Comparative review of Gilbert’s Syndrome, Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: Etiology, presentation, and clinical implications

Autism symptoms in children with attention-deficit/hyperactivity disorder: a community-based study

The impairment of inhibitory control is often assumed to be the core deficit of several neurodevelopmental disorders characterized by poor impulse control. However, could the same deficit explain different clinical phenotypes? Evidence from behavioural studies is very mixed. This is partly because inhibition is a highly complex executive function. Thus, the different types of tasks that generically tap into inhibitory control are likely to provide different outcomes. Additionally, sample inhomogeneity in terms of age, comorbidity, and medical treatment are confounding factors. Therefore, to make a reliable assessment of the deficit of inhibitory control in a given disorder, the same task and samples with similar characteristics must be employed. This article reviews and discusses studies on five neurodevelopmental disorders with impaired impulse control where these criteria have been used: Tourette syndrome; obsessive-compulsive disorder; attention-deficit/hyperactivity disorder; primary motor stereotypies; and autism spectrum disorder. Overall, they suggest that the mechanisms underlying the inability to control urges are extremely heterogeneous and cannot be ascribed to a general impairment of inhibition. These findings do not support the hypothesis that inhibitory deficits represent a transdiagnostic feature of neurodevelopmental disorders with poor impulse control. WHAT THIS PAPER ADDS: The mechanisms underlying the inability to control urges in neurodevelopmental disorders are heterogeneous. Inhibition impairments cannot generally explain all neurodevelopmental disorders characterized by poor urge control.

Objective:Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are neurodevelopmental disorders with overlapping symptomatology and shared genetic makeup. Numerous previous studies have investigated ASD and ADHD using resting state functional networks. One functional network of particular interest is the Default Mode Network (DMN), as it has been shown to be abnormal in several mental disorders. Previous studies have investigated the DMN in ASD and ADHD separately but reported mixed trends of increased and decreased functional connectivity (FC) in the DMN in ASD and increased FC in ADHD. Additionally, little studies have investigated executive and attentional network dysfunction in the DMN for ASD and ADHD populations. To better understand the shared characteristics between ASD and ADHD, this study analyzed the DMN FC in children with ASD and ADHD.Participants and Methods:Archival datasets from Autism Brain Imaging Data Exchange (ABIDE)-I and ADHD-200 datasets were used, with 33 ADHD, 35 ASD, and 32 typically developing (TD) males (ages = 7-17 years). After applying a standard pre-processing pipeline, 11 regions of interest (ROIs) from the Dosenbach-160 atlas were examined with 55 ROI pairs generated for the 100 subjects.Results:Significant differences were noted between ASD-ADHD groups in attentional networks and executive functioning networks. Specifically, significant Group x VIQ interactions were noted for FC between the following pairs of regions: medial prefrontal cortex - ventromedial prefrontal cortex, anterior cingulate cortex -ventromedial prefrontal cortex, inferior temporal lobe - ventromedial prefrontal cortex, angular -ventromedial prefrontal cortex, angular -anterior cingulate cortex, inferior temporal lobe -ventrolateral prefrontal cortex, angular -superior frontal lobe, and intraparietal sulcus -superior frontal lobe. In the above FC pairs, FC in ADHD was negatively correlated with VIQ, with no correlation for ASD and positive correlation for TD. Previous literature has indicated that ADHD individuals demonstrate increased executive functioning deficits compared to ASD individuals. This study provides evidence at a neural level for these findings by demonstrating decreased FC trends in ADHD in attentional and executive functioning networks compared to ASD individuals. Group and VIQ main effects demonstrated mixed patterns across the three groups, as well as shared decreased FC in attention/executive networks for both ASD and ADHD groups.Conclusions:In summary, this study found similar findings from previous studies regarding mixed connectivity patterns, as well as shared dysfunction between ASD and ADHD groups. These results help in solidifying the theory that ASD and ADHD share clinical and neural patterns which need to be examined further. Future directions include utilizing more ASD+ADHD comorbid individuals in studies comparing ASD and ADHD FC trends as well as seeking to further understand the neuropsychological and neuroimaging profiles in ASD and ADHD.

Background: Social-communication difficulties, a hallmark of ASD, autism spectrum disorder (ASD) are often observed in attention – deficit/ hyperactivity disorder (ADHD), although are not part of its diagnostic criteria. Despite sex differences in the prevalence of ASD and ADHD, research examining how sex differences manifest in social and communication functions in these disorders remains limited, and findings are mixed. This study investigated potential sex differences with age in social adaptive function across these disorders, relative to controls. Method: One hundred fifteen youth with ASD, 172 youth with ADHD, and 63 typically developing controls (age range 7–13 years, 75% males) were recruited from the Province of Ontario Neurodevelopmental Disorder (POND) Network. Social adaptive function was assessed using the Adaptive Behavior Assessment System-Second Edition (ABAS-II). The proportions of adaptive behaviors present in each skill area were analyzed as a binomial outcome using logistic regression, controlling for age, and testing for an age-by-sex interaction. In an exploratory analysis, we examined the impact of controlling for core symptom severity on the sex effect. Results: Significant sex-by-age interactions were seen within ASD in the communication (p = 0.005), leisure (p = 0.003), and social skill areas (p < 0.0001). In all three areas, lower scores (indicating poorer function) were found in females compared to males at older ages despite females performing better at younger ages. There were significant differences in the sex-by-age interactions in the social and leisure domains between those with ASD and typically developing controls, with typically developing females showing better scores at older, compared to younger, ages. There were also significant differences in the sex-by-age interactions between ASD and ADHD on the social and leisure domains, as females with ADHD consistently scored higher on social skills than males across all ages, unlike those with ASD. Sex differences across age in the social domains for ADHD were similar to those in the typically developing group. Conclusion: Sex differences in social and communication skill areas were observed between ASD and ADHD, and typically developing controls, with females with ASD performing worse than males at older ages, despite an earlier advantage. These findings reinforce the need to take a developmental approach to understanding sex differences which may have diagnostic, prognostic, and treatment implications.

ABSTRACTBackgroundEarly‐onset neonatal infections are among the most common neonatal diseases. However, the long‐term outcomes of the infections are not well understood.ObjectiveTo study the association between early‐onset neonatal infection and attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).MethodsA nationwide register‐based cohort study was conducted, including near‐term and term children born between 1997 and 2013 with follow‐up until 2021. An early‐onset infection was defined as an invasive bacterial infection occurring within the first week of life, including both physician‐assigned diagnoses and positive bacterial cultures. ADHD and ASD were defined by diagnoses or prescriptions of relevant medication. Associations between sepsis and the neurodevelopmental disorders were investigated using multivariable Cox regression to estimate adjusted hazard ratios (HR), whereas associations with meningitis were examined using person‐time incidence rate ratios (IRR). Sibling‐matched analyses were also conducted for associations with sepsis.ResultsA total of 981,869 children were included, with 8154 defined as having sepsis and 152 defined as having meningitis. Among these, only 257 children had culture‐positive sepsis, whereas 32 had culture‐positive meningitis. The incidence rate of ADHD and ASD for children with sepsis was 4.5 per 1000 and 3.3 per 1000 person‐years, respectively. Sepsis was associated with an increased adjusted likelihood of both ADHD (HR 1.28, 95% CI 1.17, 1.39) and ASD (HR 1.43, 95% CI 1.30, 1.58). However, sibling‐matched analyses especially attenuated the association with ADHD (HR 1.12, 95% CI 0.93, 1.34). Point estimates suggested that children with meningitis also had an increased likelihood of both ADHD (IRR 1.77, 95% CI 0.88, 3.17) and ASD (IRR 2.05, 95% CI 0.89, 4.04).ConclusionsEarly‐onset sepsis was associated with an increased likelihood of ASD, whereas the majority of the association with ADHD could be explained by unmeasured shared familial confounding.

Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction.

Background/Objectives: Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are neurodevelopmental disorders (NDDs) with overlapping symptoms, suggesting a partially shared genetic origin. This study investigates the prevalence of connective tissue-related conditions in individuals with ASD, ADHD, or TS. Methods: A questionnaire was administered to families of 120 individuals with ASD, ADHD, or TS, collecting sociodemographic data and examining 10 types of disorders affecting various organs and systems. Statistical analyses were performed using STATA 16.0, with the significance level set at 5%. Results: Among the 120 patients, 48 had ASD, 36 had ADHD, and 36 had TS. Flat feet were significantly more common in individuals with ASD (52.1%; OR 7.20; p < 0.001), ADHD (52.8%; OR 6.73; p = 0.001), and TS (38.9%; OR 3.70; p = 0.034) compared to controls (13.6%). Hypersensitivity was more frequent in individuals with ASD (56.3%; OR 5.90; p = 0.001), ADHD (50.0%; OR 4.11; p = 0.011), and TS (58.3%; OR 5.35; p = 0.003) compared to controls (18.2%). Myopia and ptosis were more common in ADHD (30.6%). There was a possible trend towards orthodontic device use in TS (OR 3.20; p = 0.076). Flat feet and hypersensitivity were also common in fathers (31.0% and 36.4%, respectively), mothers (31.0% and 15.2%), and patients (43.8% and 55%). Conclusions: The findings of this study highlight the significant associations between ASD, ADHD, and TS and specific physical symptoms, such as flat feet, sensory hypersensitivity, and other connective tissue-related manifestations. The familial prevalence of these symptoms suggests a potential genetic underpinning, further supporting the hypothesis of shared aetiological pathways. These insights underscore the need for interdisciplinary research to explore the mechanisms linking neurodevelopmental and connective tissue disorders, aiming to improve diagnosis and management strategies.

Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome

BackgroundThe continuous performance task (CPT) may help identify coexistent attention deficit hyperactivity disorder (ADHD) in autism spectrum disorder (ASD). The Quantified behavior Test (QbTest) combines a CPT and motion-tracking data to assess ADHD symptoms. This study aimed to evaluate the QbTest performance of children and adolescents with ASD plus ADHD, including estimating the effects of single-dose methylphenidate (MPH). To achieve these aims, (1) the QbTest performances were evaluated in ASD alone, ASD plus ADHD, and ADHD alone, and (2) the effects on the QbTest performance of single-dose MPH before and after intake were estimated across the groups. It was assumed that the ASD plus ADHD performance, including the MPH response, would preferably resemble the performance in ADHD alone, rather than ASD alone.MethodsRetrospective data were analyzed for 482 children and adolescents: 69 with ASD alone, 142 with ASD plus ADHD (ASD/ADHD), and 271 with ADHD alone. For 343 subjects, the QbTest was performed before and up to four hours after a single-dose MPH intake. A summary index of the CPT and motion-capture data was provided for QbTest cardinal parameters.ResultsOf 12 QbTest parameters assessed before given MPH, the ASD/ADHD group had scores in line with the ASD group regarding four parameters and the ADHD group regarding nine parameters. Significant differences between groups were seen with respect to QbInattention (p > 0.05); the lowest scores in ASD and the highest in ADHD. Those with ASD/ADHD and ADHD had similar QbActivity and QbImpulsivity scores, but significantly higher than those with ASD. After MPH intake, scores for QbActivity decreased similarly in ASD/ADHD and ADHD, as well as scores for QbImpulsivity. QbImpulsivity increased in ASD. QbInattention scores decreased similarly in all groups after MPH intake.ConclusionsChildren and adolescents with ASD plus ADHD exhibited more atypical QbTest performances than those with ASD alone, while most of their performances were similar to those observed in ADHD alone. In addition, a single dose of MPH mitigated attention deficits and decreased hyperactivity while improved impulsivity in these children. Prospective studies should further clarify the role of the QbTest in the diagnostic and therapeutic interventions in ASD with ADHD.

Hair trace element concentrations in autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD)

Gut microbiome differences in children with Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder and effects of probiotic supplementation: A randomized controlled trial.

BackgroundTo diagnose and manage adults with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), or their co-occurrence (ADHD + ASD), clinicians must identify specific features that differentiate these diagnostic categories. Self-report questionnaires targeting specific features are widely used and, together with clinical assessments, provide reliable diagnoses. Although affective lability is present in various psychiatric disorders, it lacks specificity when screening for ADHD in the general population, and its discriminant value for ADHD, ASD, and ADHD + ASD has not been studied.MethodsThis study involved 300 adults without intellectual developmental disorder (188 male) who received an ADHD (n = 174), ASD (n = 68), or ADHD + ASD (n = 58) diagnosis after a multidisciplinary consensus decision according to DSM-5 criteria. Before clinical assessment, all patients requesting evaluation for one of these diagnoses completed questionnaires on an online platform. The assessment instruments included a modified version of the Barkley Adult ADHD Rating Scale (BAARS IV) for ADHD, the Autism Spectrum Quotient (AQ) and the Empathy Quotient (EQ) for ASD features, and the Affective Lability Scale (ALS) for affective lability. Total scores and sub-scores of the instruments were compared among the three groups. Additionally, stepwise logistic regression analyses were conducted to identify specific measures that contribute to group discrimination.ResultsResults revealed distinct patterns in symptomatology as expected. The ADHD and the ADHD + ASD groups presented significantly higher ALS total score compared to ASD. Stepwise logistic regression analyses identified specific measures contributing to group differentiation. ASD vs. ADHD + ASD discrimination included BAARS IV current total score and EQ total score. The subscale anger from ALS in addition with BAARS IV past total score and AQ total score were the factors that discriminated ADHD diagnosis from the co-occurrence of ADHD and ASD. Finally, BAARS IV past total score, BAARS IV current inattention, AQ total score, and EQ total score were found to differentiate ADHD from ASD.ConclusionsThe study highlights the significance of incorporating emotional dimensions in diagnostic frameworks and may contribute valuable insights for clinicians differentiating neurodevelopmental conditions.

Association of Anemia with Neurodevelopmental Disorders in a Nationally Representative Sample of US Children

This study examined the neuropsychological functioning in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and comorbid ASD and ADHD (ASD + ADHD), using five domains of the Developmental Neuropsychological Assessment (NEPSY): Attention and Executive Functions, Language, Visuospatial Processing, Sensorimotor Functions, and Memory and Learning. The participants were 6- to 12-year-old Egyptian children with ASD (n = 17), ASD + ADHD (n = 15), ADHD (n = 37), and typical development (TD; n = 29). TD children scored highest on the NEPSY domains, then children with ADHD, followed by children with ASD and ASD + ADHD. Children with ASD or ASD + ADHD performed significantly poorer than TD children on all NEPSY domains. Children with ADHD exhibited significantly poorer performance than TD children on NEPSY domains of Attention and Executive Function, Language, and Memory and Learning. Also, both ASD and ASD + ADHD groups scored significantly lower than ADHD group on all other NEPSY domains except Visuospatial Processing. There were no significant differences between ASD and ASD + ADHD groups on NEPSY. Compared to TD children, our results suggest that ADHD symptoms in children with ASD may worsen the ability to plan, hand motor coordination, and memorizing names. Nevertheless, the presence of ADHD symptoms may mitigate the difficulties that children with ASD exhibit in other neuropsychological areas, such as verbal fluency, hand praxis, finger gnosis, and face memory.

BackgroundUnderstanding how individuals think about a topic, known as the mental model, can significantly improve communication, especially in the medical domain where emotions and implications are high. Neurodevelopmental disorders (NDDs) represent a group of diagnoses, affecting up to 18% of the global population, involving differences in the development of cognitive or social functions. In this study, we focus on 2 NDDs, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which involve multiple symptoms and interventions requiring interactions between 2 important stakeholders: parents and health professionals. There is a gap in our understanding of differences between mental models for each stakeholder, making communication between stakeholders more difficult than it could be.ObjectiveWe aim to build knowledge graphs (KGs) from web-based information relevant to each stakeholder as proxies of mental models. These KGs will accelerate the identification of shared and divergent concerns between stakeholders. The developed KGs can help improve knowledge mobilization, communication, and care for individuals with ADHD and ASD.MethodsWe created 2 data sets by collecting the posts from web-based forums and PubMed abstracts related to ADHD and ASD. We utilized the Unified Medical Language System (UMLS) to detect biomedical concepts and applied Positive Pointwise Mutual Information followed by truncated Singular Value Decomposition to obtain corpus-based concept embeddings for each data set. Each data set is represented as a KG using a property graph model. Semantic relatedness between concepts is calculated to rank the relation strength of concepts and stored in the KG as relation weights. UMLS disorder-relevant semantic types are used to provide additional categorical information about each concept’s domain.ResultsThe developed KGs contain concepts from both data sets, with node sizes representing the co-occurrence frequency of concepts and edge sizes representing relevance between concepts. ADHD- and ASD-related concepts from different semantic types shows diverse areas of concerns and complex needs of the conditions. KG identifies converging and diverging concepts between health professionals literature (PubMed) and parental concerns (web-based forums), which may correspond to the differences between mental models for each stakeholder.ConclusionsWe show for the first time that generating KGs from web-based data can capture the complex needs of families dealing with ADHD or ASD. Moreover, we showed points of convergence between families and health professionals’ KGs. Natural language processing–based KG provides access to a large sample size, which is often a limiting factor for traditional in-person mental model mapping. Our work offers a high throughput access to mental model maps, which could be used for further in-person validation, knowledge mobilization projects, and basis for communication about potential blind spots from stakeholders in interactions about NDDs. Future research will be needed to identify how concepts could interact together differently for each stakeholder.