Showing papers in "Autism Research in 2022"

Global prevalence of autism: A systematic review update

Abstract: Prevalence estimates of autism are essential for informing public policy, raising awareness, and developing research priorities. Using a systematic review, we synthesized estimates of the prevalence of autism worldwide. We examined factors accounting for variability in estimates and critically reviewed evidence relevant for hypotheses about biological or social determinants (viz., biological sex, sociodemographic status, ethnicity/race, and nativity) potentially modifying prevalence estimates of autism. We performed the search in November 2021 within Medline for studies estimating autism prevalence, published since our last systematic review in 2012. Data were extracted by two independent researchers. Since 2012, 99 estimates from 71 studies were published indicating a global autism prevalence that ranges within and across regions, with a median prevalence of 100/10,000 (range: 1.09/10,000 to 436.0/10,000). The median male‐to‐female ratio was 4.2. The median percentage of autism cases with co‐occurring intellectual disability was 33.0%. Estimates varied, likely reflecting complex and dynamic interactions between patterns of community awareness, service capacity, help seeking, and sociodemographic factors. A limitation of this review is that synthesizing methodological features precludes a quality appraisal of studies. Our findings reveal an increase in measured autism prevalence globally, reflecting the combined effects of multiple factors including the increase in community awareness and public health response globally, progress in case identification and definition, and an increase in community capacity. Hypotheses linking factors that increase the likelihood of developing autism with variations in prevalence will require research with large, representative samples and comparable autism diagnostic criteria and case‐finding methods in diverse world regions over time.

Autism‐related language preferences of English‐speaking individuals across the globe: A mixed methods investigation

Abstract: Over the past two decades, there have been increasing discussions around which terms should be used to talk about autism. Whilst these discussions have largely revolved around the suitability of identity‐first language and person‐first language, more recently this debate has broadened to encompass other autism‐related terminology (e.g., ‘high‐functioning’). To date, academic studies have not investigated the language preferences of autistic individuals outside of the United Kingdom or Australia, nor have they compared levels of endorsement across countries. Hence, the current study adopted a mixed‐methods approach, employing both quantitative and qualitative techniques, to explore the linguistic preferences of 654 English‐speaking autistic adults across the globe. Despite variation in levels of endorsement between countries, we found that the most popular terms were similar—the terms ‘Autism’, ‘Autistic person’, ‘Is autistic’, ‘Neurological/Brain Difference’, ‘Differences’, ‘Challenges’, ‘Difficulties’, ‘Neurotypical people’, and ‘Neurotypicals’ were consistently favored across countries. Despite relative consensus across groups, both our quantitative and qualitative data demonstrate that there is no universally accepted way to talk about autism. Our thematic analysis revealed the reasons underlying participants’ preferences, generating six core themes, and illuminated an important guiding principle—to respect personal preferences. These findings have significant implications for informing practice, research and language policy worldwide.

Exclusion of females in autism research: Empirical evidence for a “leaky” recruitment‐to‐research pipeline

Abstract: Autism spectrum disorder (ASD) is characterized by challenges in social communication and the presence of repetitive behaviors or restricted interests. Notably, males are four times as likely as females to be diagnosed with autism. Despite efforts to increase representation and characterization of autistic females, research studies consistently enroll small samples of females, or exclude females altogether. Importantly, researchers often rely on standardized measures to confirm diagnosis prior to enrollment in research studies. We retrospectively analyzed the effects of one such measure (Autism Diagnostic Observation Schedule, ADOS) on research inclusion/exclusion rates by sex in autistic adults, all of whom had a preexisting community diagnosis of autism (n = 145, 95 male, 50 female). Using the ADOS as a confirmatory diagnostic measure resulted in the exclusion of autistic females at a rate over 2.5 times higher than that of autistic males. We compared sex ratios in our sample to those in other large, publically available datasets that rely either on community diagnosis (6 datasets, total n = 42,209) or standardized assessments (2 datasets, total n = 214) to determine eligibility of participants for research. Reliance on community diagnosis rather than confirmatory diagnostic assessments resulted in significantly more equal sex ratios. These results provide evidence for a “leaky” recruitment‐to‐research pipeline for females in autism research.

A conceptual model of risk and protective factors for autistic burnout

Abstract: Early qualitative research indicates that autistic burnout is commonly experienced by autistic people and is associated with significant, negative consequences for their mental health, wellbeing, and quality of life, including suicidality. Findings to date suggest that factors associated with being autistic and the widespread lack of autism awareness and acceptance within society contribute to the onset and recurrence of autistic burnout. Based on autistic adults' descriptions of their lived experiences, a Conceptual Model of Autistic Burnout (CMAB) is proposed, which describes a series of hypothesized relationships between identified risk and protective factors that may contribute to, or buffer against, autistic burnout. The theoretical framework for the CMAB is based on the Social‐Relational model of disability and neurodiversity paradigm, and the Job Demands‐Resources model of burnout, and Conservation of Resources theory. The CMAB offers a holistic perspective for understanding individual, social, and environmental factors that can influence autistic burnout via various direct and indirect pathways. Autistic burnout research is in its infancy and the CMAB provides a foundation for future investigations about this condition.

A further study of relations between motor impairment and social communication, cognitive, language, functional impairments, and repetitive behavior severity in children with ASD using the SPARK study dataset

Abstract: Motor impairments are pervasive and persistent in children with autism spectrum disorder (ASD) throughout childhood and adolescence. Based on recent studies examining motor impairments in children with ASD between 5 and 15 years (i.e., SPARK study sample), 87–88% of this population is at‐risk for a motor impairment, these problems persisted until 15 years, and related to their core (social communication skills and repetitive behaviors [RBs]) and comorbid (language, cognitive, and functional) impairments. Persistent motor impairments extending into adolescence/adulthood could negatively impact their independent daily living skills, physical fitness/activity levels, and physical/mental health. While multiple studies have examined relations between motor dimensions and core/comorbid impairments in young children with ASD, few studies have examined such relations in school‐age children/adolescents with ASD. This paper conducts a further multidimensional study of which motor domains (i.e., gross‐motor including visuo‐motor or multilimb coordination/planning, fine motor [FM] or general coordination [GC] skills) best distinguish subgroups of school‐age children/adolescents with ASD and help predict core and comorbid impairments after accounting for age and sex. Visuomotor, FM and certain GC skills were better at explaining variations in/predicting social communication impairments whereas FM skills were slightly better at explaining variations in/predicting RB severity. Multilimb coordination/planning and FM skills explained variations in/predicted cognitive delays whereas visuomotor and FM skills explained variations in and better predicted language delays. All three motor dimensions explained variations in/predicted functional delays. This study provides further evidence for inclusion of motor impairments within the ASD definition (criteria or specifiers).

Sensory features in autism: Findings from a large population‐based surveillance system

Abstract: Sensory features (i.e., atypical responses to sensory stimuli) are included in the current diagnostic criteria for autism spectrum disorder. Yet, large population‐based studies have not examined these features. This study aimed to determine the prevalence of sensory features among autistic children, and examine associations between sensory features, demographics, and co‐occurring problems in other areas. Analysis for this study included a sample comprised of 25,627 four‐ or eight‐year‐old autistic children identified through the multistate Autism and Developmental Disabilities Monitoring Network (2006–2014). We calculated the prevalence of sensory features and applied multilevel logistic regression modeling. The majority (74%; 95% confidence interval: 73.5%–74.5%) of the children studied had documented sensory features. In a multivariable model, children who were male and those whose mothers had more years of education had higher odds of documented sensory features. Children from several racial and ethnic minority groups had lower odds of documented sensory features than White, non‐Hispanic children. Cognitive problems were not significantly related to sensory features. Problems related to adaptive behavior, emotional states, aggression, attention, fear, motor development, eating, and sleeping were associated with higher odds of having documented sensory features. Results from a large, population‐based sample indicate a high prevalence of sensory features in autistic children, as well as relationships between sensory features and co‐occurring problems. This study also pointed to potential disparities in the identification of sensory features, which should be examined in future research. Disparities should also be considered clinically to avoid reduced access to supports for sensory features and related functional problems.

Representativeness of autistic samples in studies recruiting through social media

Abstract: Survey‐based research with recruitment through online channels is a convenient way to obtain large samples and has recently been increasingly used in autism research. However, sampling from online channels may be associated with a high risk of sampling bias causing findings not to be generalizable to the autism population. Here we examined autism studies that have sampled on social media for markers of sampling bias. Most samples showed one or more indicators of sampling bias, in the form of reversed sex ratio, higher employment rates, higher education level, lower fraction of individuals with intellectual disability, and later age of diagnosis than would be expected when comparing with for example population study results from published research. Findings from many of the included studies are therefore difficult to generalize to the broader autism population. Suggestions for how research strategies may be adapted to address some of the problems are discussed.

Motor performance, praxis, and social skills in autism spectrum disorder and developmental coordination disorder

Abstract: Previous research has shown that individuals with autism spectrum disorder (ASD) and developmental coordination disorder (DCD) may have overlapping social and motor skill impairments. This study compares ASD, DCD, and typically developing (TD) youth on a range of social, praxis and motor skills, and investigates the relationship between these skills in each group. Data were collected on participants aged 8–17 (n = 33 ASD, n = 28 DCD, n = 35 TD). Overall, the clinical groups showed some similar patterns of social and motor impairments but diverged in praxis impairments, cognitive empathy, and Theory of Mind ability. When controlling for both social and motor performance impairments, the ASD group showed significantly lower accuracy on imitation of meaningful gestures and gesture to command, indicating a prominent deficit in these praxis skills in ASD.

Identifying autism symptom severity trajectories across childhood

Abstract: An individual's autism symptom severity level can change across childhood. The prevalence and direction of change, however, are still not well understood. Nor are the characteristics of children that experience change. Symptom severity trajectories were evaluated from early to middle childhood (approximately ages 3–11) for 182 autistic children. Symptom severity change was evaluated using individual change scores and the Reliable Change Index. Fifty‐one percent of participants experienced symptom severity change: 27% of children decreased in severity, 24% increased and 49% were stable. Symptom severity decreases were more common during early childhood. Severity increases occurred at both early and middle childhood but increase in social affect severity was especially prominent during middle childhood. Most children experienced significant change during only one period and remained stable during the other. Girls decreased more and increased less in symptom severity than boys. Children that increased in severity decreased in adaptive functioning across childhood. Exploratory analyses indicated that a decrease in severity was associated with higher parental education level and older parental age at the time of the child's birth. Conversely, increase in autism severity was associated with lower parental education level and younger parental age at the child's birth. These findings extend recent observations that symptom severity change is more likely than previously appreciated. An understanding of the role of both biological and sociodemographic factors in determining a child's symptom trajectory may factor into future decisions on allocation and type of interventions distributed to young autistic children.

Associations between co‐occurring conditions and age of autism diagnosis: Implications for mental health training and adult autism research

Abstract: Adult autism studies are increasingly comprised of later‐diagnosed adults, yet little is known about how these adults compare to those diagnosed earlier in life. The present study examines medical and psychiatric conditions endorsed by autistic adults and documents differences between those diagnosed with ASD in childhood versus adulthood, as well as across age groups and sex at birth. 4657 legally independent adults (ages 18–85, M = 33.4 years) with professional ASD diagnoses who completed a medical questionnaire were drawn from the Simons Powering Autism Research Knowledge (SPARK) study. Chi square analyses, t‐tests, and logistic regressions were used to compare medical and psychiatric conditions between age groups, sex at birth and adults diagnosed in childhood (before age 21) versus adulthood (at or after 21 years). Overall number of conditions endorsed as being diagnosed by a professional was high, with an average of 1.69 (SD = 2.01) medical or developmental and 2.98 (SD = 2.29) psychiatric conditions reported across the sample. Females were more likely to endorse psychiatric conditions (OR = 1.68). Adult‐diagnosed adults were more likely to endorse psychiatric conditions (OR = 2.71) and reported more lifetime psychiatric diagnoses (M = 3.15, SD = 2.23) than their childhood‐diagnosed counterparts (M = 2.81, SD = 2.33). These findings underscore the need for research to better understand and treat co‐occurring psychiatric conditions in autistic adults and report and consider the age of diagnosis in adult autism samples. Moreover, results suggest it is imperative that mental health professionals receive autism training to promote accurate differential diagnosis and equitable access to mental health care for autistic adults with co‐occurring psychiatric conditions.

Motor skills predict adaptive behavior in autistic children and adolescents

Abstract: It is well-documented that intelligence quotient (IQ) is a poor predictor of adaptive behavior scores in autism, with autistic children having lower adaptive behavior scores than would be predicted based on their IQ scores. Differences in motor skills may explain the variability in their adaptive behavior scores. The current study examined how motor skills might explain autistic individuals' low adaptive behavior scores and which individual components of IQ (i.e., verbal comprehension and perceptual reasoning) and motor skills (i.e., manual dexterity, aiming and catching, and balance) may drive this effect. We examined the associations between IQ, motor skills, calibrated severity, and adaptive behavior scores in 45 autistic children and adolescents. Using a t-test, we found a significant difference (p <0.001) between full-scale IQ and adaptive behavior scores, indicating that our participants' adaptive behavior scores were lower than would be expected given their full-scale IQ. Using a linear regression, we investigated whether motor skills predicted adaptive behavior in autistic children and adolescents and found that motor skills scores were associated with adaptive behavior scores (p = 0.022). To further investigate these associations, we used another linear regression to examine how individual components of IQ and motor skills predicted adaptive behavior scores in autistic children and adolescents. Our results indicated that manual dexterity scores were associated with adaptive behavior scores (p = 0.036). These findings clearly illustrate the need for further understanding of autistic individuals' difficulties with adaptive behavior and the potential role of motor skill difficulties that may underlie these difficulties. LAY SUMMARY: Autistic children have lower adaptive behavior scores (e.g., daily living skills, social skills, communication) than intelligence scores (e.g., verbal and perceptual skills) along with difficulties with motor skills. Motor skills may explain the gap between adaptive behavior and intelligence. We found motor skills were associated with adaptive behavior in autistic children and adolescents. In particular, hand coordination was associated with adaptive behavior. We need to better understand how autistic individuals' motor skills impact their adaptive behavior to provide effective supports.

Current and lifetime somatic symptom burden among transition‐aged autistic young adults

Abstract: Somatic symptoms are the most common cause of outpatient medical visits in the general population, yet their presence and severity in individuals on the autism spectrum has rarely been studied. We sought to assess the prevalence, impact, and clinical correlates of 14 commonly reported somatic symptoms in a sample of 290 transition‐aged autistic young adults (mean [SD] age: 23.10 [2.38] years, range 18–26; 76.7% diagnosed with autism before age 18) recruited from the Simons Foundation SPARK participant pool. A modified version of the Patient Health Questionnaire–15 was used to assess somatic symptom prevalence/impact, along with measures of depression, anxiety, autistic traits, and quality of life. Somatic symptom burden was much higher in autistic young adults than previously reported in the general population. The most commonly reported current symptoms were fatigue (72.8%), sleep problems (69.0%), and menstrual problems (61.4% of females). Moderate or severe symptom levels were reported by 53.9% of females and 18.75% of males in our cohort, with the odds of females endorsing any given symptom being 2–4 times greater than males. Both individual symptoms and total symptom burden were related to higher levels of depression, anxiety, and autistic traits, along with lower quality of life. Despite little research on this topic previously, somatic symptoms are highly prevalent in autistic young adults, particularly women. Future research is needed to investigate links between somatic symptoms, medical and psychiatric morbidity, and health care utilization in the autistic population.

Reexamining empathy in autism: Empathic disequilibrium as a novel predictor of autism diagnosis and autistic traits

Abstract: A large body of research showed that autistic people have intact emotional (affective) empathy alongside reduced cognitive empathy. However, there are mixed findings and these call for a more subtle understanding of empathy in autism. Empathic disequilibrium refers to the imbalance between emotional and cognitive empathy and is associated with a higher number of autistic traits in the typical population. Here we examined whether empathic disequilibrium predicts both the number of autistic traits and autism diagnosis. In a large sample of autistic (N = 1905) and typical individuals (N = 3009), we examined empathic disequilibrium and empathy as predictors of autistic traits and autism diagnosis, using a polynomial regression with response surface analysis. Empathy and autistic traits were measured using validated self‐report questionnaires. Both empathic disequilibrium and empathy predicted linearly and non‐linearly autism diagnosis and autistic traits. Specifically, a tendency towards higher emotional than cognitive empathy (empathic disequilibrium towards emotional empathy) predicted both autism diagnosis and the social domain of autistic traits, while higher cognitive than emotional empathy was associated with the non‐social domain of autism. Empathic disequilibrium was also more prominent in autistic females. This study provides evidence that beyond empathy as was measured thus far, empathic disequilibrium offers a novel analytical approach for examining the role of empathy. Empathic disequilibrium allows for a more nuanced understanding of the links between empathy and autism.

Diagnosing autism in low‐income countries: Clinical record‐based analysis in Sri Lanka

Abstract: Use of autism diagnosing standards in low‐income countries (LICs) are restricted due to the high price and unavailability of trained health professionals. Furthermore, these standards are heavily skewed towards developed countries and LICs are underrepresented. Due to such constraints, many LICs use their own ways of assessing autism. This is the first retrospective study to analyze such local practices in Sri Lanka. The study was conducted at Ward 19B of Lady Ridgeway Hospital (LRH) using the clinical forms filled for diagnosing ASD. In this study, 356 records were analyzed, from which 79.5% were boys and the median age was 33 months. For each child, the clinical form together with the Childhood Autism Rating Scale (CARS) value were recorded. In this study, a Clinically Derived Autism Score (CDAS) is obtained from the clinical forms. Scatter plot and Pearson product moment correlation coefficient were used to benchmark CDAS with CARS, and it was found CDAS to be positively and moderately correlated with CARS. In identifying the significant variables, a logistic regression model was built based on clinically observed data and it evidenced that “Eye Contact,” “Interaction with Others,” “Pointing,” “Flapping of Hands,” “Request for Needs,” “Rotate Wheels,” and “Line up Things” variables as the most significant variables in diagnosing autism. Based on these significant predictors, the classification tree was built. The pruned tree depicts a set of rules, which could be used in similar clinical environments to screen for autism.

A full semantic toolbox is essential for autism research and practice to thrive

Abstract: Individuals diagnosed with autism spectrum disorder (ASD) present with a highly diverse set of challenges, disabilities, impairments and strengths. Recently, it has been suggested that researchers and practitioners avoid using certain words to describe the difficulties and impairments experienced by individuals with ASD to reduce stigma. The proposed limitations on terminology were developed by only a subset of the autism community, and the recommendations are already causing negative consequences that may be harmful to future scientific and clinical endeavors and, ultimately, to people with ASD. No one should have the power to censor language to exclude the observable realities of autism. Scientists and clinicians must be able to use any scientifically accurate terms necessary to describe the wide range of autistic people they study and support, without fear of censure or retribution.

Heritability of social behavioral phenotypes and preliminary associations with autism spectrum disorder risk genes in rhesus macaques: A whole exome sequencing study

Abstract: Nonhuman primates and especially rhesus macaques (Macaca mulatta) have been indispensable animal models for studies of various aspects of neurobiology, developmental psychology, and other aspects of neuroscience. While remarkable progress has been made in our understanding of influences on atypical human social behavior, such as that observed in autism spectrum disorders (ASD), many significant questions remain. Improved understanding of the relationships among variation in specific genes and variation in expressed social behavior in a nonhuman primate would benefit efforts to investigate risk factors, developmental mechanisms, and potential therapies for behavioral disorders including ASD. To study genetic influences on key aspects of social behavior and interactions—individual competence and/or motivation for specific aspects of social behavior—we quantified individual variation in social interactions among juvenile rhesus macaques using both a standard macaque ethogram and a macaque‐relevant modification of the human Social Responsiveness Scale. Our analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with estimated quantitative genetic effects similar to that described for ASD in human children. We also performed exome sequencing and analyzed variants in 143 genes previously suggested to influence risk for human ASD. We find preliminary evidence for genetic association between specific variants and both individual behaviors and multi‐behavioral factor scores. To our knowledge, this is the first demonstration that spontaneous social behaviors performed by free‐ranging juvenile rhesus macaques display significant genetic heritability and then to use exome sequencing data to examine potential macaque genetic associations in genes associated with human ASD.

Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts

Abstract: Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD‐related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking‐related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort‐specific ORs were meta‐analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72–1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02–2.03). Children of smoking (versus non‐smoking) mothers had more ASD traits (SRS T‐score + 2.37 points, 95% CI, 0.73–4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non‐preterm children. Limitations resulting from self‐reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners.

Increased prefrontal GABA concentrations in adults with autism spectrum disorders

Abstract: The excitatory‐inhibitory imbalance hypothesis postulates dysregulation of the gamma‐aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate‐glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon.

Effects of age on the hippocampus and verbal memory in adults with autism spectrum disorder: Longitudinal versus cross‐sectional findings

Abstract: Research studying aging in adults with autism spectrum disorder (ASD) is growing, but longitudinal work is needed. Autistic adults have increased risk of dementia, altered hippocampal volumes and fornix integrity, and verbal memory difficulties compared with neurotypical (NT) adults. This study examined longitudinal aging in middle‐age adults with ASD versus a matched NT group, and compared findings with cross‐sectional age effects across a broad adult age range. Participants were 194 adults with (n = 106; 74 male) and without (n = 88; 52 male) ASD, ages 18–71. Participants (n = 45; 40–70 age range) with two visits (2–3 years apart) were included in a longitudinal analysis. Hippocampal volume, fornix fractional anisotropy (FA), and verbal memory were measured via T1‐weighted MRI, diffusion tensor imaging, and the Rey Auditory Verbal Learning Test, respectively. Longitudinal mixed models were used for hippocampal system variables and reliable change index categories were used for Auditory Verbal Learning Test analyses. Multivariate regression was used for cross‐sectional analyses. Middle‐age adults with ASD had greater longitudinal hippocampal volume loss and were more likely to show clinically meaningful decline in short‐term memory, compared with NT. In contrast, cross‐sectional associations between increasing age and worsening short‐term memory were identified in NT, but not autistic adults. Reduced fornix FA and long‐term memory in ASD were found across the broad cross‐sectional age range. These preliminary longitudinal findings suggest accelerated hippocampal volume loss in ASD and slightly higher rates of clinically‐meaningful decline in verbal short‐term memory. Contradictory cross‐sectional and longitudinal results underscore the importance of longitudinal aging research in autistic adults.

Altered medial prefrontal cortex and dorsal raphé activity predict genotype and correlate with abnormal learning behavior in a mouse model of autism‐associated 2p16.3 deletion

Abstract: 2p16.3 deletion, involving NEUREXIN1 (NRXN1) heterozygous deletion, substantially increases the risk of developing autism and other neurodevelopmental disorders. We have a poor understanding of how NRXN1 heterozygosity impacts on brain function and cognition to increase the risk of developing the disorder. Here we characterize the impact of Nrxn1α heterozygosity on cerebral metabolism, in mice, using 14C‐2‐deoxyglucose imaging. We also assess performance in an olfactory‐based discrimination and reversal learning (OB‐DaRL) task and locomotor activity. We use decision tree classifiers to test the predictive relationship between cerebral metabolism and Nrxn1α genotype. Our data show that Nrxn1α heterozygosity induces prefrontal cortex (medial prelimbic cortex, mPrL) hypometabolism and a contrasting dorsal raphé nucleus (DRN) hypermetabolism. Metabolism in these regions allows for the predictive classification of Nrxn1α genotype. Consistent with reduced mPrL glucose utilization, prefrontal cortex insulin receptor signaling is decreased in Nrxn1α+/− mice. Behaviorally, Nrxn1α+/− mice show enhanced learning of a novel discrimination, impaired reversal learning and an increased latency to make correct choices. In addition, male Nrxn1α+/− mice show hyperlocomotor activity. Correlative analysis suggests that mPrL hypometabolism contributes to the enhanced novel odor discrimination seen in Nrxn1α+/− mice, while DRN hypermetabolism contributes to their increased latency in making correct choices. The data show that Nrxn1α heterozygosity impacts on prefrontal cortex and serotonin system function, which contribute to the cognitive alterations seen in these animals. The data suggest that Nrxn1α+/− mice provide a translational model for the cognitive and behavioral alterations seen in autism and other neurodevelopmental disorders associated with 2p16.3 deletion.

Insufficient evidence for inclusion of motor deficits in the ASD diagnostic criteria: A response to Bhat (2021)

Abstract: In a study of children with autism spectrum disorder (ASD) from the Simons Powering Autism Research (SPARK) registry (n = 13,887), Dr. Anjana Bhat reported that the majority of participants were at risk for motor impairments based on their scores on the Developmental Coordination Disorder-Questionnaire (DCD-Q) (Bhat, 2021). Results also indicated relationships between DCD-Q scores and other ASD-associated impairments (i.e., severity of social communication; repetitive behavior; cognitive, language, and functional impairments). Dr. Bhat concluded that these findings highlight, “the need to recognize motor impairments as one of the diagnostic criteria or specifiers for ASD, and the need for appropriate motor screening and assessment of children with ASD” (Bhat, 2021, p. 202). She recently reiterated this claim in a follow-up publication using the same sample (Bhat et al., 2022). While we agree with the recommendation regarding screening and assessment of motor problems in children with ASD (as well as all children), we do not agree that there is enough evidence to support inclusion of motor impairments within the ASD definition. Specifically, relationships between scores on the DCD-Q and other measures of ASD-associated impairments do not necessarily indicate a primary connection between motor problems and ASD. In fact, poor performance alone on the DCD-Q could merely be a reflection of disinterest in the tasks, and/or a biproduct of reduced opportunities to participate in certain motor-based activities (many of which are social in nature). Validating this measure in ASD to ensure that it is measuring what it is intended to measure is necessary before using it to draw conclusions about rates of motor impairment in ASD. Therefore, claims that these findings from the DCD-Q support the need to recognize motor impairments as a diagnostic criterion or specifier for ASD are overstated. It is widely known that individuals with ASD experience a myriad of challenges that are not explicitly included within the two core symptom domains of social communication deficits and restricted and repetitive behaviors. In addition to motor impairments, a variety of developmental (e.g., language), behavioral (e.g., feeding and sleeping problems), psychiatric, neurological, sensory-based (e.g., ophthalmological and audiological), and other medical problems (e.g., gastrointestinal) are commonly observed in ASD. Why, then, would we recommend including motor impairments as a core ASD symptom and not these others? Interestingly, impairment in another developmental domain, language, had previously been included in DSMIV criteria for Autistic Disorder but was not included in the DSM-5 because it is neither specific nor universal to ASD (Rosen et al., 2021). This same argument holds for keeping motor problems from being included in the current diagnostic criteria. Further, challenges associated with measurement of motor impairment in individuals with ASD (using instruments such as the DCD-Q) raise questions about whether motor impairment should be considered as a separate ASD specifier. It is important to acknowledge that the existing ASD specifier, “associated with another neurodevelopmental, mental, or behavioral disorder” (American Psychiatric Association, 2013, p. 51), could include developmental coordination disorder (DCD). However, we urge caution in diagnosing DCD in the context of ASD, given the complexities of assessing true motor impairment in this population. This is particularly the case for individuals with ASD with co-occurring intellectual disability (ID). DCD (like ASD) should only be diagnosed when it is not better explained by ID, as the text on ID states, “delayed motor language and social milestones may be identifiable within the first 2 years of life among those with more severe intellectual disability” (American Psychiatric Association, 2013, p. 38). Thus, for a disorder in which motor delays are among the first signs of the condition, it is likely that impaired motor development will frequently be better explained by ID. The need to establish that motor deficits are beyond what can be attributed to ID clearly raises concern about diagnosing DCD when ASD + ID is present. But what about ASD without ID? The text for DCD states, “Individuals with autism spectrum disorder may be uninterested in participating in tasks requiring complex coordination skills, such as ball sports, which will affect test performance and function but not reflect core motor competence” (American Psychiatric Association, 2013, p. 77). Thus, while it may be common for individuals with ASD, with or without ID, to exhibit impaired performance in motor activities that align with a DCD diagnosis, we must carefully consider how performance is affected by variables such as motivation, practice, and opportunity to participate in these activities. Further, to make a co-occurring Received: 22 May 2022 Accepted: 19 June 2022

Alteration of the fecal microbiota in Chinese children with autism spectrum disorder

Abstract: Autism spectrum disorder (ASD) is associated with altered gut microbiota. However, there has been little consensus on the altered bacterial species and studies have had small sample sizes. We aimed to identify the taxonomic composition and evaluate the changes in the fecal microbiota in Chinese children with ASD by using a relatively large sample size. We conducted a case–control study of 101 children with ASD and 103 healthy controls in China. Demographic information and fecal samples were collected, and the V3‐V4 hypervariable regions of the bacterial 16S ribosomal RNA (rRNA) gene were sequenced. The alpha and beta diversities between the two groups were significantly different. After correcting for multiple comparisons, at the phylum level the relative abundances of Actinobacteria and Proteobacteria in the case group were significantly higher than those in the control group. The relative abundance of the Escherichia‐Shigella genus in the case group was significantly higher than that of the control group, and the relative abundance of Blautia and unclassified_f__Lachnospiraceae in the control group were higher than that of the case group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that children with ASD may have disturbed functional pathways, such as amino acid metabolism, cofactor and vitamin metabolism, and the AMP‐activated protein kinase signaling pathway. This study revealed the characteristics of the intestinal flora of Chinese children with ASD and provided further evidence of gut microbial dysbiosis in ASD.

Differential effects of COVID‐related lockdown on sleep–wake rhythms in adults with autism spectrum disorder compared to the general population

Abstract: COVID‐related lockdown led to a radical modification of daily activities and routines which are known to affect sleep. Compared to the general population, participants with autism may be particularly vulnerable to the repercussions of lockdown on sleep, given their intrinsic inflexible adherence to routines and the high overall prevalence of sleep disturbances in this population. The study is a French nation‐wide online survey assessing sleep–wake rhythms and behaviors known to affect sleep (daily screen time, daylight exposure, and physical activity), before and during COVID‐related lockdown. Respondents were 207 adults with autism (56% female) and 1652 adults of the general population (77% female), with a mean age 35.3 years (SD 11.3). Before lockdown, the adults with autism displayed on average later bedtime and waking hours, lower sleep quality, more evening screen time, less exposure to daylight, and less exercise (all p < 0.01). Lockdown affected all studied measures of sleep and related exposures in a similar way in both groups: poorer self‐rated sleep quality as well as a less regular and delayed sleep–wake rhythm, longer screen time in the evening and less exposure to daylight (all p < 0.001). Adults with autism displayed significantly higher levels of sleep and circadian rhythm disturbances and less favorable daily routines known to regulate sleep. While the effect of confinement on sleep and sleep related behaviors was similar in both groups, the results highlight that the pre‐existing shift in circadian rhythms and lifestyles in adults with ASD further deteriorated during lockdown.

Associations between sleep problems and domains relevant to daytime functioning and clinical symptomatology in autism: A meta‐analysis

Abstract: Autistic individuals experience significantly higher rates of sleep problems compared to the general population, which negatively impacts various aspects of daytime functioning. The strength of associations across domains of functioning has not yet been summarized across studies. The present meta‐analysis examined the strength of associations between sleep problems and various domains of daytime functioning in autistic individuals. Searches were conducted in EMBASE, PubMed, Web of Science, and Google Scholar through May 2020. Inclusion criteria were: an index of sleep disturbance in individuals diagnosed with autism spectrum disorder (ASD); data collected prior to any sleep‐related intervention; statistical data indicating relations between sleep problems and outcomes relevant to behavior, cognition, and physical or mental health. Exclusion criteria were: statistics characterizing the relationship between sleep disturbance and outcome variables that partialled out covariates; studies examining correlations between different measures of sleep disturbance. Participants totaled 15,074 from 49 published articles and 51 samples, yielding 209 effect sizes. Sleep problems were significantly associated with more clinical symptomatology and worse daytime functioning. Subgroup analyses demonstrated that sleep problems were most strongly associated with internalizing and externalizing symptoms and executive functioning, followed by core autism symptoms, family factors, and adaptive functioning. Findings highlight the far‐reaching consequences of sleep problems on daytime functioning for autistic individuals and support the continued prioritization of sleep as a target for intervention through integrated care models to improve wellbeing.

Applying a public health approach to autism research: A framework for action

Abstract: Most published autism research, and the funding that supports it, remains focused on basic and clinical science. However, the public health impact of autism drives a compelling argument for utilizing a public health approach to autism research. Fundamental to the public health perspective is a focus on health determinants to improve quality of life and to reduce the potential for adverse outcomes across the general population, including in vulnerable subgroups. While the public health research process can be conceptualized as a linear, 3‐stage path consisting of discovery – testing – translation/dissemination/implementation, in this paper we propose an integrated, cyclical research framework to advance autism public health objectives in a more comprehensive manner. This involves discovery of primary, secondary and tertiary determinants of health in autism; and use of this evidence base to develop and test detection, intervention, and dissemination strategies and the means to implement them in ‘real world’ settings. The proposed framework serves to facilitate identification of knowledge gaps, translational barriers, and shortfalls in implementation; guides an iterative research cycle; facilitates purposeful integration of stakeholders and interdisciplinary researchers; and may yield more efficient achievement of improved health and well‐being among persons on the autism spectrum at the population‐level.

The impact of prefrontal transcranial direct current stimulation (tDCS) on theory of mind, emotion regulation and emotional‐behavioral functions in children with autism disorder: A randomized, sham‐controlled, and parallel‐group study

Abstract: Advances in our knowledge about the neuropsychological mechanisms underlying core deficits in autism spectrum disorder (ASD) have produced several novel treatment modalities. One of these approaches is modulation of activity of the brain regions involved in ASD symptoms. This study examined the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) on autism symptom severity, theory of mind, emotion regulation strategies, and emotional‐behavioral functions in children with ASD. Thirty‐two children (Mage = 10.16, SD = 1.93, range 7–12 years) diagnosed with ASD were randomly assigned to active (N = 17) or sham stimulation (N = 15) groups in a randomized, sham‐controlled, parallel‐group design. Participants underwent 10 sessions of active (1.5 mA, 15 min, bilateral left anodal/right cathodal DLPFC, 2 sessions per week) or sham tDCS. Autism symptom severity, theory of mind, emotion regulation strategies, and emotional‐behavioral functioning of the patients were assessed at baseline, immediately after the intervention, and 1 month after the intervention. A significant improvement of autism symptom severity (i.e., communication), theory of mind (i.e., ToM 3), and emotion regulation strategies was observed for the active as compared to the sham stimulation group at the end of the intervention, and these effects were maintained at the one‐month follow‐up. The results suggest that repeated tDCS with anodal stimulation of left and cathodal stimulation of right DLPFC improves autism symptom severity as well as social cognition and emotion regulation in ASD.

Is traditional back translation enough? Comparison of translation methodology for an ASD screening tool

Abstract: Early identification of autism spectrum disorders (ASD) in non‐English speaking children often relies on translation of English ASD screening measures. Most measures employ a forward‐back translation approach, despite data suggesting that this method may result in poor psychometric properties. Some studies in non‐ASD fields have suggested that a rigorous method of translation with cultural adaptation may yield better psychometric properties, but no studies in the ASD field have compared the two approaches directly. This investigation compares these two translation methodologies to determine if they produce psychometrically similar or dissimilar measures. Three hundred and eighty US‐based Spanish‐speaking caregivers of children 8–16 months old were randomly assigned to complete either a forward‐back Spanish translation or a rigorous translation with cultural adaptation of a parent‐report ASD screening tool. Measurement invariance analyses determined that the two translations were psychometrically dissimilar. Additional qualitative explanatory methods using cognitive interviews examined textual differences and participant preferences between non‐invariant items.

Increased perceived stress is negatively associated with activities of daily living and subjective quality of life in younger, middle, and older autistic adults

Abstract: 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.

Patterns of sensory modulation by age and sex in young people on the autism spectrum

Abstract: Sensory modulation symptoms form a diagnostic criterion for autism spectrum disorder and are associated with significant daily functional limitations. Utilizing caregiver report on Short Sensory Profile‐2 (SSP‐2) for 919 autistic children (3–14.11 years), we examined the expression of sensory modulation symptoms by age and sex and investigated the existence of specific sensory modulation subtypes. Sensory modulation symptoms appeared to peak in frequency during middle childhood, particularly in sensory sensitivity and avoidance. Symptoms associated with sensory hypo‐reactivity and seeking tended not differ between age cohorts. Males and females demonstrated similar overall sensory modulation profiles, however, females showed elevated symptoms relating to sensory sensitivity. Model‐based cluster analysis revealed five interpretable sensory modulation subtypes which related to symptom severity (low, mid‐range, high). Subtypes demonstrating mid‐range symptom severity differed in focus on sensory hyper‐reactivity or seeking symptoms. The findings of this study report for the first time that age‐related differences in sensory modulation symptoms may be associated with sensory hyper‐reactivity only. The subtyping results also suggest that sensory modulation symptom severity is a reliable means of classifying variance within autistic children, however, consideration of differences in the behavioral strategies employed by individuals to manage sensory modulation symptoms may inform tailored supportive strategies.

LRFN5 locus structure is associated with autism and influenced by the sex of the individual and locus conversions

Abstract: LRFN5 is a regulator of synaptic development and the only gene in a 5.4 Mb mammalian‐specific conserved topologically associating domain (TAD); the LRFN5 locus. An association between locus structural changes and developmental delay (DD) and/or autism was suggested by several cases in DECIPHER and own records. More significantly, we found that maternal inheritance of a specific LRFN5 locus haplotype segregated with an identical type of autism in distantly related males. This autism‐susceptibility haplotype had a specific TAD pattern. We also found a male/female quantitative difference in the amount histone‐3‐lysine‐9‐associated chromatin around the LRFN5 gene itself (p < 0.01), possibly related to the male‐restricted autism susceptibility. To better understand locus behavior, the prevalence of a 60 kb deletion polymorphism was investigated. Surprisingly, in three cohorts of individuals with DD (n = 8757), the number of deletion heterozygotes was 20%–26% lower than expected from Hardy–Weinberg equilibrium. This suggests allelic interaction, also because the conversions from heterozygosity to wild‐type or deletion homozygosity were of equal magnitudes. Remarkably, in a control group of medical students (n = 1416), such conversions were three times more common (p = 0.00001), suggesting a regulatory role of this allelic interaction. Taken together, LRFN5 regulation appears unusually complex, and LRFN5 dysregulation could be an epigenetic cause of autism.