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The sex bias in autism diagnosis suggests the involvement of sex-specific endocrine mechanisms during prenatal development, but these hormones affect health throughout life. Therefore, the current study examined the association of autism and autistic traits with conditions and symptoms related to the sex-steroid system in adult women. In total, 1230 women (361 autistic), aged 15–77 years, reported on autistic traits and medical history. Medical diagnoses and symptoms were grouped by unsupervised factor analysis, and associations with autism diagnosis and autistic traits were explored. Higher rates of reproductive system diagnoses (odds ratio = 1.035, p = 0.024), prediabetes symptoms (odds ratio = 1.319, p = 0.001), irregular puberty onset (odds ratio = 1.458, p = 0.009), and menstrual length (odds ratio = 1.368, p = 0.034) and lower rates of metabolic and vascular conditions (odds ratio = 0.654, p = 0.013) were associated with diagnosis. Reproductive system diagnoses (β = 0.114, p = 0.000), prediabetes symptoms (β = 0.188, p = 0.000), menstrual length (β = 0.071, p = 0.014), irregular puberty onset (β = 0.149, p = 0.000), excessive menstruation symptoms (β = 0.097, p = 0.003), and hyperandrogenism symptoms (β = 0.062, p = 0.040) were also associated with autistic traits. Many of the conditions and symptoms found to be associated with autism or autistic traits are also related to conditions of steroid hormones and, specifically, the sex-steroid system. The study suggests an important role for steroids in autistic women, beyond prenatal development. Clinical implications are discussed. Lay abstract Sex-steroids, such as testosterone, are thought to be one of the biological factors implicated in autism. This relies on the sex bias in the diagnosis of autism (boys are approximately four times more likely to be diagnosed than girls) and findings of associations with fetal testosterone levels in traits and abilities related to autism. The current study aimed to examine the association between medical conditions and physical symptoms, which tend to manifest in adulthood, and autism in females. Moreover, we examined their association with autistic traits throughout the spectrum. We focused on autistic women because there is little research focusing on the healthcare needs of autistic women, but those that exist suggest heightened vulnerability, and lower access to medical care. We find that conditions related to steroid hormones function are more frequent in autistic women and that they correlate with autistic traits. Specifically, we found that body mass index, reproductive system diagnoses, prediabetes symptoms, irregular puberty onset, and menstrual irregularities were significantly more frequent in autistic women and were significantly correlated with autistic traits in neurotypical women. The findings have important implications for raising awareness in autistic women of the possibility of medical conditions which might need medical attention. In addition, healthcare providers should consider these associations when performing healthcare maintenance checks and/or screening for autism.

Background. While genetics is clearly implicated in the etiology of autism, other biological factors may also increase the likelihood of an autism diagnosis. Many of these pertain to obstetric history and maternal medical conditions, but as they tend to co-occur it is difficult to ascertain which ones are most predictive of child's autism.Methods. Women reported regarding their medical history and the pregnancy history of their first-born (N=557, 34.5% of children diagnosed with autism) and second-born (N=374, 28.1% of children diagnosed with autism) children. In Study 1, the first-born and second-born data were analyzed separately using LASSO, which enables the selection of variables most associated with child's autism. In Study 2, obstetric course and perinatal factors were compared for siblings discordant for autism (N mothers= 132, 61.7% males), thus allowing to control for many genetic and environmental aspects. Results. Study 1 revealed maternal medical conditions, obstetric course factors, and perinatal factors predictive of child's autism (15 and 20 predictors for the first and second child analyses, respectively). Factors that replicated across the two pregnancies were among others, infertility, vaginal bleeding during pregnancy, and Type II diabetes. Study 2 revealed that maternal vaginal bleeding differentiated the pregnancy course of children later diagnosed with autism from neurotypical children.Limitations. The medical information analyzed in this study is based on participants' recollection. While this approach allows to collect information regarding medical symptoms that may not have been logged in official medical records, participants might have forgotten relevant information. Future studies would benefit from combining self-report and health-provider recorded data. Conclusions. This is one of few studies to analyze a large set of predictors, spanning maternal medical conditions, obstetric course, and perinatal factors. Analyzing these together, using machine-learning methods, allows us to disentangle the specific factors associated with child's autism. Study 2 enabled us to examine this within families, thus passively controlling for genetic and non-specific environmental effects. Our findings highlight the pregnancy course and maternal fertility factors which are of importance for predicting child's autism.

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multicenter structural magnetic resonance imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male), and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. Increases were observed in different brain regions in males and females, with larger effect sizes in females. BSC correlated with ADOS-2 Calibrated Severity Score in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared with cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

BackgroundThe global COVID-19 pandemic has had an unprecedented impact on European health and social care systems, with demands on testing, hospital and intensive care capacity exceeding available resources in many regions. This has led to concerns that some vulnerable groups, including autistic people, may be excluded from services.MethodsWe reviewed policies from 15 European member states, published in March–July 2020, pertaining to (1) access to COVID-19 tests; (2) provisions for treatment, hospitalisation and intensive care units (ICUs); and (3) changes to standard health and social care. In parallel, we analysed survey data on the lived experiences of 1301 autistic people and caregivers.ResultsAutistic people experienced significant barriers when accessing COVID-19 services. First, despite being at elevated risk of severe illness due to co-occurring health conditions, there was a lack of accessibility of COVID-19 testing. Second, many COVID-19 outpatient and inpatient treatment services were reported to be inaccessible, predominantly resulting from individual differences in communication needs. Third, ICU triage protocols in many European countries (directly or indirectly) resulted in discriminatory exclusion from lifesaving treatments. Finally, interruptions to standard health and social care left over 70% of autistic people without everyday support.ConclusionsThe COVID-19 pandemic has further exacerbated existing healthcare inequalities for autistic people, probably contributing to disproportionate increases in morbidity and mortality, mental health and behavioural difficulties, and reduced quality of life. An urgent need exists for policies and guidelines on accessibility of COVID-19 services to be updated to prevent the widespread exclusion of autistic people from services, which represents a violation of international human rights law.

Autism spectrum disorder (ASD) is associated with atypical brain development. However, the phenotype of regionally specific increased cortical thickness observed in ASD may be driven by several independent biological processes that influence the gray/white matter boundary, such as synaptic pruning, myelination, or atypical migration. Here, we propose to use the boundary sharpness coefficient (BSC), a proxy for alterations in microstructure at the cortical gray/white matter boundary, to investigate brain differences in individuals with ASD, including factors that may influence ASD-related heterogeneity (age, sex, and intelligence quotient). Using a vertex-based meta-analysis and a large multi-center magnetic resonance structural imaging (MRI) dataset, with a total of 1136 individuals, 415 with ASD (112 female; 303 male) and 721 controls (283 female; 438 male), we observed that individuals with ASD had significantly greater BSC in the bilateral superior temporal gyrus and left inferior frontal gyrus indicating an abrupt transition (high contrast) between white matter and cortical intensities. Increases were observed in different brain regions in males and females, with larger effect sizes in females. Individuals with ASD under 18 had significantly greater BSC in the bilateral superior temporal gyrus and right postcentral gyrus; individuals with ASD over 18 had significantly increased BSC in the bilateral precuneus and superior temporal gyrus. BSC correlated with ADOS-2 CSS in individuals with ASD in the right medial temporal pole. Importantly, there was a significant spatial overlap between maps of the effect of diagnosis on BSC when compared to cortical thickness. These results invite studies to use BSC as a possible new measure of cortical development in ASD and to further examine the microstructural underpinnings of BSC-related differences and their impact on measures of cortical morphology.

Autism is a heterogenous set of early-onset neurodevelopmental conditions that are more prevalent in males than in females. Due to the high phenotypic, neurobiological, developmental, and etiological heterogeneity in the autism spectrum, recent research programs are increasingly exploring whether sex- and gender-related factors could be helpful markers to clarify the heterogeneity in autism and work toward a personalized approach to intervention and support. In this chapter, we summarize recent clinical and neuroscientific research addressing sex/gender influences in autism and explore how sex/gender-based investigations shed light on similar or different underlying neurodevelopmental mechanisms of autism by sex/gender. We review evidence that may help to explain some of the underlying sex-related biological mechanisms associated with autism, including genetics and the effects of sex steroid hormones in the prenatal environment. We conclude that current research points toward coexisting quantitative and, perhaps more evidently, qualitative sex/gender-modulation effects in autism across multiple neurobiological aspects. However, converging findings of specific neurobiological presentations and sex/gender-informed mechanisms cutting across the many subgroups within the autism spectrum are still lacking. Future research should use big data approaches and new stratification methods to decompose sex/gender-related heterogeneity in autism and work toward personalized, sex/gender-informed intervention and support for autistic people.

Background Sociocommunicative difficulties, including abnormalities in eye contact, are core diagnostic features of autism spectrum disorder (ASD). Many studies have used eye tracking to measure reduced attention to faces in autistic people; however, most of this work has not taken advantage of eye-tracking temporal resolution to examine temporal profiles of attention. Methods We used growth curve analysis to model attention to static social scenes as a function of time in a large (N = 650) sample of autistic participants and neurotypical participants across a wide age range (6–30 years). Results The model yielded distinct temporal profiles of attention to faces in the groups. Initially, both groups showed a relatively high probability of attending to faces, followed by decline after several seconds. The neurotypical participants, however, were significantly more likely to return their attention to faces in the latter part of each 20-second trial, with increasing probability with age. In contrast, the probability of returning to the face in the autistic participants remained low across development. In participants with ASD, more atypical profiles of attention were associated with lower Vineland Adaptive Behavior Scales communication scores and a higher curvature in one data-driven cluster correlated with symptom severity. Conclusions These findings show that social attention not only is reduced in ASD, but also differs in its temporal dynamics. The neurotypical participants became more sophisticated in how they deployed their social attention across age, a pattern that was significantly reduced in the participants with ASD, possibly reflecting delayed acquisition of social expertise.

The male preponderance in autism prevalence has brought together the disparate topics of sex/gender and autism research. Two directions of neuroimaging studies on the relationships between sex/gender and autism may inform male-specific risk mechanisms and female-specific protective mechanisms of autism. First, we review how sex/gender moderates autism-related brain changes and how this informs general models of autism etiology. Better-powered human neuroimaging studies suggest that the brain characteristics of autism are qualitatively, rather than simply quantitatively, different between males and females. However, age and comorbidities might substantially moderate the pattern of differences. Second, we review how the relationship between autism-related brain changes (separately in males and females) and normative brain sex/gender differences informs specific etiological-developmental mechanisms. Both human and animal studies converge to indicate that the brain characteristics of autism are partly associated with normative brain sex/gender differences, suggesting convergence or overlap between the mechanisms leading to and modifying the development of autism and the mechanisms underlying sex differentiation and/or gender socialization. Future animal work needs to investigate sex differences in rodent mutants modeling autism-relevant genes and environmental exposures. Future human work needs to address the substantial phenotypic and etiological heterogeneity of autism and to focus on longitudinal neuroimaging studies (from early development) on the developmental trajectories of sex/gender-differential neural characteristics of autism. Combining animal and human work links up the causal chain from etiological factors, brain and physical development, to phenotypes. These together help delineate the different roles of sex and gender in relation to risk vs. protective mechanisms. © 2016 Wiley Periodicals, Inc.

Autism is a neurodevelopmental condition characterized by atypical brain functional organization. Here we investigated the intrinsic indirect (semi‐metric) connectivity of the functional connectome associated with autism. Resting‐state functional magnetic resonance imaging scans were acquired from 65 neurotypical adults (33 males/32 females) and 61 autistic adults (30 males/31 females). From functional connectivity networks, semi‐metric percentages (SMPs) were calculated to assess the proportion of indirect shortest functional pathways at global, hemisphere, network, and node levels. Group comparisons were then conducted to ascertain differences between autism and neurotypical control groups. Finally, the strength and length of edges were examined to explore the patterns of semi‐metric connections associated with autism. Compared with neurotypical controls, autistic adults displayed significantly higher SMP at all spatial scales, similar to prior observations in adolescents. Differences were primarily in weaker, longer‐distance edges in the majority between networks. However, no significant diagnosis‐by‐sex interaction effects were observed on global SMP. These findings suggest increased indirect functional connectivity in the autistic brain is persistent from adolescence to adulthood and is indicative of reduced functional network integration.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

Introduction In recent years, the universal right to education has been emphasised by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies relevant to special education needs and parental involvement of children with autism at an international level and in the Netherlands, Germany and Belgium. Methods A policy path analysis was performed using a scoping review as an underlying methodological framework. This allowed for a rapid gathering of available data from which a timeline of adopted policies was derived. Results and discussion Internationally, the universal right to education has been reinforced repeatedly and the values of the Universal Declaration of Human Rights have been reiterated with every reinforcement. Also, the additional support that a child with special education needs requires is acknowledged and measures are taken to facilitate access to any education for all children. There are slight cross-country differences between the countries under study, attributable to differences in national regulation of education. However, all countries have progressed to a state where the right to education for all children is integrated on a policy level and measures are taken to enable children with special needs to participate in education. Recently, an attempt to implement a form of inclusive education was made as a form of special needs provision. Nevertheless, nowhere has this been implemented successfully yet. Conclusion The Universal Declaration of Human Rights was a critical juncture in international policy and created an environment where the universal right to education has been implemented for all children in the countries under study.

Significant heterogeneity across aetiologies, neurobiology and clinical phenotypes have been observed in individuals with autism spectrum disorder (ASD). Neuroimaging-based neuroanatomical studies of ASD have often reported inconsistent findings which may, in part, be attributable to an insufficient understanding of the relationship between factors influencing clinical heterogeneity and their relationship to brain anatomy. To this end, we performed a large-scale examination of cortical morphometry in ASD, with a specific focus on the impact of three potential sources of heterogeneity: sex, age and full-scale intelligence (FIQ). To examine these potentially subtle relationships, we amassed a large multi-site dataset that was carefully quality controlled (yielding a final sample of 1327 from the initial dataset of 3145 magnetic resonance images; 491 individuals with ASD). Using a meta-analytic technique to account for inter-site differences, we identified greater cortical thickness in individuals with ASD relative to controls, in regions previously implicated in ASD, including the superior temporal gyrus and inferior frontal sulcus. Greater cortical thickness was observed in sex specific regions; further, cortical thickness differences were observed to be greater in younger individuals and in those with lower FIQ, and to be related to overall clinical severity. This work serves as an important step towards parsing factors that influence neuroanatomical heterogeneity in ASD and is a potential step towards establishing individual-specific biomarkers.

Many early-onset neurodevelopmental conditions such as autism affect males more frequently than females and affect corresponding domains such as social cognition, social-communication, language, emotion, and reward. Testosterone is well-known for its role as a sex-related biological mechanism and affects these conditions and domains of functioning. Developmentally, testosterone may sex-differentially impact early fetal brain development by influencing early neuronal development and synaptic mechanisms behind cortical circuit formation, particularly for circuits that later develop specialized roles in such cognitive domains. Here we find that variation in fetal testosterone (FT) exerts sex-specific effects on later adolescent functional connectivity between social brain default mode network (DMN) subsystems. Increased FT is associated with dampening of functional connectivity between DMN subsystems in adolescent males, but has no effect in females. To isolate specific prenatal neurobiological mechanisms behind this effect, we examined changes in gene expression identified following a treatment with a potent androgen, dihydrotestosterone (DHT) in an in-vitro model of human neural stem cell (hNSC). We previously showed that DHT-dysregulates genes enriched with known syndromic causes for autism and intellectual disability. DHT dysregulates genes in hNSCs involved in early neurodevelopmental processes such as neurogenesis, cell differentiation, regionalization, and pattern specification. A significant number of these DHT-dysregulated genes shows spatial expression patterns in the adult brain that highly correspond to the spatial layout of the cortical midline DMN subsystem. These DMN-related and DHT-affected genes (e.g., MEF2C) are involved in a number of synaptic processes, many of which impact excitation/inhibition imbalance. Focusing on MEF2C, we find replicable upregulation of expression after DHT treatment as well as dysregulated expression in induced pluripotent stem cells and neurons of individuals with autism. This work highlights sex-specific prenatal androgen influence on social brain DMN circuitry and autism-related mechanisms and suggests that such influence may impact early neurodevelopmental processes (e.g., neurogenesis, cell differentiation) and later developing synaptic processes.

Introduction: Autistic people may have different educational needs that need to be met to allow them to develop their full potential. Education and disability policies remain within the competence of EU Member States, with current educational standards and provisions for autistic people implemented locally. This scoping review aims to map EU and national special education policies with the goal of scoping the level of fulfilment of the right to education of autistic people. Methods: Four EU countries (United Kingdom, France, Poland and Spain) were included in this scoping review study. Governmental policies in the field of education, special education needs and disability law were included. Path dependency framework was used for data analysis; a net of inter-dependencies between international, EU and national policies was created. Results and discussion: Each country created policies where the right to free education without discrimination is provided. Poland does not have an autism specific strategy, whereas the United Kingdom, France and Spain have policies specifically designed for autistic individuals. Within the United Kingdom, all countries created different autism plans, nevertheless all aim to reach the same goal—inclusive education for autistic children that leads to the development of their full potential. Conclusion: Policy-making across Europe in the field of education has been changing through the years in favour of autistic people. Today their rights are noticed and considered, but there is still room for improvement. Results showed that approaches and policies vastly differ between countries, more Member States should be analysed in a similar manner to gain a broader and clearer view with a special focus on disability rights in Central and Eastern Europe. [ABSTRACT FROM AUTHOR]

Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0146-8) contains supplementary material, which is available to authorized users.

The male preponderance in autism prevalence has brought together the disparate topics of sex/gender and autism research. Two directions of neuroimaging studies on the relationships between sex/gender and autism may inform male-specific risk mechanisms and female-specific protective mechanisms of autism. First, we review how sex/gender moderates autism-related brain changes and how this informs general models of autism etiology. Better-powered human neuroimaging studies suggest that the brain characteristics of autism are qualitatively, rather than simply quantitatively, different between males and females. However, age and comorbidities might substantially moderate the pattern of differences. Second, we review how the relationship between autism-related brain changes (separately in males and females) and normative brain sex/gender differences informs specific etiological-developmental mechanisms. Both human and animal studies converge to indicate that the brain characteristics of autism are partly associated with normative brain sex/gender differences, suggesting convergence or overlap between the mechanisms leading to and modifying the development of autism and the mechanisms underlying sex differentiation and/or gender socialization. Future animal work needs to investigate sex differences in rodent mutants modeling autism-relevant genes and environmental exposures. Future human work needs to address the substantial phenotypic and etiological heterogeneity of autism and to focus on longitudinal neuroimaging studies (from early development) on the developmental trajectories of sex/gender-differential neural characteristics of autism. Combining animal and human work links up the causal chain from etiological factors, brain and physical development, to phenotypes. These together help delineate the different roles of sex and gender in relation to risk vs. protective mechanisms. © 2016 Wiley Periodicals, Inc.

Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n = 694; n = 249), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 45–62% of ASC adults show evidence for large impairments (Cohen’s d = −1.03 to −11.21), while other subgroups are effectively unimpaired. These findings delineate robust natural subdivisions within the ASC population that may allow for more individualized inferences and accelerate research towards precision medicine goals.

Individuals affected by autism spectrum conditions (ASC) are considerably heterogeneous. Novel approaches are needed to parse this heterogeneity to enhance precision in clinical and translational research. Applying a clustering approach taken from genomics and systems biology on two large independent cognitive datasets of adults with and without ASC (n=715; n=251), we find replicable evidence for 5 discrete ASC subgroups that are highly differentiated in item-level performance on an explicit mentalizing task tapping ability to read complex emotion and mental states from the eye region of the face (Reading the Mind in the Eyes Test; RMET). Three subgroups comprising 42-65% of ASC adults show evidence for large impairments (Cohen’s d = −1.03 to −11.21), while other subgroups are effectively unimpaired. These findings delineate robust natural subdivisions within the ASC population that may allow for more individualized inferences and accelerate research towards precision medicine goals.

Background Autism is a highly heritable condition, and common variants explain approximately 50% of the genetic variance of autism. Individuals with autism typically have difficulties with social interactions, which may be due to altered social cognition. Variants in the Oxytocin Receptor (OXTR) have been implicated in both autism and social cognition. Functional neuroimaging studies on the brain’s response to social tasks in individuals with autism have yielded mixed findings. This may not be surprising as autism is a heterogeneous neurodevelopmental condition, with varied genetic and biological aetiologies. In the current study we combine genetics and functional neuroimaging to investigate the biological basis of differences in social cognition in autism. Methods Participants were adolescents (12-18 years old): 41 (11 females) were diagnosed with high-functioning autism or Asperger syndrome (autism group) and 33 (17 females) were typically developing (control group). Participants provided buccal DNA samples and these were genotyped for 7 Single Nucleotide Polymorphisms (SNPs) in the OXTR; of these, 2 had little variance in the sample and were excluded from further analysis. The remaining 5 SNPs were rs2254298, rs53576, rs2268491, rs2228485, and rs7632287. The participants were scanned using a Siemens 3-T TimTrio scanner (Siemens Healthcare, Germany) while completing the adolescent version of the ‘Reading the Mind in the Eyes’ Test. We conducted a whole brain analysis (controlling for sex and age) and examined the effect of genotype, diagnosis and the interaction between genotype and diagnosis on brain activation during the Eyes test. Analyses were conducted for each SNP separately. Results Examining brain activation when making a mental state decision, versus deciding the sex of the portrayed character (baseline condition), we found 3 SNPs with significant effects. For rs2254298 and rs53576 a region overlapping with the Inferior Parietal Lobule (IPL) showed hyperactivation during the mental state condition depending on genotype (F(1,60)=11.97, p value(FWE-corr)=0.010 and F(1,60)=11.97, p value(FWE-corr)=0.006, respectively) and on the interaction between genotype and diagnosis (F(1,60)=11.97, p value (FWE-corr)=0.009 and F(1,60)=11.97, p value (FWE-corr)=0.034, respectively). Increased activation in a region overlapping with the IPL was also found for rs2268491, but this was associated with the interaction only (F(1,60)=11.93, p value (FWE-corr)=0.009). For 2 (rs2228485, rs7632287) of the 5 SNPs, no cluster survived the family-wise correction (FWE) set at 0.05. Discussion The current study provides preliminary evidence that brain activation in response to a social task may be associated with both diagnostic status and common variation in the OXTR. Importantly, the IPL has been previously implicated in the affect sharing system. An imaging genetics approach might lend itself to increasingly accurate understanding of the heterogeneous autism phenotype.

Item does not contain fulltext INTRODUCTION: Reducing fear when a threat has disappeared protects against a continuously elevated anxiety state. In this study, we investigated the brain mechanism involved in this process. METHODS: The threat paradigm consisted of discrete cues that signaled either threat of shock or safety. Healthy participants were tested in two sessions in which eyeblink startle (n = 26) and blood oxygen level dependence (n = 23) were measured to index subjects' defensive state and brain responses respectively. RESULTS: Startle results indicated that subjects could rapidly decrease their defensive state after the offset of shock threat. Functional magnetic resonance imaging data indicated that the termination of threat was associated with the recruitment of lateral and ventromedial prefrontal cortices. An exploratory connectivity analysis showed that activity in these prefrontal regions was linked and was also associated with activity in brain regions typically responding to threat, the right anterior insula and amygdala. CONCLUSIONS: These results provide first evidence for a prefrontal mechanism that functions to control anxiety after threat offset, which may be dysfunctional in patients who suffer from excessive sustained anxiety. Moreover, the results support a model in which the lateral prefrontal cortex controls anxiety related limbic activity through connections with ventromedial prefrontal cortex.

Functional magnetic resonance imaging (fMRI) research is routinely criticized for being statistically underpowered due to characteristically small sample sizes and much larger sample sizes are being increasingly recommended. Additionally, various sources of artifact inherent in fMRI data can have detrimental impact on effect size estimates and statistical power. Here we show how specific removal of non-BOLD artifacts can improve effect size estimation and statistical power in task-fMRI contexts, with particular application to the social-cognitive domain of mentalizing/theory of mind. Non-BOLD variability identification and removal is achieved in a biophysical and statistically principled manner by combining multi-echo fMRI acquisition and independent components analysis (ME-ICA). Without smoothing, group-level effect size estimates on two different mentalizing tasks were enhanced by ME-ICA at a median rate of 24% in regions canonically associated with mentalizing, while much more substantial boosts (40- 149%) were observed in non-canonical cerebellar areas. Effect size boosting occurs via reduction of non-BOLD noise at the subject-level and consequent reductions in betweensubject variance at the group-level. Smoothing can attenuate ME-ICA-related effect size improvements in certain circumstances. Power simulations demonstrate that ME-ICArelated effect size enhancements enable much higher-powered studies at traditional sample sizes. Cerebellar effects observed after applying ME-ICA may be unobservable with conventional imaging at traditional sample sizes. Thus, ME-ICA allows for principled design-agnostic non-BOLD artifact removal that can substantially improve effect size estimates and statistical power in task-fMRI contexts. ME-ICA could mitigate some issues regarding statistical power in fMRI studies and enable novel discovery of aspects of brain organization that are currently under-appreciated and not well understood., This work was supported by a Wellcome Trust project grant to SB-C and ETB. MVL was supported by the Wellcome Trust and fellowships from Jesus College, Cambridge and the British Academy. PK was supported by the National Institutes of Health–Cambridge Scholars Program. ETB is employed half-time by the University of Cambridge and halftime by GlaxoSmithKline (GSK)., This is the author accepted manuscript. It first appeared from Elseiver at http://dx.doi.org/10.1016/j.neuroimage.2016.07.022.

Introduction The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and discussion The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems while emphasising the need to include as many children in the mainstream system as possible.

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry., Natasha Bertelsen et al. develop a computational model to categorize patients with autism spectrum disorder (ASD) into distinct subgroups, based on social-communicative or restricted repetitive behaviors. By integrating publicly available neuroimaging and genetic data, they report neural and molecular signatures in two of these subgroups, altogether highlighting subtle differences in neural circuitry and genomic networks that could underlie phenotypic differences among ASD patients.