with ASD. Further studies with larger samples are needed to better understand the etiology of BD comorbidity in patients with ASD.

A multi-task learning model with reinforcement optimization for ASD comorbidity discrimination

How to discriminate the comorbidities in autism spectrum disorder (ASD) population has long been an intriguing and challenging issue in neuroscience and neurology practices. Taking attention deficit hyperactivity disorder (ADHD) for example, electroencephalogram (EEG) analysis has alleviated the problem caused by the task of evaluation of similar behaviors of subjects with ASD, ADHD and ASD+ADHD, which requires a very high expertise to reach any concrete conclusions. However, the performance of ASD comorbidity discrimination is still limited by two major difficulties 1) crucial EEG features regarding ASD and ASD+ADHD largely overlap, and 2) reliable data for model training are routinely insufficient.This study proposes a multi-task learning method with “reinforcement optimization” (namely RO-MLT) working in a two-fold manner: 1)Modeling for Discrimination: a multi-task CNN model maintains the target discrimination task (ASD vs. ASD+ADHD) with the aid of the auxiliary task (ASD vs. Typically Developed (TD)), which is designed to mitigate the aforementioned difficulties on model training; and 2) Reinforcement Optimization: a reinforcement learning algorithm enhances the model's feature extraction and fusion capabilities by optimizing its shared structure.Experimental results based on resting-state EEG that collected from 150 ASD, ASD+ADHD or TD children with the RO-MLT method against the state-of-the-art counterparts indicate that RO-MLT is far superior in terms of all performance indicators (e.g., accuracy). Ablation experiments also show that introduction of multi-task learning and reinforcement optimization can achieve a performance boost-up by 11.07%, a gain even higher than the sums of introduction of two individual techniques to the model design.