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Until recently, built environments have been designed exclusively to meet the needs of neurotypical populations; however, there is increasing recognition of the need to make built environments more accommodating for neurodiverse populations, including autistic individuals. This scoping review aims to comprehensively explore and synthesise this literature on the internal built environment for autistic individuals providing recommendations for designers, policymakers and clinicians. Five electronic databases were searched, resulting in a total of 28 studies being reviewed. Recommendations are provided for design and construction, lighting, sound, aesthetics, temperature and air quality. While in its early stages, evidence demonstrating the impact that particular qualities of light, colour, sound and spatial planning have on the human sensorium is emerging. In turn, this new knowledge is informing design decisions that are progressing interior environments towards inclusivity. Understanding the positive and negative impacts of decisions made in the design of the built environment has the potential to facilitate the participation and inclusion of autistic individuals.

Children with autism spectrum disorder (ASD) display difficulties with response to joint attention in natural settings but often perform comparably to typically developing (TD) children in experimental studies of gaze following. Previous work comparing infants at elevated likelihood for ASD versus TD infants has manipulated aspects of the gaze cueing stimulus (e.g. eyes only versus head and eyes together), but the role the peripheral object being attended to is not known. In this study of infants at elevated likelihood of ASD (N = 97) and TD infants (N = 29), we manipulated whether or not a target object was present in the cued area. Performance was assessed at 10, 14, and 18 months, and diagnostic assessment was conducted at age 3 years. The results showed that although infants with later ASD followed gaze to the same extent as TD infants in all conditions, they displayed faster latencies back to the model's face when (and only when) a peripheral object was absent. These subtle atypicalities in the gaze behaviors directly after gaze following may implicate a different appreciation of the communicative situation in infants with later ASD, despite their ostensively typical gaze following ability.

Autistic individuals experience higher rates of externalising and internalising symptoms that may vary with environmental factors. However, there is limited research on variation across settings that may highlight common factors with globally generalisable effects. Data were taken from two cohorts: a multinational European sample (n = 764; 453 autistic; 311 non-autistic; 6–30 years), and a South African sample (n = 100 non-autistic; 3–11 years). An exploratory factor analysis aggregated clinical (Verbal Comprehension and Perceptual Index), adaptive traits (Vineland Adaptive Behaviour Scale) and socio-economic variables (parental employment and education, home and family characteristics) in each cohort separately. With regression, we investigated the effect of these factors and autistic traits on internalising and externalising scores (measured with the Strengths and Difficulties Questionnaire). Cohorts showed similar four-factor structures (Person Characteristics, Family System, Parental and Material Resources). The 'Family System' factor captured family size and maternal factors and was associated with lower internalising and externalising symptoms in both cohorts. In the European cohort, high autistic traits reduced this effect; the opposite was found in the South Africa cohort. Our exploratory findings from two separate analyses represent consistent evidence that Family System is associated with internalising and externalising symptoms, with a context-specific impact in persons with high autism traits. Autistic individuals are more likely than non-autistic individuals to experience a mental health condition in their lifetime, and this includes externalising and internalising symptoms. We know very little about how different environments and family conditions impact these symptoms for autistic individuals. Improving our understanding of these relationships is important so that we can identify individuals who may be in greater need of support. In this article, we seek to improve our understanding of how environmental and family conditions impact externalising and internalising symptoms in autistic and non-autistic people. To do this, we conducted analyses with two cohorts in very different settings – in Europe and South Africa – to ensure our findings are globally representative. We used advanced statistical methods to establish environmental and family conditions that were similar to each other, and which could be combined into specific 'factors'. We found that four similar 'factors' could be identified in the two cohorts. These were distinguished by personal characteristics and environmental conditions of individuals, and were named Person Characteristics, Family System, Parental and Material Resources. Interestingly, just 'Family System' was associated with internalising and externalising symptoms, and this was the same in both cohorts. We also found that having high traits of autism impacted this relationship between Family System and mental health conditions with opposite directions in the two settings. These results show that characteristics in the Family System are associated with internalising and externalising symptoms, and autistic persons are particularly impacted, reinforcing the notion that family stressors are important to consider when implementing policy and practice related to improving the mental health of autistic people. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) are two often co-occurring neurodevelopmental conditions. Nevertheless, there is limited research about symptom differences between ASD and ASD + ADHD groups. This study examined differences in social interaction and communication between children and adolescents with ASD and with ASD + ADHD. A total of 112 participants were identified from two clinical trials. Fifty-six children and adolescents with ASD aged 8–17 years were matched for age, gender and general intelligence quotient with fifty-six children and adolescents with ASD + ADHD. Group differences in scores on the Autism Diagnostic Observation Schedule were analysed. Our results showed that participants with ASD and with ASD + ADHD had similar profiles of social communication interaction challenges and restricted behaviour. However, items assessing gestures: Conventional, Instrumental or Informational Gestures and Empathic or Emotional gestures showed significant differences between the groups suggesting that the ASD + ADHD group used descriptive gestures to communicate to a greater extent than the ASD group. These findings suggest that children and adolescents in both groups have similar difficulties in social communication and interaction with observed differences in the use of gestures. Possible reasons and implications for the differences in the use of gestures are discussed. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. Methods: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism–Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. Results: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (ra) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 0.30, 0.17, and 0.17, respectively). Limitations: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. Conclusions: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity. [ABSTRACT FROM AUTHOR]

Background: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. Aims: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. Method: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age). Results: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. Conclusions: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD. [ABSTRACT FROM AUTHOR]

Background: Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus–norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered LC-NE functioning contributes to different SSP and results in diverging social attention in ASD. Methods: We analyzed the baseline eye-tracking data of the EU-AIMS Longitudinal European Autism Project (LEAP) for subgroups of autistic participants (n = 166, age = 6–30 years, IQ = 61–138, gender [female/male] = 41/125) or neurotypical development (TD; n = 166, age = 6–30 years, IQ = 63–138, gender [female/male] = 49/117) that were matched for demographic variables and data quality. Participants watched brief movie scenes (k = 85) depicting humans in social situations (human) or without humans (non-human). SSP was estimated by gazes on physical and motion salience and a corresponding pupillary response that indexes phasic activity of the LC-NE. Social attention is estimated by gazes on faces via manual areas of interest definition. SSP is compared between groups and related to social attention by linear mixed models that consider temporal dynamics within scenes. Models are controlled for comorbid psychopathology, gaze behavior, and luminance. Results: We found no group differences in gazes on salience, whereas pupillary responses were associated with altered gazes on physical and motion salience. In ASD compared to TD, we observed pupillary responses that were higher for non-human scenes and lower for human scenes. In ASD, we observed lower gazes on faces across the duration of the scenes. Crucially, this different social attention was influenced by gazes on physical salience and moderated by pupillary responses. Limitations: The naturalistic study design precluded experimental manipulations and stimulus control, while effect sizes were small to moderate. Covariate effects of age and IQ indicate that the findings differ between age and developmental subgroups. Conclusions: Pupillary responses as a proxy of LC-NE phasic activity during visual attention are suggested to modulate sensory salience processing and contribute to attenuated social attention in ASD. [ABSTRACT FROM AUTHOR]

Introduction: Facial emotion recognition (FER) requires the integration of multi-dimensional information across various brain regions. Autistic individuals commonly experience difficulties in FER, a phenomenon often attributed to differences in brain connectivity. The nature of task-induced functional brain networks could provide insight into the neuromechanisms underlying FER difficulties in autism, however, to date, these mechanisms remain poorly understood. Methods: In this study, the task induced functional brain networks of 19 autistic and 19 gender, age, and IQ matched non-autistic individuals were examined during a complex FER task. Electroencephalogram (EEG)-based functional brain networks were examined, including the investigation of differences in the time-varying whole-brain functional networks and the exploration of the task induced small-world properties. Results: The results showed statistically significant differences in the task-induced functional networks between autistic and non-autistic adults. Autistic adults compared to non-autistic adults showed a significant shift in the connectivity-based FER processing from the lower to the higher EEG frequency bands. Discussion: These findings may provide evidence at a neural level for the notion that autistic individuals have a preference for bottom-up lower-level processing, or alterations in top-down global processing, potentially contributing to the FER difficulties observed in this population. Results also suggest that functional brain networks in autism show significantly altered task-induced whole-brain small-world properties as compared to non-autistic individuals during complex FER. This study motivates further investigation of the underlying networks-basis of altered emotion processing in autism. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioral, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterize heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with a varied array of cognitive tasks. Methods: All analyses were based on the EU-AIMS/AIMS-2-TRIALS multisite Longitudinal European Autism Project (LEAP) with participants with autism (n = 282) and typically developing (TD) controls (n = 221) between 6 and 30 years of age. We employed a novel task potency approach which combines the unique aspects of both resting state fMRI and task-fMRI to quantify task-induced variations in the functional connectome. Normative modelling was used to map atypicality of features on an individual basis with respect to their distribution in neurotypical control participants. We applied robust out-of-sample canonical correlation analysis (CCA) to relate connectome data to behavioral data. Results: Deviation from the normative ranges of global functional connectivity was greater for individuals with autism compared to TD in each fMRI task paradigm (all tasks p < 0.001). The similarity across individuals of the deviation pattern was significantly increased in autistic relative to TD individuals (p < 0.002). The CCA identified significant and robust brain-behavior covariation between functional connectivity atypicality and autism-related behavioral features. Conclusions: Individuals with autism engage with tasks in a globally atypical way, but the particular spatial pattern of this atypicality is nevertheless similar across tasks. Atypicalities in the tasks originate mostly from prefrontal cortex and default mode network regions, but also speech and auditory networks. We show how sophisticated modeling methods such as task potency and normative modeling can be used toward unravelling complex heterogeneous conditions like autism. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions develop during infancy, and current diagnostic protocols miss the age when therapy would be most effective. We developed non-invasive ASD biomarkers using mass spectrometry analyses of elemental metabolism in single hair strands, coupled with machine learning. We undertook a national prospective study in Japan, where hair samples were collected at 1 month and clinical diagnosis was undertaken at 4 years. Next, we analyzed a national sample of Swedish twins and, in our third study, participants from a specialist ASD center in the US. In a blinded analysis, a predictive algorithm detected ASD risk as early as 1 month with 96.4% sensitivity, 75.4% specificity, and 81.4% accuracy (n = 486; 175 cases). These findings emphasize that the dynamics in elemental metabolism are systemically dysregulated in autism, and these signatures can be detected and leveraged in hair samples to predict the emergence of ASD as early as 1 month of age. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder (ASD) display difficulties with response to joint attention in natural settings but often perform comparably to typically developing (TD) children in experimental studies of gaze following. Previous work comparing infants at elevated likelihood for ASD versus TD infants has manipulated aspects of the gaze cueing stimulus (e.g. eyes only versus head and eyes together), but the role the peripheral object being attended to is not known. In this study of infants at elevated likelihood of ASD (N = 97) and TD infants (N = 29), we manipulated whether or not a target object was present in the cued area. Performance was assessed at 10, 14, and 18 months, and diagnostic assessment was conducted at age 3 years. The results showed that although infants with later ASD followed gaze to the same extent as TD infants in all conditions, they displayed faster latencies back to the model's face when (and only when) a peripheral object was absent. These subtle atypicalities in the gaze behaviors directly after gaze following may implicate a different appreciation of the communicative situation in infants with later ASD, despite their ostensively typical gaze following ability. During the first year of life, infants start to align their attention with that of other people. This ability is called joint attention and facilitates social learning and language development. Although children with autism spectrum disorder (ASD) are known to engage less in joint attention compared to other children, several experimental studies have shown that they follow other's gaze (a requirement for visual joint attention) to the same extent as other children. In this study, infants' eye movements were measured at age 10, 14, and 18 months while watching another person look in a certain direction. A target object was either present or absent in the direction of the other person's gaze. Some of the infants were at elevated likelihood of ASD, due to having an older autistic sibling. At age 3 years, infants were assessed for a diagnosis of ASD. Results showed that infants who met diagnostic criteria at 3 years followed gaze to the same extent as other infants. However, they then looked back at the model faster than typically developing infants when no target object was present. When a target object was present, there was no difference between groups. These results may be in line with the view that directly after gaze following, infants with later ASD are less influenced by other people's gaze when processing the common attentional focus. The study adds to our understanding of both the similarities and differences in looking behaviors between infants who later receive an ASD diagnosis and other infants. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication, but also great heterogeneity. To offer individualized medicine approaches, we need to better target interventions by stratifying autistic people into subgroups with different biological profiles and/or prognoses. We sought to validate neural responses to faces as a potential stratification factor in ASD by measuring neural (electroencephalography) responses to faces (critical in social interaction) in N = 436 children and adults with and without ASD. The speed of early-stage face processing (N170 latency) was on average slower in ASD than in age-matched controls. In addition, N170 latency was associated with responses to faces in the fusiform gyrus, measured with functional magnetic resonance imaging, and polygenic scores for ASD. Within the ASD group, N170 latency predicted change in adaptive socialization skills over an 18-month follow-up period; data-driven clustering identified a subgroup with slower brain responses and poor social prognosis. Use of a distributional data-driven cutoff was associated with predicted improvements of power in simulated clinical trials targeting social functioning. Together, the data provide converging evidence for the utility of the N170 as a stratification factor to identify biologically and prognostically defined subgroups in ASD. Exploiting face processing in patients with ASD: The heterogeneity observed in patients with autism spectrum disorder (ASD) highlights the need for better patient stratification methods. Here, Mason et al. evaluated the use of the speed of early-stage face processing (N170 latency) for clinical stratification and prognosis in ASD and age-matched healthy individuals. N170 latency was slower in individuals with ASD and correlated with response to faces measured with fMRI and with polygenic risk score. Among participants with ASD, the N170 values stratified patients according to socialization prognosis and improved power in a simulated clinical trial. The results suggest that including N170 evaluation in clinical stratification might help the design and development of patient-specific therapies for ASD. [ABSTRACT FROM AUTHOR]

Background: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. Methods: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2–32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%–30% split). Results: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p =.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52–0.62, specificity 0.59–0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. Limitations: The statistical power to detect weak effects—of the magnitude of those found in the training dataset—in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. Conclusions: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. [ABSTRACT FROM AUTHOR]

Content validity describes the extent to which a measure represents, and is relevant to, the construct it aims to assess. The International Classification of Functioning, Disability and Health and derived Core/Code Sets (Sets) for autism, attention deficit-hyperactivity disorder, cerebral palsy and early developmental delay and disability are adequate to establish the content validity of measures aiming to assess functioning in young children with neurodevelopmental conditions (NDCs). This article aimed to assess the content validity of comprehensive assessments of functioning for young children with NDCs against these standards. Twenty-two common measures of functioning were evaluated for content validity against the International Classification of Functioning, Disability and Health at a domain level, with 10 measures analysed at the item-level and compared to the Sets relevant to young children with NDCs. Measures covered between 21% and 57% of the combined Set codes and 19% to 63% of codes from specific Sets. Much of this variation was between measures, with some variation due to differences between individual Sets. The percentages reflect that measures heavily focus on activities and participation areas, with environmental factors rarely assessed. These findings are useful for clinicians, policymakers, and researchers in identifying the most appropriate measures for assessing functioning in young children with neurodevelopmental conditions. Young children who have developmental delay, autism, or other neurodevelopmental conditions can have difficulties doing things in different areas of their life. What they can and cannot do is called their level of functioning. There are lots of assessment measures that aim to assess functioning. But, we are not sure if these measures assess all the things we need to know about these children's functioning. Other research has identified lists of items (codes) that need to be assessed to understand functioning for young children with different neurodevelopmental conditions fully. These lists include body functions (the things a child's body or brain can do), activities and participation (the activities and tasks a child does) and environmental factors (parts of the environment that can influence functioning). In this study, we looked at the items from these lists assessed by different functioning measures to see how they compared to what should be assessed. The measures that we looked at covered 21%–57% of all the codes and 19%–63% of the codes for lists specific to different conditions. Most of the measures focused on activity and participation codes, and they rarely assessed environmental factors. Knowing which codes and how much of the lists the measures assess can help researchers, clinicians and policymakers to choose measures that are more appropriate for young children with neurodevelopmental conditions. [ABSTRACT FROM AUTHOR]

Background: A significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs. Methods: A monozygotic co-twin design was applied in a sample of 224 twins (mean age = 17.70 years, SD = 6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes. Results: Birth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load. Limitations: When exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs. Conclusions: The findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions. [ABSTRACT FROM AUTHOR]

Previous research indicates elevated levels of clinically significant traits and symptoms of autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD) in children with chronic pain, but associations with functioning and depression are yet unclear. The current study examined the relationships of autistic traits and ADHD symptoms with pain interference, depression, and health-related quality of life, as well as the mediating roles of insomnia and psychological inflexibility, in children with chronic pain (n = 146, 8–17 years, 102 girls) presenting at a tertiary pain clinic. Children completed measures of pain intensity, depression, pain interference, health-related quality of life, insomnia, and psychological inflexibility. Parents (n = 146, 111 mothers) completed measures to assess autistic traits and ADHD symptoms in their children. Children with clinically significant autistic traits and ADHD symptoms presented with significantly higher levels of depressive symptoms and pain interference, and significantly lower health-related quality of life, than did the other children. Autistic traits and ADHD symptoms contributed significantly to the prediction of pain interference and depressive symptoms, as well as health-related quality of life. Psychological inflexibility mediated the relationships between ADHD symptoms and autistic traits on the one hand and depression, pain interference, and health-related quality of life on the other, while insomnia mediated the relationships between ADHD symptoms and depression, pain interference, and health-related quality of life. All analyses were adjusted for demographics and pain intensity. Results suggest the utility of screening for neurodevelopmental disorders in children with chronic pain. Furthermore, the findings may indicate insomnia and skills related to psychological flexibility as potential treatment targets in interventions aiming at improving functioning and health-related quality of life in children with chronic pain and co-occurring symptoms of neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

While neurodevelopmental disorders (NDDs) are highly heritable, several environmental risk factors have also been suggested. However, the role of familial confounding is unclear. To shed more light on this, we reviewed the evidence from twin and sibling studies. A systematic review was performed on case control and cohort studies including a twin or sibling within-pair comparison of neurodevelopmental outcomes, with environmental exposures until the sixth birthday. From 7,315 screened abstracts, 140 eligible articles were identified. After adjustment for familial confounding advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress were associated with autism spectrum disorder (ASD), and low birth weight, gestational age and family income were associated with attention-deficit/hyperactivity disorder (ADHD), categorically and dimensionally. Several previously suspected factors, including pregnancy-related factors, were deemed due to familial confounding. Most studies were conducted in North America and Scandinavia, pointing to a global research bias. Moreover, most studies focused on ASD and ADHD. This genetically informed review showed evidence for a range of environmental factors of potential casual significance in NDDs, but also points to a critical need of more genetically informed studies of good quality in the quest of the environmental causes of NDDs. [ABSTRACT FROM AUTHOR]

No robust biomarkers have yet been identified for autism spectrum disorder (ASD) or autistic traits. Familial factors likely influence biomarkers such as protein concentrations. Comparing twins with ASD or high autistic traits to the less affected co‐twin allows estimating the impact of familial confounding. We measured 203 proteins in cerebrospinal fluid (n = 86) and serum (n = 127) in twins (mean age 14.2 years, 44.9% females) enriched for ASD and other neurodevelopmental conditions. Autistic traits were assessed by using the parent‐report version of the Social Responsiveness Scale‐2. In cerebrospinal fluid, autistic traits correlated negatively with three proteins and positively with one. In serum, autistic traits correlated positively with 15 and negatively with one. Also in serum, six were positively—and one negatively—associated with ASD. A pathway analysis of these proteins revealed immune system enrichment. In within twin pair analyses, autistic traits were associated with serum B‐cell activating factor (BAFF) only, whereas Cystatin B (CSTB) remained significantly associated with ASD. These associations did not remain significant when only considering monozygotic twins. For the remainder, the within‐pair analysis indicated familial confounding, including shared environment and genes, influencing both autism and protein levels. Our findings indicate proteins involved in immunity as putative biomarkers of autistic traits and ASD with partial genetic confounding. Although some results are in line with previous studies in general, further studies are needed for replication. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder is associated with sensory processing alterations, such as sensory hyper- and hypo-responsiveness. Twin studies are scarce in this field, but they are necessary in order to disentangle the genetic and environmental contributions to this association. Furthermore, it is unclear how different neurodevelopmental/psychiatric conditions contribute to altering sensory processing. We investigated the association between autistic traits/autism spectrum disorder diagnosis and sensory processing alterations in twins (N = 269), using the adult/adolescent sensory profile, which differentiates four sub-domains: Low Registration, Sensation Seeking, Sensory Sensitivity, and Sensation Avoiding. While the associations between autistic traits and Low Registration and Sensation Avoiding persisted within monozygotic (genetically identical) twins, Sensory Sensitivity was only associated with autistic traits within dizygotic twins. In multivariate analyses with different neurodevelopmental/psychiatric diagnoses as predictor variables, autism spectrum disorder and attention deficit hyperactivity disorder were the strongest predictors for two adult/adolescent sensory profile sub-domains each. The results suggest that the association between autistic traits and Sensory Sensitivity is influenced by genetics while non-shared environmental factors influence the associations between autistic traits and Low Registration and Sensation Avoiding. They further indicate that altered sensory processing is not specific to autism spectrum disorder, while autism spectrum disorder is a strong predictor of certain sensory processing alterations, even when controlling for other (comorbid) neurodevelopmental/psychiatric conditions. Individuals diagnosed with autism often describe that they process sensory information differently from others, and many experience sensory issues as problematic. For instance, an increased sensitivity to smells or sounds can make participating in social settings challenging. While sensory issues are now part of the diagnostic criteria for autism, they also co-occur with other psychiatric diagnoses such as attention deficit hyperactivity disorder and anxiety disorders. It is unclear to what extent the relationship between autism and alterations in sensory processing are due to genetics or environment. In addition, more research is needed on how autism, as compared to other diagnoses, is associated with sensory issues. Using a twin study, we found that genetic factors influenced self-reported reactivity to sensory stimuli in autism while environmental factors influenced other sensory issues (e.g. difficulties in detecting or differentiating sensory input). Hence, sensory hyper-reactivity might be an early onset core feature of autism, while other domains of alterations in sensory processing might develop later, influenced by the environment. Moreover, autism was more strongly associated with sensory issues related to increased sensitivity/reactivity as compared to other psychiatric diagnoses. However, attention deficit hyperactivity disorder was more strongly related to deficits in detecting/differentiating sensory stimuli and with an increased drive to seek sensory input. Our results indicate that sensory issues are not specific to autism, but that some aspects of altered sensory processing are more relevant for autism than for other diagnoses. [ABSTRACT FROM AUTHOR]

Altered resting-state functional connectivity in the default mode network (DMN) is characteristic of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Standard analytical pipelines for resting-state functional connectivity focus on linear correlations in activation time courses between neural networks or regions of interest. These features may be insensitive to temporally lagged or nonlinear relationships. In a twin cohort study comprising 292 children, including 52 with a diagnosis of ASD and 70 with a diagnosis of ADHD, we applied nonlinear analytical methods to characterize periodic dynamics in the DMN. Using recurrence quantification analysis and related methods, we measured the prevalence, duration, and complexity of periodic processes within and between DMN regions of interest. We constructed generalized estimating equations to compare these features between neurotypical children and children with ASD and/or ADHD while controlling for familial relationships, and we leveraged machine learning algorithms to construct models predictive of ASD or ADHD diagnosis. In within-pair analyses of twins with discordant ASD diagnoses, we found that DMN signal dynamics were significantly different in dizygotic twins but not in monozygotic twins. Considering our full sample, we found that these patterns allowed a robust predictive classification of both ASD (81.0% accuracy; area under the curve = 0.85) and ADHD (82% accuracy; area under the curve = 0.87) cases. These findings indicate that synchronized periodicity among regions comprising the DMN relates both to neurotypical function and to ASD and/or ADHD, and they suggest generally that a dynamical analysis of network interconnectivity may be a useful methodology for future neuroimaging studies. [ABSTRACT FROM AUTHOR]