Search

Approximately 40% of American adults are affected by cardiovascular disease (CVD) risk factors (e.g., high blood pressure, high cholesterol, diabetes, and overweight or obesity), and risk among autistic adults may be even higher. Mechanisms underlying the high prevalence of CVD risk factors in autistic people may include known correlates of CVD risk factors in other groups, including high levels of perceived stress, poor sleep quality, and antipsychotic medication use. A sample of 545 autistic adults without intellectual disability aged 18+ were recruited through the Simons Foundation Powering Autism Research, Research Match. Multiple linear regression models examined the association between key independent variables (self-reported perceived stress, sleep quality, and antipsychotic medication use) and CVD risk factors, controlling for demographic variables (age, sex assigned at birth, race, low-income status, autistic traits). Overall, 73.2% of autistic adults in our sample had an overweight/obesity classification, 45.3% had high cholesterol, 39.4% had high blood pressure, and 10.3% had diabetes. Older age, male sex assigned at birth, and poorer sleep quality were associated with a higher number of CVD risk factors. Using antipsychotic medications was associated with an increased likelihood of having diabetes. Poorer sleep quality was associated with an increased likelihood of having an overweight/obesity classification. Self-reported CVD risk factors are highly prevalent among autistic adults. Both improving sleep quality and closely monitoring CVD risk factors among autistic adults who use antipsychotic medications have the potential to reduce risk for CVD.

Objective: Later autism diagnosis is associated with increased mental health risks. Thus, understanding factors related to disparities in diagnostic timing is important to reduce psychiatric burden for autistic people at disproportionate risk for mental health problems. “Sex” has captured attention in relation to differences in timing in autism recognition and diagnosis. However, literature to date does not characterize, differentiate, or account for gender identity beyond assigned sex at birth. Consideration of gender is key, as gender diversity may be more common in autistic relative to neurotypical people, and autism is proportionally overrepresented in gender-diverse populations. We examined age at autism diagnosis by assigned sex at birth, gender identity, and gender diversity (gender-diverse vs. cisgender) status, separately.Method: Three independent autistic cohorts representing different ascertainments were examined: a research-recruited academic medical center sample (N=193; aged 8.0-18.0y); a clinic-based sample (N=1550; 1.3-25.4y); and a community-enriched sample (N=244, 18.2-30.0y).Results: Disparities in diagnostic timing were observed in the clinic-based and community-enriched samples: people assigned female at birth, people of female gender, and gender-diverse people were diagnosed with autism significantly later than persons assigned male at birth, persons of male gender, and cisgender persons, respectively.Conclusion: Sex at birth, gender identity, and gender diversity may each uniquely relate to disparities in diagnostic timing of autism. The influence of ascertainment strategies, particularly in studies examining assigned sex at birth or gender identity, should be considered. Further research into autism diagnosis in adulthood and the role of sociodemographic factors is needed.

Purpose: Although autistic adults have demonstrated weaker memory performance on lab-based measures in comparison to neurotypical peers, research on self-reported memory abilities in this group is scarce. Shedding light on memory abilities of autistic adults is important, as memory difficulties may impact daily living outcomes, an area of known weakness for autistic individuals. Thus, the current study aimed to characterize the self-reported memory complaints of large sample of autistic adults in comparison to neurotypical adults.Methods: The responses to the Prospective and Retrospective Memory Questionnaire were compared by diagnostic group and within the autistic group, relations between memory complaints and real-world outcomes (activities of daily living [ADLs] and postsecondary employment and educational activities) were examined.Results: The results indicated that autistic adults reported greater memory problems than neurotypical peers, regardless of memory type, and autistic adults reported a comparable pattern of complaints as their neurotypical peers (i.e., greater prospective memory complaints in comparison to retrospective memory complaints). Additionally, we found a negative association between memory complaints and outcomes (i.e., greater memory complaints were associated with less independence in ADLs and poorer postsecondary outcomes). Conclusions: The significant association between subjective memory complaints and real-world outcomes suggests targeting memory abilities may result in downstream improvements in daily living skills and post-secondary outcomes among autistic adults.

Background Sex chromosome aneuploidies (SCAs) are a collectively common family of genetic disorders that increase the risk for neuropsychiatric and cognitive impairment. Beyond being important medical disorders in their own right, SCAs also offer a unique naturally occurring model for studying X- and Y-chromosome influences on the human brain. However, it remains unclear if (i) different SCAs are associated with different profiles of psychopathology and (ii) the notable interindividual variation in psychopathology is related to co-occurring variation in cognitive ability. Methods We examined scores for 11 dimensions of psychopathology [Child/Adult Behavior Checklist (CBCL)] and general cognitive ability [full-scale IQ (FSIQ) from Wechsler tests] in 110 youth with varying SCAs (XXY = 41, XYY = 22, XXX = 27, XXYY = 20) and 131 typically developing controls (XX = 59, XY = 72). Results All SCAs were associated with elevated CBCL scores across several dimensions of psychopathology (two-sample t tests comparing the euploidic and aneuploidic groups [all |T| > 9, and p < 0.001]). Social and attentional functioning were particularly sensitive to the carriage of a supernumerary Y-chromosome. In particular, the XYY group evidenced significantly more social problems than both extra-X groups (Cohen’s d effect size > 0.5, Bonferroni corrected p < .05). There was marked variability in CBCL scores within each SCA group, which generally correlated negatively with IQ, but most strongly so for social and attentional difficulties (standardized β, − 0.3). These correlations showed subtle differences as a function of the SCA group and CBCL scale. Conclusions There is domain-specific variation in psychopathology across SCA groups and domain-specific correlation between psychopathology and IQ within SCAs. These findings (i) help to tailor clinical assessment of this common and impactful family of genetic disorders and (ii) suggest that dosage abnormalities of X- and Y-linked genes impart somewhat distinct profiles of neuropsychiatric risk.

Objective: Self-reported memory difficulties are common among older adults, but few studies have examined memory problems among autistic middle-aged and older people. The current study examines self-rated prospective (PM) and retrospective (RM) memory difficulties and their associations with age in middle-aged and older autistic and non-autistic people.Methods: 350 autistic people (58% assigned-female-at-birth; age-range: 40-83 years) and 350 non-autistic adults matched on age, birth-sex and education level were included in the analysis. Participants completed the Prospective and Retrospective Memory Questionnaire (PRMQ) which includes questions about PM vs. RM (memory type), environment-cued vs. self-cued (cue), and short vs. long delay (delay). Results: Autistic people reported significantly more PM and RM difficulties than the comparison group. Both groups reported more difficulties with PM (vs. RM), self-cued (vs. environment-cued), and short (vs. long) delay. No significant interactions were observed. Among autistic people, younger age was associated with reporting more PM and RM difficulties, but this pattern was not observed among non-autistic people. Conclusions: Autistic people may be at reduced risk for memory problems as they age, compared to their same-age non-autistic peers. Further studies are required to explore the association between self-reported memory challenges and memory task performance among autistic older people.

Camouflaging is associated with anxiety and depression in autistic adults; however, what drives these associations is unclear. We examined two potential drivers of the association between camouflaging and anxiety/depression: perceived stress and emotion regulation. 787 autistic adults (18.2-78.2 years) recruited via Simons Powering Autism Research (SPARK) Research Match completed questionnaires, including the Camouflaging Autistic Traits Questionnaire (CAT-Q), and measures of autistic traits, depressive and anxious symptomatology, perceived stress, and emotion regulation. Four moderated mediation models were tested. In all models the independent variable was CAT-Q total score, and the moderator variable was birth-sex. The dependent variable was depressive or anxious symptomatology, and the mediator variable was perceived stress or emotion regulation. In what is, to our knowledge, the first study to examine potential drivers of associations between camouflaging and depression/anxiety, we found that perceived stress and emotion regulation each significantly mediated the associations between camouflaging and both depression and anxiety. In the model with perceived stress and anxiety, sex moderated the mediation, with females showing a stronger mediation. There was no significant moderation in any of the other models. We contextualize the findings within the broader literature on camouflaging as a response to stigma and other facets of minority stress.

Camouflaging in autism spectrum disorder could be a factor in later diagnosis of individuals without co-occurring intellectual disability, particularly among those designated female sex at birth. Little research to date has examined how gender identity impacts camouflaging, however. Further, no study has compared groups that differ in diagnostic timing to directly investigate if later-diagnosed individuals demonstrate elevated camouflaging relative to those receiving an earlier diagnosis. Using the Camouflaging Autistic Traits Questionnaire subscales (Assimilation, Compensation, and Masking), we investigated the roles of sex, gender identity (gender diverse vs cisgender), and diagnostic timing (childhood/adolescent-diagnosed vs adult-diagnosed), and the interactions of these factors, in autistic adults ( N = 502; age 18–49 years). Main effects of sex, gender identity, and diagnostic timing were revealed. Autistic females reported more camouflaging across Camouflaging Autistic Traits Questionnaire subscales compared to males. Gender diverse adults reported elevated camouflaging on the Compensation subscale compared to cisgender adults. Adulthood-diagnosed individuals reported elevated Assimilation and Compensation compared to childhood/adolescence-diagnosed individuals. We discuss how aspects of camouflaging may have particular implications for later diagnostic timing and for the intersection of neurodiversity and gender diversity. Lay abstract Camouflaging in autism spectrum disorder refers to behaviors and/or strategies that mask the presentation of autism spectrum disorder features in social contexts in order to appear “non-autistic” (Attwood, 2007). Camouflaging modifies the behavioral presentation of core autism spectrum disorder features (e.g. social and communication differences), but the underlying autistic profile is unaffected, yielding a mismatch between external observable features and the internal lived experience of autism. Camouflaging could be an important factor in later diagnosis of individuals without co-occurring intellectual disability, especially among those designated female sex at birth. Little research to date has examined how gender identity impacts camouflaging, however. Furthermore, no study has compared groups that differ in diagnostic timing to directly investigate if later-diagnosed individuals show elevated camouflaging relative to those receiving an earlier diagnosis. We used the Camouflaging Autistic Traits Questionnaire subscales (Assimilation, Compensation, and Masking) and investigated the roles of sex, gender identity (gender diverse vs cisgender), and diagnostic timing (childhood/adolescent-diagnosed vs adult-diagnosed), and the interactions of these factors, in autistic adults ( N = 502; ages 18–49 years). Main effects of sex, gender identity, and diagnostic timing were revealed. Autistic females reported more camouflaging across all three Camouflaging Autistic Traits Questionnaire subscales compared to males. Gender diverse adults reported elevated camouflaging on the Compensation subscale compared to cisgender adults. Adulthood-diagnosed individuals reported elevated Assimilation and Compensation compared to childhood/adolescence-diagnosed individuals. We discuss how the aspects of camouflaging may have unique implications for later diagnostic timing and for the intersection of neurodiversity and gender diversity.

Outcomes for autistic adults are generally poor across multiple foundational metrics, including activities of daily living and quality of life. Co-occurring psychiatric conditions contribute to these poor outcomes. Attention-deficit/hyperactivity disorder is one of the most common co-occurring conditions among autistic individuals; however, we know little about the association of attention-deficit/hyperactivity disorder symptoms with autistic adult outcomes. A total of 724 autistic adults (18–83 years; 58% female) recruited via Simons Foundation Powering Autism Research (SPARK) Research Match completed questionnaires on demographics, co-occurring attention-deficit/hyperactivity disorder symptoms, activities of daily living, and subjective quality of life. After controlling for age, birth-sex, socioeconomic status, and autistic traits, attention-deficit/hyperactivity disorder symptoms explained an additional 2%−10% of variance across activities of daily living and all domains of subjective quality of life. This is the first study to demonstrate that autistic adults who rated themselves as having more attention-deficit/hyperactivity disorder symptoms also rated themselves as less independent in activities of daily living and experiencing a lower subjective quality of life. These findings highlight that additional research and better supports for co-occurring attention-deficit/hyperactivity disorder symptoms may be critical to enhancing independence and quality of life for autistic adults.Lay abstractOutcomes for autistic adults are generally poor, including activities of daily living and self-ratings of quality of life. Co-occurring psychiatric conditions contribute to these poor outcomes. Attention-deficit/hyperactivity disorder is one of the most common co-occurring conditions in autistic individuals. However, we know little about the association between attention-deficit/hyperactivity disorder symptoms and outcomes in autistic adults. A total of 724 autistic adults (18–83 years; 58% female) recruited from the Simons Foundation Powering Autism Research participant registry completed questionnaires on demographics, co-occurring psychiatric conditions, activities of daily living, and subjective quality of life. Autistic adults who rated themselves as having more attention-deficit/hyperactivity disorder symptoms also rated themselves as having less independence in activities of daily living and a lower quality of life. This is the first study to show these relationships in autistic adults. These findings highlight that additional research and better supports for co-occurring attention-deficit/hyperactivity disorder symptoms may be critical to improving independence and quality of life for autistic adults.

Background Down syndrome (DS) is a disorder characterized by impairments in global cognitive abilities and adaptive function. In addition, individuals with DS demonstrate pronounced speech and language deficits. However, little is known about the linguistic correlates of impaired adaptive functioning in DS. Method Using the Adaptive Behavior Assessment System–Second Edition and the Children's Communication Checklist–Second Edition (CCC-2), this study investigated the unique variance in adaptive skills accounted for by speech and language impairments in individuals with DS ( N = 29, M age = 13.46). Results Pearson correlations revealed that a composite of CCC-2 structural language scales, but not pragmatic language scales, was significantly correlated with the Adaptive Behavior Assessment System–Second Edition Global Adaptive Composite, Conceptual, and Practical domains. Further investigation utilizing hierarchical regression analyses identified only the Speech scale on the CCC-2 as contributing unique variance to the prediction of adaptive behavior scores in the Global Adaptive Composite, Conceptual, and Practical domains. Conclusion Speech impairments may serve as flags to identify children with DS who are at risk for adaptive behavior deficits and reinforce the need for speech-language therapies that focus on speech for these individuals. Supplemental Material https://doi.org/10.23641/asha.13231985

Little is known about work readiness skills among autistic adults. This study sought to address this by examining work readiness skills and their relation to vocational outcomes among 281 autistic young adults. It also examined perceived barriers and facilitators to employment as articulated by 41 autistic adults. Results revealed a variegated work readiness profile. Stronger work readiness skills (particularly work style/adaptability) were associated with more favorable vocational outcomes. Autistic participants articulated both barriers and facilitators to employment related to the autism phenotype, job search/work readiness, and workplace education. These findings highlight the need for research on phenotype-driven vocational rehabilitation strategies as well as workplace psychoeducation/accommodations to support vocational outcomes for autistic adults.

Poor sleep can have a significant impact on physical health and well-being. Sleep problems are common among autistic children, but little is known about sleep across the autistic adult lifespan. Autistic adults (n=730, aged 18-78 years) were recruited via Simons Powering Autism Research for Knowledge (SPARK) Research Match. Participants completed online surveys asking about demographics, health problems, social support, symptoms of anxiety and depression, and overall and specific aspects of sleep quality. Regression analyses explored the variables associated with sleep quality. Physical health, female sex and self-reported anxiety symptoms significantly contributed to models for all aspects of sleep. Perceived stress contributed to models of overall and subjective sleep quality, sleep disturbance and daytime dysfunction. Depression symptoms contributed to models of subjective sleep quality and sleep duration; whereas utilising government support mechanisms (such as social security) contributed to the model of sleep efficiency. Age did not contribute significantly to models after accounting for perceived stress, depressive and anxiety symptoms. Sleep quality is poor for autistic people across the adult lifespan. Given known impacts of poor sleep on health, cognition and quality of life, attention should be paid to sleep and its possible effects for autistic people of all ages.

Down syndrome (DS) is associated with significant memory deficits beyond overall global cognitive impairment. Although a number of studies have examined memory abilities in adults and teens with DS, very few studies have examined memory abilities in children with DS. Additionally, research has yet to examine prospective memory (i.e., remembering to carry out an action in the future) in youth with DS. Consequently, the current study aimed to comprehensively examine the memory profile, including learning, immediate recall, delayed recall and prospective memory, of youth with DS (n = 22, age M = 11.43) in comparison to typically developing, mental-age (MA) matched children (n = 20, age M = 5.04) Consistent with past research, the results indicated that youth with DS performed significantly below MA-expectations on tasks of immediate verbal recall, learning across trials, and prospective memory, and there was a trend toward youth with DS performing below MA-expectations on delayed recall tasks. However, youth with DS did not differ significantly from MA-matched peers on immediate visual recall, rate of learning across trials, or proportion of items recalled on verbal and visual memory tasks following a delay (i.e., proportion relative to their own recall performance prior to the delay). These results highlight the relative strengths and challenges experienced by youth with DS on different learning and memory tasks. The implications of these findings for educators and caregivers are discussed.

Few studies have examined self-reported perceived stress in autistic adults. Existing studies have included relatively small, predominantly male samples and have not included older autistic adults. Using a large autistic sample (N = 713), enriched for individuals designated female at birth (59.3%), and spanning younger, middle, and older adulthood, we examined perceived stress and its associations with independence in activities of daily living and subjective quality of life (QoL). Perceived stress for autistic adults designated male or female at birth was compared to their same birth-sex counterparts in a general population sample. In addition, within the autistic sample, effects of sex designated at birth, age, and their interaction were examined. Regression modeling examined associations between perceived stress and independence in activities of daily living and domains of subjective QoL in autistic adults, after controlling for age, sex designated at birth, and household income. Autistic adults reported significantly greater perceived stress than a general population comparison sample. Relative to autistic adults designated male at birth, those designated female at birth demonstrated significantly elevated perceived stress. Perceived stress contributed significantly to all regression models, with greater perceived stress associated with less independence in activities of daily living, and poorer subjective QoL across all domains-Physical, Psychological, Social, Environment, and Autism-related QoL. Findings are contextualized within the literature documenting that autistic individuals experience elevated underemployment and unemployment, heightened rates of adverse life events, and increased exposure to minority stress. LAY SUMMARY: This study looked at self-reported perceived stress in a large sample of autistic adults. Autistic adults reported more perceived stress than non-autistic adults. Autistic individuals designated female at birth reported higher stress than autistic individuals designated male at birth. In autistic adults, greater perceived stress is related to less independence in activities of daily living and poorer subjective quality of life.

Background: Although disparities in mental health and subjective quality of life have been reported for autistic adults, reasons for these disparities are poorly understood. A potential factor in these disparities is exposure to social stressors related to minority status (i.e., minority stress), including stigma and discrimination. Autistic individuals are more likely than non-autistic individuals to possess other minority identities, including sexual minority identities. However, to date, few studies have examined whether sexual minority autistic adults experience diminished mental health relative to heterosexual autistic adults, and no research has examined subjective quality of life for sexual minority compared to heterosexual autistic adults.Methods: Participants were 679 autistic adults aged 18.5 to 83.3 years recruited through Simons Powering Autism Research Knowledge Research Match. Participants completed surveys online, including measures of anxious and depressive symptomatology, perceived stress, and subjective quality of life. Participants reported their sexual orientation and other socio-demographic variables. Results: A large proportion of autistic adults reported a sexual minority identity (43.4%). Sexual minority autistic adults showed poorer mental health and lower subjective quality of life relative to heterosexual autistic adults. Diminished quality of life in the sexual minority group appears to be driven by the strength of the effects for gay and pansexual compared to heterosexual autistic adults. Conclusion: Understanding factors that may be related to poorer mental health and decreased subjective quality of life in autistic adults is critical and has been identified as a research priority among autistic stakeholders. The findings reported here underscore the need to examine mental health and subjective quality of life disparities among autistic individuals within a societal context, taking into consideration the potential of intersecting minority identities and increased social stressors, as these hold the potential to increase risks for poorer outcome.

Studies of resting-state functional connectivity in young people with Down syndrome (DS) have yielded conflicting results. Some studies have found increased connectivity while others have found a mix of increased and decreased connectivity. No studies have examined whole-brain connectivity at the voxel level in youth with DS during an eyes-open resting-state design. Additionally, no studies have examined the relationship between connectivity and network selectivity in youth with DS. Thus, the current study sought to fill this gap in the literature. Nineteen youth with DS (M

Across all ages, individuals with Down syndrome (DS) experience high rates of sleep problems as well as cognitive impairments. This study sought to investigate whether circadian rhythm disruption was also experienced by people with DS and whether this kind of sleep disorder may be correlated with cognitive performance. A cross-sectional study of 101 participants (58 with DS, 43 with typical development) included individuals in middle childhood (6–10 years old), adolescence (11–18 years old), and young adulthood (19–26 years old). Sleep and markers of circadian timing and robustness were calculated using actigraphy. Cognitive and behavioral data were gathered via a novel touchscreen battery (A-MAPTM, Arizona Memory Assessment for Preschoolers and Special Populations) and parent questionnaire. Results indicated that children and adolescents with DS slept the same amount as peers with typical development, but significant group differences were seen in phase timing. The circadian robustness markers, interdaily stability and intradaily variability of sleep-wake rhythms, were healthiest for children regardless of diagnostic group and worst for adults with DS. Amplitude of the 24-h activity profile was elevated for all individuals with DS. In analyses of the correlations between sleep quality, rhythms, and cognition in people with DS, interdaily stability was positively correlated with reaction time and negatively correlated with verbal and scene recall, a finding that indicates increased stability may paradoxically correlate with poorer cognitive outcomes. Further, we found no relations with sleep efficiency previously found in preschool and adult samples. Therefore, the current findings suggest that a thorough examination of sleep disorders in DS must take into account age as well as circadian robustness to better understand sleep-cognitive correlations in this group.

Gene dosage disorders (GDDs) constitute a major class of genetic risks for psychopathology, but there is considerable debate regarding the extent to which different GDDs induce different psychopathology profiles. The current research speaks to this debate by compiling and analyzing dimensional measures of several autism-related traits (ARTs) across seven diverse GDDs. The sample included 350 individuals with one of 7 GDDs, as well as reference idiopathic autism spectrum disorder (ASD; n = 74) and typically developing control (TD; n = 171) groups. The GDDs were: Down, Williams-Beuren, and Smith-Magenis (DS, WS, SMS) syndromes, and varying sex chromosome aneuploidies ("plusX", "plusXX", "plusY", "plusXY"). The Social Responsiveness Scale (SRS-2) was used to measure ARTs at different levels of granularity-item, subscale, and total. General linear models were used to examine ART profiles in GDDs, and machine learning was used to predict genotype from SRS-2 subscales and items. These analyses were completed with and without covariation for cognitive impairment. Twelve of all possible 21 pairwise GDD group contrasts showed significantly different ART profiles (7/21 when co-varying for IQ, all Bonferroni-corrected). Prominent GDD-ART associations in post hoc analyses included relatively preserved social motivation in WS and relatively low levels of repetitive behaviors in plusX. Machine learning revealed that GDD group could be predicted with plausible accuracy (~60-80%) even after controlling for IQ. GDD effects on ARTs are influenced by GDD subtype and ART dimension. This observation has consequences for mechanistic, clinical, and translational aspects of psychiatric neurogenetics.

Outcomes for autistic adults are generally poor across multiple foundational metrics, including quality of life and activities of daily living. Co occurring psychiatric conditions, including depression and anxiety, contribute to these poor outcomes. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common co-occurring conditions in autistic individuals, yet its association with adult outcomes is largely unknown. 628 autistic adults (18-83 years; 58% female) recruited from the Simons Foundation Powering Autism Research for Knowledge cohort completed questionnaires on demographics, co occurring mental health conditions, activities of daily living and subjective quality of life. After controlling for age, birth-sex, socioeconomic status, autistic traits, and ADHD medications, ADHD symptoms explained an additional 2 to 9% of variance across activities of daily living and all domains of subjective quality of life. This is the first study to demonstrate an association between self-reported ADHD symptoms and lower activities of daily living and subjective quality of life ratings by autistic adults. These findings highlight that additional research and better supports for co-occurring ADHD symptoms may be critical to enhancing independence and quality of life for autistic adults.

Background Down syndrome (DS) is associated with increased rates of autism spectrum disorder (ASD), characterized by social−communicative impairments (SOC−COM) and repetitive behaviors and interests (RBI). However, little is known about the ASD symptom presentation in children with DS + ASD. Aims The current study sought to describe parent-report of SOC−COM and RBI symptoms on the Autism Diagnostic Interview -Revised (ADI-R) in children with DS (n = 22), DS + ASD (n = 11), and ASD (n = 66). Method SOC−COM and RBI scores from the ADI-R were compared across the groups whose autism status was ascertained using the Autism Diagnostic Observation Schedule. Results Differences in SOC−COM and RBI symptom severity was observed. The general pattern of findings was ASD > DS+ASD > DS. Dissimilar ASD symptom profiles were observed across groups. In ASD, SOC−COM scores were higher than RBI scores; in DS + ASD, similar SOC−COM and RBI scores were observed. Lastly, SOC−COM impairments were highly related to verbal cognition in youth with DS + ASD but not in those with DS or ASD. Conclusions and Implications These findings suggest that children with DS + ASD have a distinct profile of ASD symptoms that differs from peers with either disorder in isolation. Thus, care should be taken in evaluating and designing treatments for this group.

Camouflaging in autism spectrum disorder (ASD) could be a factor in later diagnosis of individuals without co-occurring intellectual disability, particularly among those assigned female sex at birth. Little research to date has examined how gender identity impacts camouflaging, however. Further, no study has compared groups that differ in diagnostic-timing to directly investigate if later-diagnosed individuals demonstrate elevated camouflaging relative to those receiving an earlier diagnosis. Using the Camouflaging Autistic Traits Questionnaire (CAT-Q) subscales (Assimilation, Compensation, and Masking), we investigated the roles of sex, gender identity (gender diverse vs. cisgender), and diagnostic timing (childhood/adolescent-diagnosed vs. adult-diagnosed), and the interactions of these factors, in ASD adults (N=502; ages 18-49 years). Main effects of sex, gender identity, and diagnostic-timing were revealed. ASD females reported more camouflaging across CAT-Q subscales compared to males. Gender diverse adults reported elevated camouflaging on the Compensation subscale compared to cisgender adults. Adulthood-diagnosed individuals reported elevated Assimilation and Compensation compared to childhood/adolescence-diagnosed individuals. We discuss how the ‘performative’ aspects of camouflaging probed in the Assimilation and Compensation subscales may have particular implications for the intersection of neurodiversity and gender diversity, and for later diagnostic timing.

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.

Research on the developing brain in persons with Down syndrome has grown in recent years thanks to advances in neuroimaging approaches that are safe for pediatric populations. This literature documents global reductions in total brain volume as well as specific alterations in both cortical and subcortical structures. These include reductions in hippocampal and cerebellar volumes (that are in excess of reduced total brain volume) as well as abnormalities in frontal and temporal lobe anatomy. Recent neuroimaging research has highlighted the importance of using fine-grained approaches to characterizing cortical and subcortical anatomy in persons with Down syndrome as well as interpreting these findings within the context of research on typical brain development. In the current review, we attempt to synthesize this literature from a developmental perspective. Our hope is that this developmental focus will lead to discoveries about the biological underpinnings and unfolding of the learning difficulties associated with Down syndrome.

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data., How neurodevelopmental disorder-associated risk genes are translated into spatially patterned brain vulnerabilities is unclear. Here, the authors show that disorder-specific patterns of neuroanatomical changes are aligned to brain expression maps of disease risk genes in healthy subjects.

Quantitative magnetic resonance imaging (MRI) investigations of brain anatomy in children and young adults with Down syndrome (DS) are limited, with no diffusion tensor imaging (DTI) studies covering that age range. We used DTI-driven tensor based morphometry (DTBM), a novel technique that extracts morphometric information from diffusion data, to investigate brain anatomy in 15 participants with DS and 15 age- and sex-matched typically developing (TD) controls, ages 6–24 years (mean age ~17 years). DTBM revealed marked hypoplasia of cerebellar afferent systems in DS, including fronto-pontine (middle cerebellar peduncle) and olivo-cerebellar (inferior cerebellar peduncle) connections. Prominent gray matter hypoplasia was observed in medial frontal regions, the inferior olives, and the cerebellum. Very few abnormalities were detected by classical diffusion MRI metrics, such as fractional anisotropy and mean diffusivity. Our results highlight the potential importance of cerebro-cerebellar networks in the clinical manifestations of DS and suggest a role for DTBM in the investigation of other brain disorders involving white matter hypoplasia or atrophy.

Language and executive functioning are major impairments in many neurodevelopmental disorders, but little is known about the relations between these constructs, particularly using parent-report. Thus, the current research sought to examine relations between executive function and language in two groups -- Down syndrome (DS) and autism spectrum disorder (ASD). Forty-one youth with DS (M(age)=11.2) and 91 youth with ASD (M(age)= 7.7) were included. Results were as follows: in DS, executive function predicted pragmatic, but not structural language, after covarying for age, sex, and social functioning; in ASD, executive function predicted both. Findings highlight the interrelatedness of language and executive functioning and may have implications for intervention development.

The neural substrates of intelligence represent a fundamental but largely uncharted topic in human developmental neuroscience. Prior neuroimaging studies have identified modest but highly dynamic associations between intelligence and cortical thickness (CT) in childhood and adolescence. In a separate thread of research, quantitative genetic studies have repeatedly demonstrated that most measures of intelligence are highly heritable, as are many brain regions associated with intelligence. In the current study, we integrate these 2 streams of prior work by examining the genetic contributions to CT–intelligence relationships using a genetically informative longitudinal sample of 813 typically developing youth, imaged with high-resolution MRI and assessed with Wechsler Intelligence Scales (IQ). In addition to replicating the phenotypic association between multimodal association cortex and language centers with IQ, we find that CT–IQ covariance is nearly entirely genetically mediated. Moreover, shared genetic factors drive the rapidly evolving landscape of CT–IQ relationships in the developing brain.

Down syndrome (DS) is associated with a variety of cognitive impairments, notably memory impairments. Due to the high prevalence rates of early-onset dementia associated with DS, it is imperative to understand the comprehensive development of memory impairments beginning in childhood and into adulthood, as this may help researchers identify precursors of dementia at earlier stages of development and pinpoint targets for memory intervention. The current paper provides a systematic, developmentally focused review of the nature of memory difficulties in DS across the lifespan. Specifically, this review summarizes what is known about long-term, short-term, and working memory abilities (distinguishing between verbal and nonverbal modalities) in DS, compared to both mental age-matched typically developing peers and individuals with other forms of intellectual disability (ID) at three developmental stages (i.e., preschool, adolescence, and adulthood). Additionally, this review examines the degree of impairment reported relative to typically developing mental age-matched peers in the existing literature by examining effect size data across memory domains as a function of age. With few exceptions, memory abilities were impaired across the lifespan compared to mental age-matched typically developing peers. Relative to other groups with ID, research findings are mixed. Our review of the literature identified a scarcity of memory studies in early childhood, particularly for STM and WM. In adulthood, research was limited in the LTM and WM domains and very little research has compared memory abilities in older adults with DS to those with typical development. Looking to the future, longitudinal studies could provide a better understanding of the developmental trajectory of memory abilities in DS, and the possible associations between memory abilities and real-world functioning. This research could ultimately inform interventions to improve independence and overall quality of life for those with DS and their families. Electronic supplementary material The online version of this article (10.1186/s11689-017-9220-y) contains supplementary material, which is available to authorized users.

OBJECTIVE The prevalence of comorbid autism spectrum disorder (ASD) in children with Down syndrome (DS) is estimated to be around 16%. This study aims to fill gaps in the literature by describing developmental and behavioral phenotypes in this group relative to those with DS or ASD in isolation. METHODS Participants included 173 children (Mage = 73 months) with ASD, DS, or DS + ASD. Two 3 × 2 repeated-measures analyses of variance were completed with between-subject factors of the diagnostic group (DS, ASD, and DS + ASD) and within-subject factors of cognitive performance (verbal and nonverbal developmental quotient [DQ]) or ASD symptoms (social affect [SA] and restricted and repetitive behaviors [RRBs]). RESULTS Significant group-by-scale interactions were found, and pairwise comparisons revealed that for verbal DQ, DS + ASD < DS, ASD, whereas for nonverbal DQ, DS + ASD < DS < ASD. For SA, DS < DS + ASD < ASD, whereas for RRB, DS, DS + ASD < ASD. CONCLUSION Findings suggest greater cognitive impairment in DS + ASD on both verbal and nonverbal measures. Despite these significant cognitive challenges, ASD symptoms appeared less severe in DS + ASD relative to peers with ASD in isolation, although SA symptoms were elevated over DS-only. This unique DS + ASD presentation has important implications for early identification and intervention. Given previous research suggesting relative social strengths in DS and less severe ASD symptoms documented in this study, future research may benefit from investigating different aspects of SA (i.e., components related to reciprocal social interaction vs. social communication) in those with DS + ASD to more clearly delineate the social phenotype in this group and potentially inform intervention efforts.

Aim: Sensory processing impairments are well characterized in children with neurodevelopmental disorders, particularly autism, and have been associated with maladaptive behaviors. However, ...

BACKGROUND: Hypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils. METHODS: In this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient’s background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12. RESULTS: During the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse. CONCLUSIONS: In this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.)

The genetics of cortical arealization in youth is not well understood. In this study, we use a genetically informative sample of 677 typically developing children and adolescents (mean age 12.72 years), high-resolution MRI, and quantitative genetic methodology to address several fundamental questions on the genetics of cerebral surface area. We estimate that >85% of the phenotypic variance in total brain surface area in youth is attributable to additive genetic factors. We also observed pronounced regional variability in the genetic influences on surface area, with the most heritable areas seen in primary visual and visual association cortex. A shared global genetic factor strongly influenced large areas of the frontal and temporal cortex, mirroring regions that are the most evolutionarily novel in humans relative to other primates. In contrast to studies on older populations, we observed statistically significant genetic correlations between measures of surface area and cortical thickness (rG= 0.63), suggestive of overlapping genetic influences between these endophenotypes early in life. Finally, we identified strong and highly asymmetric genetically mediated associations between Full-Scale Intelligence Quotient and left perisylvian surface area, particularly receptive language centers. Our findings suggest that spatially complex and temporally dynamic genetic factors are influencing cerebral surface area in our species.SIGNIFICANCE STATEMENTOver evolution, the human cortex has undergone massive expansion. In humans, patterns of neurodevelopmental expansion mirror evolutionary changes. However, there is a sparsity of information on how genetics impacts surface area maturation. Here, we present a systematic analysis of the genetics of cerebral surface area in youth. We confirm prior research that implicates genetics as the dominant force influencing individual differences in global surface area. We also find evidence that evolutionarily novel brain regions share common genetics, that overlapping genetic factors influence both area and thickness in youth, and the presence of strong genetically mediated associations between intelligence and surface area in language centers. These findings further elucidate the complex role that genetics plays in brain development and function.

Neurodevelopmental disorders are highly heritable and associated with spatially-selective disruptions of brain anatomy. The logic that translates genetic risks into spatially patterned brain vulnerabilities remains unclear but is a fundamental question in disease pathogenesis. Here, we approach this question by integrating (i)in vivoneuroimaging data from patient subgroups with known causal genomic copy number variations (CNVs), and (ii) bulk and single-cell gene expression data from healthy cortex. First, for each of six different CNV disorders, we show that spatial patterns of cortical anatomy change in youth are correlated with spatial patterns of expression for CNV region genes in bulk cortical tissue from typically-developing adults. Next, by transforming normative bulk-tissue cortical expression data into cell-type expression maps, we further link each disorder’s anatomical change map to specific cell classes and specific CNV-region genes that these cells express. Finally, we establish convergent validity of this “transcriptional vulnerability model” by inter-relating patient neuroimaging data with measures of altered gene expression in both brain and blood-derived patient tissue. Our work clarifies general biological principles that govern the mapping of genetic risks onto regional brain disruption in neurodevelopmental disorders. We present new methods that can harness these principles to screen for potential cellular and molecular determinants of disease from readily available patient neuroimaging data.

Mosaic trisomy 14 is associated with impaired intellectual functioning, although no study has examined the cognitive-behavioral profile associated with the syndrome. This study provides the first case description of the cognitive-behavioral phenotype associated with mosaic trisomy 14 by contrasting the performance an adolescent female (T14) with a group of females with Down syndrome (DS; n=9). T14 performed below age expectations on most direct assessments and demonstrated weaknesses relative to the DS group on aspects of language, adaptive functioning, and executive functioning. T14 also demonstrated strengths in delayed visual recall and social skills relative to the DS group.

Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social-communicative functioning and repetitive behaviors in a stratified cross-sectional sample of 324 youth with ASD in the absence of intellectual disability, and 438 TD youth (aged 4-29 years). An age-by-group interaction emerged indicating that TD youth exhibited age-related improvements in social-communication scores while the ASD group demonstrated age-related declines in these scores. This suggests that adolescents/adults with ASD may fall increasingly behind their same-age peers in social-communicative skills.

Background Down syndrome is associated with poor sleep but little is known about its neural correlates. Aims The current research compared brain morphometry in youth with Down syndrome with parent-reported sleep problems (DS-S) to peers with Down syndrome (DS) and typical development (TD) without parent-reported sleep problems matched on age (M = 15.15) and sex ratio (62 % female). Methods and procedures Magnetic resonance imaging was completed on a 3 T scanner. Participants were stratified into groups based on parent-report: DS-S (n = 17), DS (n = 9), TD (n = 22). Brain morphometry, processed with the FreeSurfer Image Analysis Suite, was compared across groups. In addition, the co-occurrence of medical conditions in the DS groups was examined. Outcomes and results Youth with DS-S had reduced total, frontal, parietal, and temporal brain volumes relative to DS and TD peers. They also had higher rates of congenital heart defects than the DS-only group; however, this comorbidity did not appear to account for morphometry differences. Conclusions and implications Parent-reported sleep problems in DS appear to relate to global and localized volume reductions. These preliminary results have implications for understanding the neural correlates of poor sleep in DS; they also highlight the importance of examining relations between sleep and other medical comorbidities.

Objectives: Past research suggests that youth with sex chromosome aneuploidies (SCAs) present with verbal fluency deficits. However, most studies have focused on sex chromosome trisomies. Far less is known about sex chromosome tetrasomies and pentasomies. Thus, the current research sought to characterize verbal fluency performance among youth with sex chromosome trisomies, tetrasomies, and pentasomies by contrasting how performance varies as a function of extra X number and X versus Y status. Methods: Participants included 79 youth with SCAs and 42 typically developing controls matched on age, maternal education, and racial/ethnic background. Participants completed the phonemic and semantic conditions of a verbal fluency task and an abbreviated intelligence test. Results: Both supernumerary X and Y chromosomes were associated with verbal fluency deficits relative to controls. These impairments increased as a function of the number of extra X chromosomes, and the pattern of impairments on phonemic and semantic fluency differed for those with a supernumerary X versus Y chromosome. Whereas one supernumerary Y chromosome was associated with similar performance across fluency conditions, one supernumerary X chromosome was associated with relatively stronger semantic than phonemic fluency skills. Conclusions: Verbal fluency skills in youth with supernumerary X and Y chromosomes are impaired relative to controls. However, the degree of impairment varies across groups and task condition. Further research into the cognitive underpinnings of verbal fluency in youth with SCAs may provide insights into their verbal fluency deficits and help guide future treatments. (JINS, 2018, 24, 917–927)

In this review, we summarize current knowledge and hypotheses on the nature of social abnormalities in autism spectrum disorder (ASD) and Williams syndrome (WS). Social phenotypes in ASD and WS appear to reflect analogous disruptions in social cognition, and distinct patterns of social motivation, which appears to be reduced in ASD and enhanced in WS. These abnormalities likely originate from heterogeneous vulnerabilities that disrupt the interplay between domain-general and social domain-specific cognitive and motivational processes during early development. Causal pathways remain unclear. Advances and research gaps in our understanding of the social phenotypes in ASD and WS highlight the importance of (1) parsing the construct of sociability, (2) adopting a developmental perspective, (3) including samples that are representative of the spectrum of severity within ASD and WS in neuroscientific research, and (4) adopting transdiagnostic treatment approaches to target shared areas of impairment across diagnostic boundaries.