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Parents of children with ASD who had attended an Australian emergency department (ED; n = 421) completed a questionnaire relating to their experiences in the ED, including (1) child's reason for presentation and existing comorbidities, (2) quality of care during the visit (3) child's behaviour during visit, e.g. sensory responses to the ED environment, and disruptive behaviours. Children with comorbid ASD and intellectual disability were more likely to present with gastrointestinal issues and seizures, while those with comorbid ASD and oppositional defiant disorder were more likely to present with self-injury. ED staff awareness of ASD-related issues, including communication and expression of pain, were common difficulties for parents. The ED environment (e.g. lights, sounds, waiting areas), exacerbated child anxiety and led to disruptive behaviour.

The clinical heterogeneity of autism spectrum disorders majorly challenges their genetic study. Autism spectrum disorders symptoms occur in milder forms in the general population, as autistic-like traits, and share genetic factors with autism spectrum disorders. Here, we investigate the genetics of individual autistic-like traits to improve our understanding of autism spectrum disorders. We meta-analysed four population-based genome-wide association studies investigating four autistic-like traits -- 'attention-to-detail', 'imagination', 'rigidity' and 'social-skills' (n = 4600). Using autism spectrum disorder summary statistics from the Psychiatric Genomic Consortium (N = 46,350), we applied polygenic risk score analyses to understand the genetic relationship between autism spectrum disorders and autistic-like traits. Using MAGMA, we performed gene-based and gene co-expression network analyses to delineate involved genes and pathways. We identified two novel genome-wide significant loci -- rs6125844 and rs3731197 -- associated with 'attention-to-detail'. We demonstrated shared genetic aetiology between autism spectrum disorders and 'rigidity'. Analysing top variants and genes, we demonstrated a role of the immune-related genes "RNF114," "CDKN2A," "KAZN," "SPATA2" and "ZNF816A" in autistic-like traits. Brain-based genetic expression analyses further linked autistic-like traits to genes involved in immune functioning, and neuronal and synaptic signalling. Overall, our findings highlight the potential of the autistic-like trait-based approach to address the challenges of genetic research in autism spectrum disorders. We provide novel insights showing a potential role of the immune system in specific autism spectrum disorder dimensions.

Objective: Growing evidence suggests digital interventions may provide neurocognitive benefits for children with ADHD. This study aimed to investigate the efficacy of a digital attention intervention in children with ADHD. Method: In this double-blind randomized controlled trial 55 children with ADHD (5–9 years) were allocated to the intervention (N = 28) or control program (N = 27). Both programs were delivered via touchscreen tablets at home 5 days a week for 5 weeks. The primary outcome was change in the Test of Variables of Attention (TOVA) Attention Comparison Score (ACS) from pre- to post-intervention. Results: Participants who received the intervention had significantly greater improvements in the TOVA ACS from pre- to post-intervention than those in the control (p <.044). No intervention effects were observed on secondary outcomes assessing executive functioning, ADHD symptoms, or functional impairment. Conclusion: Collectively these findings provide insufficient evidence for the implementation of digital attention interventions for children with ADHD. [ABSTRACT FROM AUTHOR]

Executive Function (EF) and Effortful Control (EC) have traditionally been viewed as distinct constructs related to cognition and temperament during development. More recently, EF and EC have been implicated in top-down self-regulation - the goal-directed control of cognition, emotion, and behavior. We propose that executive attention, a limited-capacity attentional resource subserving goal-directed cognition and behavior, is the common cognitive mechanism underlying the self-regulatory capacities captured by EF and EC. We addressed three related questions: (a) Do behavioral ratings of EF and EC represent the same self-regulation construct? (b) Is this self-regulation construct explained by a common executive attention factor as measured by performance on cognitive tasks? and (c) Does the executive attention factor explain additional variance in attention deficit hyperactivity disorder (ADHD) problems to behavioral ratings of self-regulation? Measures of performance on complex span, general intelligence, and response inhibition tasks were obtained from 136 preadolescent children (M = 11 years, 10 months, SD = 8 months), along with self- and parent-reported EC, and parent-reported EF, and ADHD problems. Results from structural equation modeling demonstrated that behavioral ratings of EF and EC measured the same self-regulation construct. Cognitive tasks measured a common executive attention factor that significantly explained 30% of the variance in behavioral ratings of self-regulation. Executive attention failed to significantly explain additional variance in ADHD problems beyond that explained by behavioral ratings of self-regulation. These findings raise questions about the utility of task-based cognitive measures in research and clinical assessment of self-regulation and psychopathology in developmental samples.

Background: Autistic traits are often reported to be elevated in children diagnosed with attention‐deficit/hyperactivity disorder (ADHD). However, the distribution of subclinical autistic traits in children with ADHD has not yet been established; knowing this may have important implications for diagnostic and intervention processes. The present study proposes a preliminary model of the distribution of parent‐reported ADHD and subclinical autistic traits in two independent samples of Australian children with and without an ADHD diagnosis. Methods: Factor mixture modelling was applied to Autism Quotient and Conners' Parent Rating Scale – Revised responses from parents of Australian children aged 6–15 years who participated in one of two independent studies. Results: A 2‐factor, 2‐class factor mixture model with class varying factor variances and intercepts demonstrated the best fit to the data in both discovery and replication samples. The factors corresponded to the latent constructs of 'autism' and 'ADHD', respectively. Class 1 was characterised by low levels of both ADHD and autistic traits. Class 2 was characterised by high levels of ADHD traits and low‐to‐moderate levels of autistic traits. The classes were largely separated along diagnostic boundaries. The largest effect size for differences between classes on the Autism Quotient was on the Social Communication subscale. Conclusions: Our findings support the conceptualisation of ADHD as a continuum, whilst confirming the utility of current categorical diagnostic criteria. Results suggest that subclinical autistic traits, particularly in the social communication domain, are unevenly distributed across children with clinically significant levels of ADHD traits. These traits might be profitably screened for in assessments of children with high ADHD symptoms and may also represent useful targets for intervention. [ABSTRACT FROM AUTHOR]

Exercise is known to benefit motor skill learning in health and neurological disease. Evidence from brain stimulation, genotyping, and Parkinson’s disease studies converge to suggest that the dopamine D2 receptor, and shifts in the cortical excitation and inhibition (E:I) balance, are prime candidates for the drivers of exercise-enhanced motor learning. However, causal evidence using experimental pharmacological challenge is lacking. We hypothesized that the modulatory effect of the dopamine D2 receptor on exercise-induced changes in the E:I balance would determine the magnitude of motor skill acquisition. To test this, we measured exercise-induced changes in excitation and inhibition using paired-pulse transcranial magnetic stimulation (TMS) in 22 healthy female and male humans, and then had participants learn a novel motor skill-the sequential visual isometric pinch task (SVIPT). We examined the effect of D2 receptor blockade (800 mg sulpiride) on these measures within a randomized, double-blind, placebo-controlled design. Our key result was that motor skill acquisition was driven by an interaction between the D2 receptor and E:I balance. Specifically, poorer skill learning was related to an attenuated shift in the E:I balance in the sulpiride condition, whereas this interaction was not evident in placebo. Our results demonstrate that exercise-primed motor skill acquisition is causally influenced by D2 receptor activity on motor cortical circuits. [ABSTRACT FROM AUTHOR]

Objective: Reward‐based eating drives are putative mechanisms of uncontrolled eating implicated in obesity and disordered eating (e.g., binge eating). Uncovering the genetic and environmental contributions to reward‐related eating, and their genetic correlation with BMI, could shed light on key mechanisms underlying eating and weight‐related disorders. Method: We conducted a classical twin study to examine how much variance in uncontrolled eating phenotypes and body mass index (BMI) was explained by genetic factors, and the extent that these phenotypes shared common genetic factors. 353 monozygotic twins and 128 dizygotic twins completed the Reward‐based Eating Drive 13 scale, which measures three distinct uncontrolled eating phenotypes (loss of control over eating, preoccupation with thoughts about food, and lack of satiety), and a demographic questionnaire which included height and weight for BMI calculation. We estimated additive genetic (A), common environmental (C), and unique environmental (E) factors for each phenotype, as well as their genetic correlations, with a multivariate ACE model. A common pathway model also estimated whether genetic variance in the uncontrolled eating phenotypes was better explained by a common latent uncontrolled eating factor. Results: There were moderate genetic correlations between uncontrolled eating phenotypes and BMI (.26–.41). Variance from the uncontrolled eating phenotypes was also best explained by a common latent uncontrolled eating factor that was explained by additive genetic factors (52%). Discussion: These results suggest that uncontrolled eating phenotypes are heritable traits that also share genetic variance with BMI. This has implications for understanding the cognitive mechanisms that underpin obesity and disordered eating. Public Significance: Our study clarifies the degree to which uncontrolled eating phenotypes and BMI are influenced by shared genetics and shows that vulnerability to uncontrolled eating traits is impacted by common genetic factors. [ABSTRACT FROM AUTHOR]

Common variants account for most of the estimated heritability associated with autism spectrum disorder (autism). Although several replicable single nucleotide polymorphisms (SNPs) for the condition have been detected using genome‐wide association study (GWAS) methodologies, their pathophysiological relevance remains elusive. Examining this is complicated, however, as all detected loci are situated within non‐coding regions of the genome. It is therefore likely that they possess roles of regulatory function as opposed to directly affecting gene coding sequences. To bridge the gap between SNP discovery and mechanistic insight, we applied a comprehensive bioinformatic pipeline to functionally annotate autism‐associated polymorphisms and their non‐coding linkage disequilibrium (i.e., non‐randomly associated) partners. We identified 82 DNA variants of probable regulatory function that may contribute to autism pathogenesis. To validate these predictions, we measured the impact of 11 high‐confidence candidates and their GWAS linkage disequilibrium partners on gene expression in human brain tissue from Autistic and non‐Autistic donors. Although a small number of the surveyed variants exhibited measurable influence on gene expression as determined via quantitative polymerase chain reaction, these did not survive correction for multiple comparisons. Additionally, no significant genotype‐by‐diagnosis effects were observed for any of the SNP‐gene associations. We contend that this may reflect an inability to effectively capture the modest, neurodevelopmental‐specific impact of individual variants on biological dysregulation in available post‐mortem tissue samples, as well as limitations in the existing autism GWAS data. Lay Summary: Although researchers have identified genetic variants associated with autism, it is not well understood how exactly they contribute to the onset of the condition. This study examined whether a set of likely functional variants impacted on gene expression in human brain tissue from Autistic and non‐Autistic donors. We found that none of the variants were associated with changes in the amount of gene product expressed. This may reflect problems with the way researchers regularly predict and measure the biological function of genetic mutations. [ABSTRACT FROM AUTHOR]

Background: Despite the known benefits of accurate and timely diagnosis for children with attention-deficit hyperactivity disorder and autism spectrum disorders (autism), for some children this goal is not always achieved. Existing research has explored diagnostic delay for autism and attention-deficit hyperactivity disorder only, and when attention-deficit hyperactivity disorder and autism co-occur, autism has been the focus. No study has directly compared age at diagnosis and diagnostic delay for males and females across attention-deficit hyperactivity disorder, autism and specifically, attention-deficit hyperactivity disorder + autism. Methods: Australian caregivers (N = 677) of children with attention-deficit hyperactivity disorder, autism or attention-deficit hyperactivity disorder + autism were recruited via social media (n = 594) and the Monash Autism and ADHD Genetics and Neurodevelopment Project (n = 83). Caregivers reported on their child's diagnostic process. Diagnostic delay was the mean difference between general initial developmental concerns and the child's attention-deficit hyperactivity disorder and autism diagnosis. Results: Children with autism were significantly younger at autism diagnosis than the attention-deficit hyperactivity disorder + autism group (ηp2 = 0.06), whereas children with attention-deficit hyperactivity disorder were significantly older at attention-deficit hyperactivity disorder diagnosis than the attention-deficit hyperactivity disorder + autism group (ηp2 = 0.01). Delay to attention-deficit hyperactivity disorder and autism diagnosis was significantly longer in the attention-deficit hyperactivity disorder + autism group compared to attention-deficit hyperactivity disorder (ηp2 = 0.02) and autism (η2 = 0.04) only. Delay to autism diagnosis for females with autism (η2 = 0.06) and attention-deficit hyperactivity disorder + autism (η2 = 0.04) was longer compared to males. Conclusions: Having attention-deficit hyperactivity disorder + autism and being female were associated with longer delays to diagnosis. The reasons for these delays and possible adverse effects on outcomes require further study. [ABSTRACT FROM AUTHOR]

Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the willingness to engage in cognitively or physically effortful behavior. However, the degree to which effort sensitivity is impaired in ADHD has rarely been tested, and the efficacy of stimulant medication in ameliorating any such impairments is unclear. Here, we tested 20 individuals with ADHD (11 males, 9 females) who were managed with amphetamine-based medication (dexamfetamine, lisdexamfetamine), and 24 controls (8 males, 16 females). Individuals with ADHD were tested over two counterbalanced sessions, ON and OFF their usual amphetamine-based medication. In each session, participants performed an effortbased decision-making task, in which they were required to choose how much cognitive or physical effort they were willing to engage in return for reward. Our results revealed three main findings. First, individuals with ADHD had lower motivation relative to controls to invest effort in both the cognitive and physical domains. Second, amphetamine increased motivation uniformly across both domains. Finally, the net effect of amphetamine treatment was to mostly restore motivation across both domains of effort relative to healthy controls. These data provide clear evidence for a heightened sensitivity to both cognitive and physical effort in ADHD, and reveal the efficacy of amphetamine-based drugs in restoring effort sensitivity to levels similar to controls. These findings confirm the existence of reduced motivational drive in ADHD, and more broadly provide direct causal evidence for a domain-general role of catecholamines in motivating effortful behavior. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has markedly impacted functioning for children and adolescents including those with attention-deficit/hyperactivity disorder (ADHD). We explored home learning difficulties (HLD) during COVID-19 restrictions in Australian children (aged 5–17) with ADHD, aiming to: (1) describe home learning experiences, and (2) examine associations between child anxiety (i.e., concurrent anxiety symptoms and pre-existing anxiety disorder status) and HLD. Baseline data from the longitudinal ADHD COVID-19 Survey were used (n = 122). Parents reported on school factors and HLD; pre-existing anxiety and co-occurring difficulties; anxiety, ADHD, and oppositional symptoms; demographics; and medications. Parents retrospectively reported more children often looked forward to school pre-pandemic, than during the pandemic. Anxiety symptoms, but not pre-existing anxiety disorder status, were associated with HLD after accounting for covariates. ADHD inattention symptoms were also associated with HLD. Results support recommendations to continue pre-pandemic supports to assist with ADHD symptoms during home learning, and strategies/supports for families are discussed. [ABSTRACT FROM AUTHOR]

Objective: The Strengths and Difficulties Questionnaire is a widely used screening tool for emotional and behavioural problems in children. Recent quantitative analyses have raised concerns regarding its structural validity in Aboriginal and Torres Strait Islander communities. This paper aims to extend upon existing findings by analysing the factor structure of both the parent- and teacher-reported Strengths and Difficulties Questionnaire in this population across a broader age range than in previous studies. Methods: Participants were the caregivers and teachers of 1624 Aboriginal and Torres Strait Islander children (820 male, 804 female) aged 2–15 years from Waves 2–11 of the Longitudinal Study of Indigenous Children. The majority of children were Aboriginal living in major cities and inner regional areas. Internal consistency was estimated with McDonald's Omega. Exploratory structural equation modelling was conducted to investigate the factor structure of the parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire. Results: Responses from teachers demonstrated higher internal consistency than responses from parents, which was unacceptably low across most age groups. The purported five-factor structure of the Strengths and Difficulties Questionnaire failed to be replicated across both parent- and teacher-reported questionnaires. The results of bifactor and hierarchical exploratory structural equation models also failed to approximate the higher-order summary scales. These results indicate that the Strengths and Difficulties Questionnaire subscales and summary scores do not provide a valid index of emotional and behavioural problems in Aboriginal and Torres Strait Islander children. Conclusion: The Strengths and Difficulties Questionnaire should not be used with Aboriginal and Torres Strait Islander children. [ABSTRACT FROM AUTHOR]

Older adults exposed to enriched environments (EEs) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults (63% female, 37% male). Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain aging but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the aging brain. [ABSTRACT FROM AUTHOR]

Schizotypy is a multidimensional construct that captures a continuum of risk for developing schizophrenia-spectrum psychopathology. Existing 3-factor models of schizotypy, consisting of positive, negative, and disorganized dimensions have yielded mixed evidence of genetic continuity with schizophrenia using polygenic risk scores. Here, we propose an approach that involves splitting positive and negative schizotypy into more specific subdimensions that are phenotypically continuous with distinct positive symptoms and negative symptoms recognized in clinical schizophrenia. We used item response theory to derive high-precision estimates of psychometric schizotypy using 251 self-report items obtained from a non-clinical sample of 727 (424 females) adults. These subdimensions were organized hierarchically using structural equation modeling into 3 empirically independent higher-order dimensions enabling associations with polygenic risk for schizophrenia to be examined at different levels of phenotypic generality and specificity. Results revealed that polygenic risk for schizophrenia was associated with variance specific to delusional experiences (γ = 0.093, P =.001) and reduced social interest and engagement (γ = 0.076, P =.020), and these effects were not mediated via the higher-order general, positive, or negative schizotypy factors. We further fractionated general intellectual functioning into fluid and crystallized intelligence in 446 (246 females) participants that underwent onsite cognitive assessment. Polygenic risk scores explained 3.6% of the variance in crystallized intelligence. Our precision phenotyping approach could be used to enhance the etiologic signal in future genetic association studies and improve the detection and prevention of schizophrenia-spectrum psychopathology. [ABSTRACT FROM AUTHOR]