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Importance: Autistic adults experience suboptimal health outcomes. Likewise, attention-deficit/hyperactivity disorder (ADHD) is linked to poor health outcomes in the general population, yet little is known about co-occurring ADHD and its links with poor health outcomes among autistic adults., Objective: To determine the prevalence of ADHD and ADHD medication prescriptions and to examine associations between health outcomes and both ADHD co-occurrence and ADHD medication prescriptions among autistic adults., Design, Setting, and Participants: Population-based cohort study of US Medicaid-enrolled adults aged 18 years and older, including autistic adults with and without co-occurring intellectual disability (ID), adults with ID without autism, and adults from a random sample of Medicaid-enrolled individuals from 2008 to 2019. Analyses were completed September 2023 to September 2024., Exposures: Autism, ADHD, and ID using validated algorithms from the Chronic Conditions Warehouse., Main Outcomes and Measures: Prevalence rates of co-occurring ADHD, ADHD medication prescriptions, substance use, cardiovascular conditions, injury in autism without ID, ID without autism, autism with ID, and the general population., Results: The study included 3 506 661 patients (mean [SD] age, 33.5 [15.6] years; 1 854 892 [52.9%] female; 702 694 [20.0%] Black, 587 048 [16.7%] Hispanic, and 1 786 703 [60.0%] White). Compared with the general Medicaid-enrolled population (1 846 102 patients), which had 49 523 patients (2.7%) with co-occurring ADHD diagnoses, this study found elevated rates of ADHD in autism without ID (280 195 patients [26.7%]; prevalence ratio [PR], 5.1; 95% CI, 4.4-5.9), autism with ID (261 061 patients [40.2%]; PR, 6.8; 95% CI, 6.0-7.7), and ID without autism (1 119 303 patients [19.0%]; PR, 4.4; 95% CI, 4.0-5.0). A total of 117 704 adults (26.6%) with ADHD received an ADHD medication prescription. The study identified that rates of substance use were higher among clinical groups with co-occurring ADHD. For example, 9886 of 74 675 autistic adults with ADHD (13.2%) had substance use disorder, compared with 11 782 of 205 520 autistic adults with no ADHD (5.7%). ADHD diagnoses were associated with higher rates of all health outcomes, regardless of group. Substance use was higher in both ID groups with ADHD diagnoses and ADHD medications, whereas injury and cardiovascular condition rates were lower in all ADHD groups who received ADHD medications., Conclusions and Relevance: In this cohort study of Medicaid-enrolled adults, autistic adults experienced high rates of co-occurring ADHD and were more likely to receive ADHD medication prescriptions than adults in the general population. Negative health outcome rates are higher among autistic people with co-occurring ADHD, although ADHD medication prescriptions are associated with lower rates of negative health outcomes. Treating ADHD may improve health among autistic adults.

Evidence is growing for a link between parkinsonism, or the motor symptoms associated with Parkinson's Disease and autism. However, research to date has yet to examine whether the presence of these motoric symptoms impacts critical adult outcomes in autism. Therefore, the current study utilized a screening measure to bifurcate a relatively large (n = 379) sample of middle and older age autistic adults (40-83 years) into parkinsonism screen positive (n = 119) versus parkinsonism screen negative (n = 260) groups in order to compare them on broad metrics of daily living skills and subjective quality of life as well as non-motoric features linked to parkinsonism, namely memory problems, sleep quality, and depression symptoms. Overall, co-occurring parkinsonism was linked with lower subjective quality of life, more memory problems, lower sleep quality, and greater depression symptoms in autistic adults. Taken together, these findings implicate an important co-occurring motoric phenotype in middle and older adulthood for autistic people that could have significant real-world impacts yet has been largely neglected in the extant literature to date., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Lay Abstract: Finding a job can be hard for autistic adults. No studies have been completed that look into whether having difficulties learning and troubles finding a job are related in this population. The current study did so by evaluating the Learning Needs Screening Tool, a measure of learning challenges used in vocational rehabilitation settings, or places meant to help people find work. A total of 401 autistic adults completed this study online. Specifically, the study evaluated (a) the characteristics of the Learning Needs Screening Tool, including the relationships between questions that ask about similar learning challenges, and (b) the ability of the measure to relate to real-world outcomes that are associated with learning difficulties, namely prior special education receipt and difficulties finding a job. Evaluation of the questions asked on the Learning Needs Screening Tool revealed that they were highly related and that learning difficulties fell into different categories. Fifty-six percent of the people in the study showed learning challenges on the measure. People who were identified as having learning difficulties on the Learning Needs Screening Tool had higher rates of receiving special education services in the past and lower rates of current employment. These results suggest that the Learning Needs Screening Tool may help to identify autistic job seekers who have learning difficulties and may have more challenges finding a job., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lay Abstract: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lay Abstract: Previous research has shown that girls/women are diagnosed later than boys/men with autism. Individuals who are diagnosed later in life, especially girls/women, have greater anxious and depressive symptoms. Previous research has been limited due to narrow inclusionary criteria for enrollment in studies. The present study uses two samples-one clinic-based, large "real-world" sample and another research-based sample with strict criteria for autism diagnosis-to understand the relationships between diagnostic age, sex assigned at birth, and symptoms of anxiety/depression. In both samples, those who were diagnosed later had greater anxious/depressive symptoms, and anxiety was not predicted by sex. In the clinic-based but not research-based sample, those assigned female at birth were diagnosed later than those assigned male at birth. In the clinic-based sample only, individuals assigned female at birth and who were later diagnosed experienced greater symptoms of anxiety/depression compared to those assigned male who benefited from earlier diagnostic timing. Within the research-based sample, those assigned female at birth had greater depressive symptoms than those assigned male. These findings highlight the importance of timely identification of autism, especially for girls/women who are often diagnosed later. Community-based samples are needed to better understand real-world sex-based and diagnostic age-based disparities in mental health., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Camouflaging involves the masking of autism traits, potentially creating an outer impression of "non-autisticness." Although associations of camouflaging with anxiety and depression in autistic adults are widely reported, factors that mediate these associations are unclear. We examined two potential mediators of the association between camouflaging and anxiety/depression: perceived stress and emotion regulation (ER) challenges., Methods: Seven hundred eighty-seven autistic adults (18.2-78.2 years) recruited through 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 ER challenges. Four moderated mediation models were tested. In all models the independent variable was CAT-Q total score, and the moderator variable was sex designated at birth. The dependent variable was depressive or anxious symptomatology, and the mediator variable was perceived stress or ER challenges., Results: We found that more camouflaging, increased ER challenges, and higher levels of perceived stress were associated with greater depressive and anxious symptomatology. We also found that perceived stress and ER challenges 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., Conclusion: We contextualize the findings within the broader literature on camouflaging as a response to stigma and other facets of minority stress. We discuss how the results of this study support the idea that the day-to-day stress of living in a neurotypical world, the cognitively demanding nature of camouflaging, and the constraints that camouflaging place on autistic people's behaviors in social contexts (e.g., contributing to suppressing ER strategies such as stimming), create a cycle that contributes to elevated rates of anxiety and depression in autistic people., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Menopause is a normal part of aging and in the general population is associated with chronic conditions that impact health, mortality, and well-being. Menopause is experienced differently by autistic individuals, although no studies have investigated this topic in a large sample. The purpose of this study was to investigate rates of, and factors associated with symptomatic menopause among autistic individuals and to identify the prevalence of co-occurring conditions in symptomatic individuals. We included autistic females aged 35-70 years enrolled for 10 + months in 2014-2016 Medicare and/or Medicaid (n = 26,904), excluding those with gender dysphoria. Those with symptomatic menopause were compared to a non-symptomatic reference group on demographic, enrollment characteristics, and co-occurring conditions through logistic regression. Approximately 4% of publicly-insured autistic females aged 46-70 years had symptomatic menopause in their medical records. Intellectual disability was associated with a lower likelihood of symptomatic menopause, and being Medicare-enrolled or dual-enrolled was associated with higher likelihood of having symptomatic menopause recorded. In adjusted models, rates of ADHD, anxiety and depressive disorders, headache/migraine, altered sensory experiences, altered sexual function, and sleep disturbance were significantly higher in the symptomatic menopause sample compared to the reference group. More work to better support autistic women in discussing menopausal symptoms and co-occurring conditions with primary care providers is needed, particularly among those for whom self-report of symptoms are more challenging to ascertain. Factors associated with specific types of health care coverage warrant greater investigation to support better identification., (© 2024. The Author(s).)

Many commonly used prescription and over-the-counter medicines have potent anticholinergic (AC) effects. Among older adults, AC medications are associated with cognitive impairment and risk for cognitive disorders, including Alzheimer's disease. Collectively, the impact of AC medications is known as anticholinergic cognitive burden (ACB). Because of the high rates of co-occurring medical and psychiatric conditions, autistic adults may have high AC exposure and, thus, may experience elevated ACB. However, no research has characterized AC exposure or examined its associations with cognitive outcomes in autistic adults. Autistic adults (40-83 years) recruited via Simons Powering Autism Research's (SPARK) Research Match service self-reported their medication use (N = 415) and memory complaints (N = 382) at Time (T)1. At T2, 2 years later, a subset of T1 participants (N = 197) self-reported on decline in cognition. Medications were coded using two scales of AC potency. A high proportion (48.2%-62.9%, depending upon the AC potency scale) of autistic adults reported taking at least one medication with AC effects, and 20.5% to 26.5% of autistic adults reported clinically-relevant levels of AC medication (potency ≥3). After controlling for birth-sex, and age, hierarchical linear regression models showed total ACB scores and AC potency values of ≥3 predicted greater memory complaints. Logistic regression models showed that AC medicines at T1 were associated with self-reported cognitive decline at follow-up 2 years later. Understanding AC medications-including potentially earlier AC polypharmacy-and their impacts on cognition (e.g., dementia risk) in autistic adults is warranted., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

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 a subset of 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 indicate the need for research on phenotype-driven vocational rehabilitation strategies as well as workplace psychoeducation/accommodations to support vocational outcomes for autistic adults., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cognitive flexibility differences are common for autistic individuals and have an impact on a range of clinical outcomes. However, there is currently a lack of well validated measurement tools to assess flexibility in adulthood. The Flexibility Scale was originally designed as a parent-report measure of real-world flexibility challenges in youth. The original Flexibility Scale provides a total score and five subscales: Routines and Rituals, Transitions and Change, Special Interests, Social Flexibility, and Generativity. In this study, we evaluate the factorial validity of the Flexibility Scale as a self-report (Flexibility Scale Self Report) measure of cognitive flexibility, adapted from the original Flexibility Scale, for use by autistic adults. This study includes both a primary sample (n = 813; mean age = 40.3; 59% female) and an independently recruited replication sample (n = 120; mean age = 32.8; 74% female) of individuals who completed the Flexibility Scale Self Report. The analysis consisted of an initial confirmatory factor analysis (CFA) of the original Flexibility Scale structure, followed by exploratory factor analysis (EFA) and factor optimization within a structural equation modeling framework to identify the optimal structure for the questionnaire in adults. The identified structure was then replicated through CFA in the replication sample. Our results indicate an alternative optimal scale structure from the original Flexibility Scale, which includes fewer items, and only three (Routines/Rituals, Transitions and Change, Special Interests) of the five subscales contributing to the flexibility total score. Comparisons revealed no structural differences within the scale based on sex assigned at birth. Here the Generativity and Social Flexibility scales are treated as independent but related scales. The implications for measurement of cognitive flexibility in clinical and research settings, as well as theoretical underpinnings are discussed., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10-77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (> 33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female-Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item-response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related "insider" language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although disparities in mental health and subjective quality of life (QoL) 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 nonautistic individuals to be from groups with other minority identities, including sexual minorities (i.e., sexual orientations such as asexual, bisexual, gay). 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 QoL for sexual minority compared with heterosexual autistic adults., Methods: Participants were 651 autistic adults aged 18.5 to 83.3 years recruited through Simons Powering Autism Research's Research Match. All participants resided in the United States. Participants completed surveys online, including measures of anxious and depressive symptomatology, perceived stress, and subjective QoL. Participants reported their sexual orientation and other sociodemographic variables., Results: A large proportion of autistic adults reported a sexual minority identity (41.2%), and a diversity of sexual identities was reported. Sexual minority autistic adults reported poorer mental health and lower subjective QoL across all assessed domains relative to heterosexual autistic adults., Conclusion: Understanding factors that may be associated with poorer mental health and decreased subjective QoL in autistic adults is critical and has been identified as a research priority by autistic stakeholders. The findings reported here underscore the need to examine mental health and subjective QoL disparities among autistic individuals within a societal context, taking into consideration the potential of intersecting minority identities and increased social stressors, as these added stressors may increase risks for poorer outcomes., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Poor sleep can have a significant impact on physical health and well-being. Sleep problems are common among autistic children, but less 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 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, assigned female sex at birth 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, and daytime dysfunction. Depression symptoms did not contribute significantly to any of the models of sleep quality. However, utilizing government support mechanisms (such as social security) contributed to the model of sleep efficiency. Age contributed little to models of sleep quality, whereas perceived stress and psychotropic medication use contributed to some but not all aspects of sleep. 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 everyday effects for autistic people of all ages., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Very little is known about autistic adults as they age. Early evidence suggests a potentially high risk for dementia and atypical cognitive decline in autistic middle and older age adults. Research in the general population indicates that self-reported cognitive decline may predict future dementia earlier than performance-based measures. Nevertheless, self-report dementia screeners have not been used to date in autism research. In a sample of middle and older age autistic adults (N = 210), participants completed a self-rated dementia screener, the AD8, to describe the rate of cognitive decline, examine associations of cognitive decline with age, educational level, sex designated at birth, and autistic traits, and document the psychometrics of a dementia screener in autistic adults. We found high rates of cognitive decline with 30% of the sample screening positive. The most common symptoms were declining interest in leisure activities, and increases in everyday problems with thinking, memory, and judgment. There was evidence that autistic individuals designated female at birth may be more vulnerable to cognitive decline than autistic individuals designated male at birth. Notably, reports of cognitive decline did not vary by age or educational level. Modestly elevated autistic traits were found in those screening positive versus negative for cognitive decline. Finally, the dementia screener showed good psychometrics, including convergent validity with an independent measure of current memory problems. These results could signal an emerging public health crisis in autistic adults as they age, and support the potential utility of self-report measures for early screening for cognitive decline in this population., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)

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., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Lay Abstract: Social support can take many forms, such as practical help, time spent socially with others, or the satisfaction with personal relationships. Social support is known to affect quality of life (QoL) in both non-autistic older and autistic young adults. QoL reflects how satisfied an individual is with their life either overall or in a certain area. We know little about middle-aged and older autistic adults' experiences of social support or QoL. In this study, 388 adults aged 40-83 years old, completed online questionnaires asking about background such as age and sex, depression and anxiety symptoms, QoL (physical, psychological, social, environmental, and autism-specific), and different types of social support. Even after taking into account background, depression, and anxiety, social support was important for individuals' QoL. To our knowledge this is the first paper to examine the relationship between social support and QoL in middle-aged and older autistic adults. Improving social support may have a significant impact on the QoL of older autistic adults. Future studies should examine whether age-related changes in social support (size, content, and arrangement of social networks) that are common in non-autistic aging, also occur among older autistic adults.

Lay Abstract: Outcomes 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.

Objective : Selective or "picky" eating (SE) refers to rejection of a wide range of familiar and unfamiliar foods based on aversions to their sensory properties. When severe, SE can cause symptoms of avoidant/restrictive food intake disorder (ARFID), including weight loss, nutritional deficiencies, and/or psychosocial impairment. SE is highly prevalent in autism spectrum disorder (ASD) compared to both typical development and other developmental disorders. A possible explanation for the high prevalence of SE in ASD is the effect of core ASD symptoms, repetitive/restrictive behaviors (e.g., rigidity), and sensory sensitivity on feeding behaviors. These traits are found not only in ASD but also in other clinical groups and the general population, albeit often at subclinical levels. Identifying mechanisms of SE across various populations is critical to inform intervention approaches. Methods : In 263 unselected children ages 5-17, 534 unselected college students ages 18-22, 179 children with anxiety/obsessive spectrum disorders ages 5-17, and 185 children with ASD ages 4-17, we explored the unique contributions of sensory (i.e., oral texture and olfactory) sensitivities and rigidity as predictors of self/parent-reported SE. Results : In each sample, rigidity and oral texture sensitivity, controlling for olfactory sensitivity, age, and gender, emerged as significant, independent predictors of SE. Conclusions : This is the first study to highlight the importance of cognitive/behavioral rigidity to SE, and one of the first to illustrate the domain-specificity of the relationship between sensory sensitivity and SE.

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., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

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., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity., (© 2022. The Author(s).)

Based on parent questionnaires, we demonstrate the presence of an eating pattern among children with autism spectrum disorder (ASD) that is characterized by both food selectivity and eating in the absence of hunger. Children with ASD were categorized as engaging in eating patterns of selective overeating, selective eating only, overeating only, or typical eating. Group differences were found in the areas of diet composition, body mass index, and behavioral flexibility. Both the selective overeating group and selective eating only group were prone to favor calorie-dense, nutrient-deficient diets as compared to other groups. Eating groups also presented with differing profiles of everyday behavioral flexibility. These results suggest that selective overeating in ASD may present unique challenges and require tailored interventions., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Lay Abstract: Executive functions are often impaired in autistic people and relate to important outcomes such as mental health, success in school and work, and quality of life. Evaluating executive functions helps autistic people, clinicians, and families identify targets for external supports and skill building. Youth self-report of executive function has not been studied, yet we know that self-report from autistic youth is key to understanding other cognitive/behavioral phenomena in autism such as anxiety, obsessions/compulsions, sensory sensitivities, and repetitive behaviors. We investigated self- and parent-report of executive function problems in 197 autistic youth without intellectual disability (ages 11-18 years), including the magnitude and profiles of executive function problems autistic youth report across subdomains of executive function. We compared autistic self-report with that of 114 youth with attention deficit hyperactivity disorder without intellectual disability and 197 neurotypical youth. We found that autistic youth report significant executive function problems compared to neurotypical youth and a distinctive profile of challenges in comparison to attention deficit hyperactivity disorder youth. Parents and their autistic children diverged regarding the magnitude of the youth's executive function difficulties, but both identify inflexibility as the most impaired executive function subdomain. Autistic youth and their parents were somewhat more concordant in their report of executive function problems than youth with attention deficit hyperactivity disorder and their parents, but only showed moderate concordance at best. These findings elevate the importance of asking autistic youth directly about their executive functioning when engaging them in assessment and intervention, or researching executive functions in autism.

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.

Lay Abstract: Autistic adults without a suspected intellectual disability reported several motor features such as having tremors, and stiffness in one's legs which are considered to be part of a complex of motor features called parkinsonism. This so-called parkinsonism was remarkably prevalent in middle-aged and older autistic adults in two independent studies (Dutch study: 50-81 years, 183 males, 113 females, all adulthood diagnoses; the USA study: 50-83 years, 110 females, 109 males, majority adulthood diagnosis). Parkinsonism can be part of the progressive motor disease-Parkinson's disease. Therefore, it is important that future studies, including in-person neurological assessment, determine if (and if so, why) autistic adults who report these motor features are at increased risk for developing Parkinson's disease.

Lay Abstract: Adaptive functioning refers to skills that are vital to success in day-to-day life, including daily living (e.g. grocery shopping, food preparation, transportation use), communication (e.g. verbal expression of needs), and socialization skills (e.g. interpersonal skills, including expressing and recognizing emotions, and understanding turn-taking in conversation). Among autistic individuals without intellectual disability, adaptive functioning is not commensurate with intellectual ability (IQ), and instead a gap exists between these individuals' intellectual ability and their adaptive skills. Further, these autistic individuals show a widening of this gap with increasing age. Existing studies of the gap between IQ and adaptive functioning have studied predominantly male samples. Thus, we do not know if the gap also exists in autistic females. We therefore looked at adaptive functioning and the gap between IQ and adaptive functioning in a large sample of autistic girls and boys without intellectual disability. To disentangle effects of group (autistic vs typically developing) from effects of sex (girls vs boys), we compared autistic girls and boys to one another as well as to their same-sex typically developing peers. Analyses took into consideration differences in IQ between autistic and typically developing youth. We found autistic girls, like autistic boys, show lower adaptive functioning than their same-sex typically developing peers. Results underscore the need to evaluate adaptive functioning in autistic individuals without intellectual disability and to provide necessary supports. The large gap between intellectual ability and socialization skills, in particular, may be of critical importance in improving our understanding of outcomes and mental health difficulties among autistic females.

Lay Abstract: Although "picky" eating is well documented in autism spectrum disorder, emotional eating has rarely been investigated. This study examined emotional over- and under-eating based on parent ratings of these behaviors in 4- to 17-year-old children with autism spectrum disorder ( n  = 190) as compared to same-age typically developing children ( n  = 119). Children with autism spectrum disorder were rated as exhibiting both more emotional over-eating and more emotional under-eating behaviors than their typically developing peers. Furthermore, while sex differences in these emotional eating behaviors were not observed in the typically developing children, girls with autism spectrum disorder were rated as experiencing more emotional over-eating behaviors than boys with autism spectrum disorder. Finally, among all children with autism spectrum disorder, emotional over-eating was linked with increased consumption of sweet foods and decreased consumption of vegetables. These findings have implications for better understanding eating habits in children with autism spectrum disorder and suggest that emotional eating behaviors might have both immediate and downstream health impacts.

Females with autism spectrum disorder (ASD) have been long overlooked in neuroscience research, but emerging evidence suggests they show distinct phenotypic trajectories and age-related brain differences. Sex-related biological factors (e.g., hormones, genes) may play a role in ASD etiology and have been shown to influence neurodevelopmental trajectories. Thus, a lifespan approach is warranted to understand brain-based sex differences in ASD. This systematic review on MRI-based sex differences in ASD was conducted to elucidate variations across the lifespan and inform biomarker discovery of ASD in females We identified articles through two database searches. Fifty studies met criteria and underwent integrative review. We found that regions expressing replicable sex-by-diagnosis differences across studies overlapped with regions showing sex differences in neurotypical cohorts. Furthermore, studies investigating age-related brain differences across a broad age-span suggest distinct neurodevelopmental patterns in females with ASD. Qualitative comparison across youth and adult studies also supported this hypothesis. However, many studies collapsed across age, which may mask differences. Furthermore, accumulating evidence supports the female protective effect in ASD, although only one study examined brain circuits implicated in "protection." When synthesized with the broader literature, brain-based sex differences in ASD may come from various sources, including genetic and endocrine processes involved in brain "masculinization" and "feminization" across early development, puberty, and other lifespan windows of hormonal transition. Furthermore, sex-related biology may interact with peripheral processes, in particular the stress axis and brain arousal system, to produce distinct neurodevelopmental patterns in males and females with ASD. Future research on neuroimaging-based sex differences in ASD would benefit from a lifespan approach in well-controlled and multivariate studies. Possible relationships between behavior, sex hormones, and brain development in ASD remain largely unexamined., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that occur during puberty, a critical question is whether this treatment impacts neurodevelopment. Methods: A Delphi consensus procedure engaged 24 international experts in neurodevelopment, gender development, puberty/adolescence, neuroendocrinology, and statistics/psychometrics to identify priority research methodologies to address the empirical question: is pubertal suppression treatment associated with real-world neurocognitive sequelae? Recommended study approaches reaching 80% consensus were included in the consensus parameter. Results: The Delphi procedure identified 160 initial expert recommendations, 44 of which ultimately achieved consensus. Consensus study design elements include the following: a minimum of three measurement time points, pubertal staging at baseline, statistical modeling of sex in analyses, use of analytic approaches that account for heterogeneity, and use of multiple comparison groups to minimize the limitations of any one group. Consensus study comparison groups include untreated transgender youth matched on pubertal stage, cisgender (i.e., gender congruent) youth matched on pubertal stage, and an independent sample from a large-scale youth development database. The consensus domains for assessment includes: mental health, executive function/cognitive control, and social awareness/functioning. Conclusion: An international interdisciplinary team of experts achieved consensus around primary methods and domains for assessing neurodevelopmental effects (i.e., benefits and/or difficulties) of pubertal suppression treatment in transgender youth., Competing Interests: No competing financial interests exist., (© Diane Chen et al. 2020: Published by Mary Ann Liebert, Inc.)

Executive functioning is thought to contribute to adaptive behavior skills development in individuals with autism spectrum disorder (ASD). However, supporting data are largely based on caregiver reports of executive functioning. The current study evaluated whether performance-based measures of executive functioning (working memory and inhibition) explained unique variance in parent-reported adaptive functioning among youth with ASD without an intellectual disability. Both spatial and verbal working memory were associated with adaptive functioning, particularly communication and daily living skills. Our findings demonstrate a robust relationship between working memory and adaptive functioning that translates across different measurement modalities. This preliminary study highlights that targeting executive functioning may be a critical component of an adaptive function training program.

Background: Characterizing puberty in autism spectrum disorder (ASD) is critical given the direct impacts of pubertal progression on neural, cognitive, and physical maturation. Limited information is available about the utility and parent-child concordance of the self-report and parent-report Pubertal Development Scale (PDS) in ASD, an economical and easily administered measure., Method: The primary aim of this study was to examine the concordance between self-report and parent-report PDS ratings in autistic males and females ages 8-17y compared to typically developing (TD) youth, including using the PDS to derive informant-based estimates of adrenal and gonadal development. We hypothesized that there would be greater parent-youth discrepancies in pubertal ratings among autistic males. Our second aim was exploratory; we examined whether individual characteristics impact PDS concordance and hypothesized that lower intellectual and adaptive skills, higher autistic traits, and reduced self-awareness/monitoring would correlate with lower concordance., Results: There were no significant diagnostic group differences in parent-youth concordance for overall PDS scores among males and females. Autistic males had significantly lower inter-item agreement with their parents than TD males and had lower agreement for both adrenal and gonadal aspects of pubertal maturation (adrenal κ=.48; gonadal κ=.55)., Conclusions: The PDS is a feasible measure in ASD. Greater parent-youth discrepancies in autistic males may be due to reduced parental awareness or reduced insight into pubertal maturation among autistic males. Future research is needed to further elucidate individual and/or environmental characteristics that influence youth- and parent-reported PDS scores, including differences in self-perception and insight., Competing Interests: Conflicts of Interest: The authors report no conflicts of interest.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data., Methods: Structural T 1 -weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures)., Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood., Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Little is known about the impact of aging with Autism Spectrum Disorder on theory of mind (ToM). While ToM difficulties appear to abate with age in older autistic populations, this has yet to be explored in the Broad Autism Phenotype (BAP). The current study examined ToM performance among younger (n = 49, aged 18-46) and older adults (n = 47, aged 60-91) who were classified as on the BAP (younger n = 18; older n = 21) or not (younger n = 31; older n = 26) using the BAP Questionnaire. ToM was assessed using the ecologically valid Strange Stories Film Task (SSFT) and the dynamic Happé-Frith Triangle Animations task (TA). A 2 × 2 analysis of variance examined the effects of autistic traits (BAP vs. non-BAP) and age (young vs. old). For both SSFT and TA, results showed autistic trait main effects on task performance (non-BAP > BAP). Age main effects were observed for some but not all metrics on TA (younger better than older), with no differences in SSFT. An interaction of autistic traits and age was observed in TA Intentionality, with younger non-BAP and younger BAP performing similarly but older non-BAP performing better than older BAP. Results show that younger and older adults with elevated autistic traits show poorer ToM performance. Despite ToM difficulties being common in later life in the general population, this effect was not observed when using a ToM task designed to reflect real-world scenarios. However, results suggest that autistic traits and age could interact to increase risk for poor ToM performance in older adults who endorse elevated autistic traits. Autism Res 2020, 13: 751-762. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The behaviors and characteristics commonly found in autism spectrum disorders have been linked to differences in understanding social situations. Similar difficulties have also been found in older age. We assessed social understanding in younger and older adults from the general population. Both younger and older adults who report more autism-like characteristics experience more difficulties with social understanding. However, few differences were found between younger and older adults., (© 2019 International Society for Autism Research, Wiley Periodicals, Inc.)

Behavioral traits associated with various forms of psychopathology are conceptualized as dimensional, varying from those present in a frank disorder to subclinical expression. Demonstrating links between these behavioral traits and neurobiological indicators, such as brain structure, provides one form of validation for this view. However, unlike behavioral dimensions associated with other forms of psychopathology (e.g., autism spectrum disorder, attention deficit hyperactivity disorder, antisocial disorders), eating disorder traits have not been investigated in this manner in spite of the potential that such an approach has to elucidate etiological mechanisms. Therefore, we examined for the first time neural endophenotypes of Anorexia Nervosa and Bulimia via dimensional traits (measured using the Eating Disorders Inventory-3) in a large subclinical sample of young adults (n = 456 and n = 247, respectively; ages = 18-22 years) who each provided a structural magnetic resonance imaging scan. Cortical thickness was quantified at 81,924 vertices across the cortical surface. We found: 1) increasing eating disorder traits correlated with thinner cortex in the insula and orbitofrontal cortex, among other regions, and 2) using these regions as seeds, increasing eating disorder trait scores negatively modulated structural covariance between these seed regions and other cortical regions linked to regulatory and sensorimotor functions (e.g., frontal and temporal cortices). These findings parallel those found in the clinical literature (i.e., thinner cortex in these food-related regions in individuals with eating disorders) and therefore provide evidence supporting the dimensional view of behavioral traits associated with eating disorders. Extending this approach to genetic and neuroimaging genetics studies holds promise to inform etiology.

Cognitive and behavioral flexibility are important predictors of adaptive behavior in school-age autistic youth. While prior research has utilized broad measures of flexibility, the current study uses the multi-dimensional Flexibility Scale-Revised to examine which specific flexibility skills relate to adaptive functioning. Through parent-report measures on 216 autistic youth, flexibility explained 22.2% of variance in adaptive socialization skills (p < 0.001). Specifically, Social Flexibility accounted for significant variance in adaptive socialization skills, while Transitions/Change approached significance. In exploratory analyses, flexibility explained 11.5% of variance in Communication skills (p < 0.001). This pattern remained after controlling for co-occurring ADHD symptoms. The current study helps to refine the relationship between flexibility and adaptive behavior, which may ultimately help to inform more targeted interventions.

Objective: Structural brain differences are found in adults and children with epilepsy, yet pediatric samples have been heterogeneous regarding seizure type, magnetic resonance imaging (MRI) findings, and hemisphere of seizure focus. This study examines whether cortical thickness and surface area differ between children with left-hemisphere focal epilepsy (LHE) and age-matched typically developing (TD) peers. We examined whether age differentially moderated cortical thickness between groups and if cortical thickness was associated with duration of epilepsy, seizure frequency, or neuropsychological functioning., Methods: Thirty-five children with LHE and 35 TD children completed neuropsychological testing and 3T MR imaging. Neuropsychological measures included general intelligence and executive functioning. All MRIs were normal. Surface-based morphometric processing and analyses were conducted using FreeSurfer 6.0. Regression analyses compared age by cortical thickness differences between groups. Correlational analyses examined associations between cortical thickness in these areas with neuropsychological functioning or epilepsy characteristics., Results: Left-hemisphere focal epilepsy displayed decreased cortical thickness bilaterally compared to TD controls across 6 brain regions but no differences in surface area. Moderation analyses revealed quadratic relationships between age and cortical thickness for left frontoparietal-cingulate and right superior frontal regions. Higher performance intelligence quotient (IQ) (PIQ) and verbal IQ (VIQ) and fewer parent reported executive function problems were associated with greater cortical thickness in TD children., Significance: Children with LHE displayed thinner cortex extending beyond the hemisphere of seizure focus. The nonlinear pattern of cortical thickness across age occurring in TD children is not evident in the same manner in children with LHE. These differences in cortical thickness patterns were greatest in children 8-12 years old. Greater cortical thickness was associated with higher IQ and fewer executive control problems in daily activities in TD children. Thus, differences in cortical thickness in the absence of differences in surface area, suggest cortical thickness may be a sensitive proxy of subtle neuroanatomical changes that are related to neuropsychological functioning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

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 ( r G = 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 STATEMENT Over 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., Competing Interests: The authors declare no competing financial interests., (Copyright © 2019 the authors.)

Autism spectrum disorder (ASD) is more prevalent in males than females, but the underlying neurobiology of this sex bias remains unclear. Given its involvement in ASD, its role in sensorimotor, cognitive, and socio-affective processes, and its developmental sensitivity to sex hormones, the cerebellum is a candidate for understanding this sex difference. The current study used resting-state functional magnetic resonance imaging (fMRI) to investigate sex-dependent differences in cortico-cerebellar organization in ASD. We collected resting-state fMRI scans from 47 females (23 ASD, 24 controls) and 120 males (56 ASD, 65 controls). Using a measure of global functional connectivity (FC), we ran a linear mixed effects analysis to determine whether there was a sex-by-diagnosis interaction in resting-state FC. Subsequent seed-based analyses from the resulting clusters were run to clarify the global connectivity effects. Two clusters in the bilateral cerebellum exhibited a diagnosis-by-sex interaction in global connectivity. These cerebellar clusters further showed a pattern of interaction with regions in the cortex, including bilateral fusiform, middle occipital, middle frontal, and precentral gyri, cingulate cortex, and precuneus. Post hoc tests revealed a pattern of cortico-cerebellar hyperconnectivity in ASD females and a pattern of hypoconnectivity in ASD males. Furthermore, cortico-cerebellar FC in females more closely resembled that of control males than that of control females. These results shed light on the sex-specific pathophysiology of ASD and are indicative of potentially divergent neurodevelopmental trajectories for each sex. This sex-dependent, aberrant cerebellar connectivity in ASD might also underlie some of the motor and/or socio-affective difficulties experienced by members of this population, but the symptomatic correlate(s) of these brain findings remain unknown. Clinical Trial Registration: www.ClinicalTrials.gov, NIH Clinical Study Protocol 10-M-0027 (ZIA MH002920-09) identifier #NCT01031407.

Conversation is an important and ubiquitous social behaviour. Individuals with autism spectrum disorder (autism) without intellectual disability often have normal structural language abilities but deficits in social aspects of communication like pragmatics, prosody, and eye contact. Previous studies of resting state activity suggest that intrinsic connections among neural circuits involved with social processing are disrupted in autism, but to date no neuroimaging study has examined neural activity during the most commonplace yet challenging social task: spontaneous conversation. Here we used functional MRI to scan autistic males (n = 19) without intellectual disability and age- and IQ-matched typically developing control subjects (n = 20) while they engaged in a total of 193 face-to-face interactions. Participants completed two kinds of tasks: conversation, which had high social demand, and repetition, which had low social demand. Autistic individuals showed abnormally increased task-driven interregional temporal correlation relative to controls, especially among social processing regions and during high social demand. Furthermore, these increased correlations were associated with parent ratings of participants' social impairments. These results were then compared with previously-acquired resting state data (56 autism, 62 control subjects). While some interregional correlation levels varied by task or rest context, others were strikingly similar across both task and rest, namely increased correlation among the thalamus, dorsal and ventral striatum, somatomotor, temporal and prefrontal cortex in the autistic individuals, relative to the control groups. These results suggest a basic distinction. Autistic cortico-cortical interactions vary by context, tending to increase relative to controls during task and decrease during test. In contrast, striato- and thalamocortical relationships with socially engaged brain regions are increased in both task and rest, and may be core to the condition of autism., (Published by Oxford University Press on behalf of the Guarantors of Brain 2019.)

Background: Autism spectrum disorder (ASD) has been linked with eating- and feeding-related atypicalities, including food neophobia (FN) (refusal to try unfamiliar foods), since its earliest description. Nevertheless, whether associations between ASD traits and FN extend subclinically into the broader population of children and their potential additive health impacts remains unexplored., Objective: We examined ASD-control group differences in FN and ASD trait-FN trait associations, as well as the ability of FN and autistic traits to predict one index of later health-related outcomes [body mass index (BMI)]., Design: Participants in the present study were a large community-based sample of 8- to 11-y-olds (n = 4564), including a relatively small group of children diagnosed with ASD (n = 37). Parents of these 8- to 11-y-old children completed assessments of FN and autistic traits and provided height and weight metrics at 12 y of age., Results: Children with ASD were rated as more food neophobic than their same-age non-ASD peers (2.67 ± 0.83 compared with 2.22 ± 0.73; P < 0.001), and there were subclinical associations between FN and ASD traits (social, communication, and restricted/repetitive behavior) in this community-based sample of children (P < 0.05). Moreover, whereas FN alone predicted lower BMI, the interaction of FN and ASD traits predicted higher BMI (P ≤ 0.01), suggesting that elevated ASD traits in combination with FN exert opposing influences on weight compared with FN alone., Conclusions: These findings implicate clinical and subclinical connections between ASD traits and feeding behaviors that could affect health outcomes and therefore should be further explored in future studies of shared etiology and intervention strategy.

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).

Impairments in social communication (coupled with intact nonsocial language skills) are common in autism spectrum disorder (ASD). However, the neural correlates of these social communication deficits in adolescents and young adults with ASD are not fully understood. The communication checklist self-report (CC-SR) was administered to adolescents and young adults with ASD (n = 52) and typically developing (TD) controls (n = 64) to assess structural-language, pragmatic-language, and social-engagement. One high-resolution T1-weighted structural image was obtained from each participant. FreeSurfer was used to quantify cortical thickness. A main effect of diagnosis, with the ASD group performing worse than the TD group on all three CC-SR scales, and a diagnosis by scale interaction, driven by low social-engagement self-ratings in the ASD group, were found. There were also group differences in the relationship between scores on two of the three CC-SR scales and cortical thickness in multiple regions (pragmatic-language: left rostral frontal; social-engagement: left medial prefrontal). These interactions were driven by poorer self-ratings of language/social skills associated with decreased cortical thickness in the ASD group, while in the TD group worse self-ratings were associated with thicker cortex. Self-ratings of language/social-communication were lower in the ASD than the TD group. Moreover, language/social-communication self-ratings showed a different relationship with cortical thickness for the ASD and TD groups in the left inferior frontal region for pragmatic language ratings and the left medial prefrontal cortex for social engagement ratings. These findings suggest thinner cortex is associated with more impaired pragmatic language and social communication abilities in ASD. Autism Res 2018, 11: 1175-1186. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The present study examines the associations between brain structure and language/social communication ability in adolescents and young adults with autism spectrum disorder (ASD) as compared to neurotypical adolescents and young adults. We utilized thickness of the cerebral cortex as a measure of brain structure, and we found different correlations between language or social communication ability and cortical thickness in distinct regions for the ASD and TD groups. These findings suggest that for regions implicated in language/social communication ability, decreased cortical thickness is associated with more impaired pragmatic language and social communication abilities in ASD., (© 2018 International Society for Autism Research, Wiley Periodicals, Inc.)