Search

Background: While hypertension is a modifiable risk factor of Alzheimer's disease and related dementias (ADRD), limited studies have been conducted on the effectiveness of antihypertensive medications (AHMs) in altering the progression from mild cognitive impairment (MCI) to ADRD; similarly, few studies have assessed drug-drug interactions of AHMs with drugs targeted to modify other risk factors of ADRD such as type Ⅱ diabetes and hypercholesterolemia. Method: 128,683 unique hypertensive patients with MCI on US-based Optum claims data were identified. Diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor antagonists (ARBs) were identified as five major AHM classes. Baseline characteristics were compared. Cox proportional hazards (PH) models were used to study the association between specific AHM exposure and the progression from MCI to ADRD while controlling for demographic variables, comorbidities, and the use of Statins and Metformin. To examine the association of AHM-Statin or AHM-Metformin interaction with ADRD progression, we also investigated models controlling for the aforementioned confounders, as well as drug-drug interactions. Result: The study included 100,678 patients who were taking at least one class of AHM and 28,005 who were not taking any AHMs during the study period. AHM users had a higher incidence of comorbidities (all P≤0.039) and consumption of Metformin and Statins (both PConclusion: All five major AHM classes showed a protective effect against ADRD progression among hypertensive patients with MCI. Also, certain combinations of AHMs with Metformin or Statins showed a stronger protective effect compared to AHMs alone, and some drug-drug interactions of AHMMetformin or AHM-Statin also showed protective effects against progression from MCI to ADRD.

Given that camouflaging has been suggested to contribute to delayed diagnosis and mental health problems among autistic people, validated measures of the construct are needed. This study describes the psychometric evaluation of the Swedish adaptation of the self-reported Camouflaging Autistic Traits Questionnaire (CAT-Q) in autistic (n = 100) and general population (n = 539) samples aged 10 to 83 years. Analyses indicated good-to-excellent internal consistency and test-retest reliability. Construct validity was supported by autistic participants scoring higher than non-autistic, and autistic females scoring higher than autistic males on the measure. Also as expected, camouflaging was associated with theoretically linked traits, including autistic behaviors and depressive symptoms. On the other hand, the factor structure of the original CAT-Q did not provide a good fit in the Swedish data set, and validity issues were found, particularly in children younger than 15 years, warranting further investigation of the construct validity of the scale. Different age trajectories were observed, where camouflaging behaviors decreased during adulthood in non-autistic people but remained at an elevated level among autistic people.

Autism is a neurodevelopmental condition associated with atypical social communication, cognitive, and sensory faculties. Recent advances in exposure biology suggest that biomarkers of elemental uptake and metabolism measured in hair samples can yield an effective signal predictive of autism diagnosis. Here, we investigated if elemental biomarkers in hair were associated with functional connectivity in regions of the default mode network (DMN) previously linked to autism. In a study sample which included twin pairs with concordant and discordant diagnoses for autism, our analysis of hair samples and neuroimaging data supported two general findings. First, independent of autism diagnosis, we found a broad pattern of association between elemental biomarkers and functional connectivity in the DMN, which primarily involved dynamics in zinc metabolism. Second, we found that associations between the DMN and elemental biomarkers, particularly involving phosphorus, calcium, manganese, and magnesium, differed significantly in autistic participants from control participants. In sum, these findings suggest that functional dynamics in elemental metabolism relate broadly to persistent patterns of functional connectivity in the DMN, and that these associations are altered in the emergence of autism.

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.

Atypical sensory processing is prevalent across neurodevelopmental conditions and a key diagnostic criterion of autism spectrum disorder. It may have cascading effects on the development of adaptive functions. However, its unique contribution to adaptive functioning and the genetic/environmental influences on this link are unclear. In a clinically enriched twin sample ( n = 289, 60 diagnosed with autism spectrum disorder), we investigated the associations between the quadrants of the Adult/Adolescent Sensory Profile (low registration, sensory sensitivity, sensation seeking, and sensation avoiding) and adaptive functioning. Associations were modeled across the cohort accounting for the effects of clinical diagnosis, IQ, sex and age, and within-twin pairs, additionally implicitly adjusting for familial factors. Furthermore, we explored interaction effects between atypical sensory processing and autism spectrum disorder diagnosis. Sensory sensitivity and sensation avoiding were associated with reduced adaptive functioning across individuals, but not within-twin pairs. An interaction effect was found between sensation seeking and autism spectrum disorder diagnosis, showing a negative association between sensation seeking and adaptive functioning only in individuals diagnosed with autism spectrum disorder. The results suggest that atypical sensory processing is associated with reduced adaptive functioning and that familial factors influence this link. In addition, sensation seeking behaviors might interfere with adaptive functioning specifically in individuals with autism spectrum disorder. Lay abstract Individuals diagnosed with autism tend to process sensory information differently than individuals without autism, resulting for instance in increased sensitivity to sounds or smells. This leads to challenges in everyday life and may restrict the individual’s daily functioning. How direct this link is, however, is currently unclear. We investigated this question in 289 twins of whom 60 were diagnosed with autism and further 61 were diagnosed with other neurodevelopmental disorders. We looked at the association between unusual sensory processing and adaptive skills, both across individuals and within-twin pairs, testing whether individuals with higher levels of atypical sensory processing showed reduced adaptive skills compared to their twins. Since twins share 50%–100% of their genes and part of their environment (e.g. family background), associations within-twin pairs are free from effects of these familial factors. We found that an increased sensitivity to, as well as the avoiding of, sensory input (hyper-responsiveness) was linked to reduced adaptive skills across individuals—but not within-twin pairs. We also found an association between the degree to which individuals seek for sensory input (sensation seeking) and reduced adaptive skills, but only in individuals diagnosed with autism. The results suggest that sensory hyper-responsiveness has negative effects on individuals’ general ability to function, but that this link is influenced by familial factors and hence not direct. In addition, sensation seeking behaviors might have a negative impact on adaptive skills specifically in autistic individuals.

Genetic variants affectingHeterogeneous Nuclear Ribonucleoprotein U (HNRNPU)have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role ofHNRNPUin cerebral cortical development, but the effects ofHNRNPUdeficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes ofHNRNPUlocus deficiency duringin vitroneural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate thatHNRNPUdeficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level.HNRNPUdownregulation leads to altered neurogenesis and an increased fraction of neural progenitors in the maturing neuronal population. We conclude that,HNRNPUlocus is involved in delayed commitment of neural progenitors to neuronal maturation in cell types with hindbrain profile.

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. Lay abstract 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.

Few studies have addressed gender differences in autism in relation to functioning and across cultures. We aimed to explore functional gender differences in autism from a multidisciplinary, global perspective using the International Classification of Functioning, Disability, and Health. Perceptions among professionals in high-income countries and middle-income countries were examined based on qualitative survey data from N = 225 professionals. Of these, n = 131 professionals provided information on functional gender differences in autism. Thirty-two professionals reported perceiving no gender differences. Remaining respondents ( n = 99)—representing 31 countries, all World Health Organization regions, and 10 different professions—were included in a content analysis on functional gender differences, which generated three main categories and 13 subcategories. The subcategories were subsequently linked to International Classification of Functioning, Disability, and Health categories. Autistic males were described as displaying more externalizing behaviors, and females as having more internalizing problems and being more socially motivated. Thirty-two International Classification of Functioning, Disability, and Health categories were identified, of which 31 were covered by the comprehensive Core Set for autism. Gender differences in core symptoms and co-existing problems were acknowledged by professionals from both high-income countries and middle-income countries, while differences in social behaviors, including camouflaging, were more frequently described by experts from high-income countries. Lay abstract In this study, we explored if professionals working with autistic people in different regions of the world perceive differences between females and males diagnosed with the condition. A total of 131 professionals responded to a survey that included an open question about gender differences in autism. Of these, 32 responded that they do not perceive gender differences in autism. The information provided by the other 99 experts was analyzed to identify common patterns. Three main differences were found, (1) Matching the clinical conceptualization of autism where professionals described differences in core symptoms of autism, and that autistic females were less similar to the conceptualization of autism. In (2) Co-existing problems, professionals described that autistic males display more apparent problems including hyperactivity, while autistic females were perceived as having more internalizing issues such as anxiety and eating disorders. In the last category, (3) Navigating the social environment, experts perceived autistic females as more socially motivated, and more inclined to camouflage social difficulties, making their challenges less evident. Professionals also perceived differences in the social environment, for example, that autistic girls receive more support from their peers while autistic boys are more often bullied. Our results suggest that professionals working in different parts of the world acknowledge gender differences in autism, but also that there might be some regional differences. Finally, we found that gender differences reported by the international professionals could largely be assessed with a shortened version of the International Classification of Functioning by the World Health Organization, specifically developed for autism.

Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

BackgroundA 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.MethodsA 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.ResultsBirth 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.LimitationsWhen 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.ConclusionsThe 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.

Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79–6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57–2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2–5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62–9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66–7.15) to OR 7.36 (1.99–27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.

This study investigated the association between autism and self-reported eating problems and the influence of gender on the association, in a sample of adolescent and adult twins (N = 192). Autistic traits and autism diagnosis were associated with both total and specific eating problems, including selective eating and sensory sensitivity during mealtimes. Interaction effects indicated a stronger association between autistic traits and total eating problems in females, as well as more difficulties with eating in social contexts among autistic females. In within-pair analyses, where unmeasured confounders including genes and shared environment are implicitly controlled for, the association was lost within monozygotic pairs, which might further indicate a genetic influence on the relationship between autism and eating problems.

Background Non‐shared environment (NSE) effects account for around one‐third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce. Methods A systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co‐twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle–Ottawa Scale. Results Twenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health‐related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible. Conclusions Our results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co‐occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls. Although these alterations affect multiple and widespread cortical regional asymmetries, the extent to which specific structural networks might be affected remains unknown. Inter-regional morphological covariance analysis can capture network connectivity relations between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1,455 individuals with ASD and 1,560 controls, across 43 independent datasets of the ENIGMA consortium’s ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered asymmetry of hemispheric networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, driven by shifts toward higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve working memory, executive functions, language, reading, and sensorimotor processes. Taken together, these findings provide new insights into how altered brain left-right asymmetry in ASD affects specific structural and functional brain networks. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Alterations in social cognition are hypothesized to underlie social communication challenges in autism spectrum disorder. However, the etiologic underpinnings driving this association, as well as the impact of other psychiatric conditions on the association, remain unclear. Using a co-twin control design, we examined n = 308 twins (mean age = 16.63; 46% females) with autism spectrum disorder, attention-deficit/hyperactivity disorder, affective disorders, or typical development using the Reading the Mind in the Eyes Test to operationalize social cognition ability. Clinical diagnosis of autism spectrum disorder, as well as the extent of quantitative autistic traits, as measured by parental reports using the Social Responsiveness Scale-2, predicted fewer expected responses on the Reading the Mind in the Eyes Test across the pairs. The association remained when adjusting for other diagnoses and IQ. In addition, male sex, lower age, and lower IQ predicted poorer performance on the Reading the Mind in the Eyes Test. The associations between autism and social cognition ability were lost within pairs in both the full sample and the monozygotic subsample. We conclude that the association between autism and social cognition across the sample highlights the importance of social cognition alterations in autism spectrum disorder when compared with other conditions. The attenuation of the association in the within-pair models indicate familial confounding, such as genes and shared environment, influencing both autism and social cognition.

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.

Supplemental material, sj-pdf-1-aut-10.1177_1362361321991255 for A co-twin-control study of altered sensory processing in autism by Janina Neufeld, Mark J Taylor, Karl Lundin Remnélius Taylor, Johan Isaksson, Paul Lichtenstein and Sven Bölte in Autism

While previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8–36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00–1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03–1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

Background Autism Spectrum Disorder (ASD) is associated with altered global and local visual processing. However, the nature of these alterations remains controversial, with contradictory findings and notions ranging from a reduced drive to integrate information into a coherent 'gestalt' ("weak central coherence" = WCC) to an enhanced perceptual functioning (EPF) in local processing. Methods This study assessed the association between autism and global/local visual processing, using a large sample of monozygotic (MZ) and dizygotic (DZ) twins (N = 290, 48% females, age = 8-31 years). The Fragmented Pictures Test (FPT) assessed global processing, whereas local processing was estimated with the Embedded Figures Test (EFT) and the Block Design Test (BDT). Autism was assessed both categorically (clinical diagnosis), and dimensionally (autistic traits). Associations between visual tasks and autism were estimated both across the cohort and within-twin pairs where all factors shared between twins are implicitly controlled. Results Clinical diagnosis and autistic traits predicted a need for more visual information for gestalt processing in the FPT across the cohort. For clinical diagnosis, this association remained within-pairs and at trend-level even within MZ twin pairs alone. ASD and higher autistic traits predicted lower EFT and BDT performance across the cohort, but these associations were lost within-pairs. Conclusions In line with the WCC account, our findings indicate an association between autism and reduced global visual processing in children, adolescents and young adults (but no evidence for EPF). Observing a similar association within MZ twins suggests a non-shared environmental contribution.

Physical examinations are recommended as part of a comprehensive evaluation for individuals with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder. These examinations should include assessment for morphological variants. Previous studies have shown an increase in morphological variants in individuals with NDDs, particularly ASD, and that these variants may be present in greater amounts in individuals with genetic alterations. Unfortunately, assessment for morphological variants can be subjective and time-consuming, and require a high degree of clinical expertise. Therefore, objective, automated methods of morphological assessment are desirable. This study compared the use of Face2Gene, an automated tool to explore facial morphological variants, to clinical consensus assessment, using a cohort of N = 290 twins enriched for NDDs (n = 135 with NDD diagnoses). Agreement between automated and clinical assessments were satisfactory to complete (78.3-100%). In our twin sample, individuals with NDDs did not have greater numbers of facial morphological variants when compared to those with typical development, nor when controlling for shared genetic and environmental factors within twin pairs. Common facial morphological variants in those with and without NDDs were similar and included thick upper lip vermilion, abnormality of the nasal tip, long face, and upslanted palpebral fissure. We conclude that although facial morphological variants can be assessed reliably in NDDs with automated tools like Face2Gene, clinical utility is limited when just exploring the facial region. Therefore, currently, automated assessments may best complement, rather than replace, in-person clinical assessments.

Alterations in social cognition (SC) are hypothesized to underlie social communication and interaction challenges in autism spectrum disorder (ASD). The aetiological underpinnings driving this association remain unclear. We examined SC in 196 twins with ASD, other neurodevelopmental disorders or typical development using the naturalistic Movie for the Assessment of Social Cognition. Autism and its severity were assessed with the Autism Diagnostic Observation Schedule-2, and autistic traits with the Social Responsiveness Scale-2. Using within twin-pair regression models, controlling for age, sex, IQ, and unmeasured familial confounders such as genetic background and shared-environment, SC correlated with ASD diagnosis, autism severity, and autistic traits. Our findings highlight the importance of SC alterations in autism and suggest a non-shared environmental impact on the association. Electronic supplementary material The online version of this article (10.1007/s10803-019-04001-4) contains supplementary material, which is available to authorized users.