1. Adamson J, Brede J, Babb C, Serpell L, Jones CRG, Fox J, Mandy W. Towards identifying a method of screening for autism amongst women with restrictive eating disorders. Eur Eat Disord Rev;2022 (Jul 5)

OBJECTIVE: Up to 37% of patients with anorexia nervosa score above cut-off on autism screening measures. These individuals typically have poorer outcomes from standard eating disorder interventions and could therefore benefit from adaptations. Accurately identifying these individuals is important for improving autism referral processes and clinical pathway decisions. This study’s aim was to identify subscales of questionnaires measuring constructs associated with either autism or eating disorders that, when combined with traditional autism screening measures, would improve the ability to identify women with restrictive eating disorders who might benefit from a full autism assessment. METHOD: One hundred and sixty women with restrictive eating disorders, with (n = 42) or without (n = 118) an autism diagnosis completed a battery of questionnaires. Using conditional stepwise binary logistic regression, we attempted to improve the autism spectrum quotient 10 item’s (AQ-10) ability to discriminate between autistic and non-autistic women in a restrictive eating disorder sample. RESULTS: In a binary logistic regression model, the AQ-10 reliably discriminated between autistic and non-autistic women with an accuracy rate of 85% but had relatively low (69%) sensitivity, reflecting a high rate of false negatives. Adding three subscales to the model (Glasgow Sensory Questionnaire Auditory, Camouflaging Autistic Traits Questionnaire Compensation and Toronto Alexithymia Scale Externally Orientated Thinking) significantly improved its differentiating ability (accuracy = 88%, sensitivity = 76%, specificity = 92%). CONCLUSIONS: We have identified three subscales that, when used in combination with the AQ-10, may help clinicians understand the pattern of autistic traits in their patients with a restrictive eating disorder. This can inform clinical decisions about whether to refer for a full autism assessment and whether to adapt standard eating disorder treatments to accommodate autistic traits. Future studies are needed to test the model in samples where participants have undergone a full autism assessment.

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2. Alispahic S, Pellicano E, Cutler A, Antoniou M. Auditory perceptual learning in autistic adults. Autism Res;2022 (Jul 5)

The automatic retuning of phoneme categories to better adapt to the speech of a novel talker has been extensively documented across various (neurotypical) populations, including both adults and children. However, no studies have examined auditory perceptual learning effects in populations atypical in perceptual, social, and language processing for communication, such as populations with autism. Employing a classic lexically-guided perceptual learning paradigm, the present study investigated perceptual learning effects in Australian English autistic and non-autistic adults. The findings revealed that automatic attunement to existing phoneme categories was not activated in the autistic group in the same manner as for non-autistic control subjects. Specifically, autistic adults were able to both successfully discern lexical items and to categorize speech sounds; however, they did not show effects of perceptual retuning to talkers. These findings may have implications for the application of current sensory theories (e.g., Bayesian decision theory) to speech and language processing by autistic individuals. LAY SUMMARY: Lexically guided perceptual learning assists in the disambiguation of speech from a novel talker. The present study established that while Australian English autistic adult listeners were able to successfully discern lexical items and categorize speech sounds in their native language, perceptual flexibility in updating speaker-specific phonemic knowledge when exposed to a novel talker was not available. Implications for speech and language processing by autistic individuals as well as current sensory theories are discussed.

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3. Berry-Kravis E. Disease-Targeted Treatment Translation in Fragile X Syndrome as a Model for Neurodevelopmental Disorders. J Child Neurol;2022 (Jul 5):8830738221089740.

Fragile X syndrome (FXS), the most common monogenic cause of intellectual disability and autism spectrum disorder, has been one of the first neurodevelopmental disorders in which molecular and neuronal mechanisms of disease were identified, leading to the concept of targeting the underlying disease to reverse symptoms. Translating findings in basic science and animal models to humans with FXS has proven difficult. These challenges have prompted the FXS field to organize to build interlocking projects and initiatives to improve consistency of supportive care, make clinical research accessible to families, generate collaborative research on natural history, outcome measures and biomarkers, and create clinical trial consortia and novel trial designs. This work has resulted in improved success in recent clinical trials, providing key steps toward regulatory approval of disease-targeted treatments for FXS. Progress in the FXS field has informed translation of transformative new disease-targeted therapies for other monogenic neurodevelopmental disorders.

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4. Durkut M, Blok E, Suleri A, White T. The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study. Mol Autism;2022 (Jul 5);13(1):31.

OBJECTIVE: Autistic traits are associated with alterations in brain morphology. However, the anatomic location of these differences and their developmental trajectories are unclear. The primary objective of this longitudinal study was to explore the bidirectional relationship between autistic traits and brain morphology from childhood to adolescence. METHOD: Participants were drawn from a population-based cohort. Cross-sectional and longitudinal analyses included 1950 (mean age 13.5) and 304 participants (mean ages 6.2 and 13.5), respectively. Autistic traits were measured with the Social Responsiveness Scale. Global brain measures and surface-based measures of gyrification, cortical thickness and surface area were obtained from T(1)-weighted MRI scans. Cross-sectional associations were assessed using linear regression analyses. Cross-lagged panel models were used to determine the longitudinal bidirectional relationship between autistic traits and brain morphology. RESULTS: Cross-sectionally, higher levels of autistic traits in adolescents are associated with lower gyrification in the pars opercularis, insula and superior temporal cortex; smaller surface area in the middle temporal and postcentral cortex; larger cortical thickness in the superior frontal cortex; and smaller cerebellum cortex volume. Longitudinally, both autistic traits and brain measures were quite stable, with neither brain measures predicting changes in autistic traits, nor vice-versa. LIMITATIONS: Autistic traits were assessed at only two time points, and thus we could not distinguish within- versus between-person effects. Furthermore, two different MRI scanners were used between baseline and follow-up for imaging data acquisition. CONCLUSIONS: Our findings point to early changes in brain morphology in children with autistic symptoms that remain quite stable over time. The observed relationship did not change substantially after excluding children with high levels of autistic traits, bolstering the evidence for the extension of the neurobiology of autistic traits to the general population.

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5. Gosling CJ, Cartigny A, Mellier BC, Solanes A, Radua J, Delorme R. Efficacy of psychosocial interventions for Autism spectrum disorder: an umbrella review. Mol Psychiatry;2022 (Jul 5)

INTRODUCTION: The wide range of psychosocial interventions designed to assist people with Autism Spectrum Disorder (ASD) makes it challenging to compile and hierarchize the scientific evidence that supports the efficacy of these interventions. Thus, we performed an umbrella review of published meta-analyses of controlled clinical trials that investigated the efficacy of psychosocial interventions on both core and related ASD symptoms. METHODS: Each meta-analysis that was identified was re-estimated using a random-effects model with a restricted maximum likelihood estimator. The methodological quality of included meta-analyses was critically appraised and the credibility of the evidence was assessed algorithmically according to criteria adapted for the purpose of this study. RESULTS: We identified a total of 128 meta-analyses derived from 44 reports. More than half of the non-overlapping meta-analyses were nominally statistically significant and/or displayed a moderate-to-large pooled effect size that favored the psychosocial interventions. The assessment of the credibility of evidence pointed out that the efficacy of early intensive behavioral interventions, developmental interventions, naturalistic developmental behavioral interventions, and parent-mediated interventions was supported by suggestive evidence on at least one outcome in preschool children. Possible outcomes included social communication deficits, global cognitive abilities, and adaptive behaviors. Results also revealed highly suggestive indications that parent-mediated interventions improved disruptive behaviors in early school-aged children. The efficacy of social skills groups was supported by suggestive evidence for improving social communication deficits and overall ASD symptoms in school-aged children and adolescents. Only four meta-analyses had a statistically significant pooled effect size in a sensitivity analysis restricted to randomized controlled trials at low risk of detection bias. DISCUSSION: This umbrella review confirmed that several psychosocial interventions show promise for improving symptoms related to ASD at different stages of life. However, additional well-designed randomized controlled trials are still required to produce a clearer picture of the efficacy of these interventions. To facilitate the dissemination of scientific knowledge about psychosocial interventions for individuals with ASD, we built an open-access and interactive website that shares the information collected and the results generated during this umbrella review. PRE-REGISTRATION: PROSPERO ID CRD42020212630.

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6. Hsu TW, Bai YM, Tsai SJ, Chen TJ, Liang CS, Chen MH. Risk of parental major psychiatric disorders in patients with comorbid autism spectrum disorder and attention deficit hyperactivity disorder: A population-based family-link study. Aust N Z J Psychiatry;2022 (Jul 5):48674221108897.

OBJECTIVE: Few studies have investigated the parental risk of major psychiatric disorders among patients with comorbid autism spectrum disorder and attention deficit hyperactivity disorder. This study examined the differences in such risk among patients with autism spectrum disorder-only, with attention deficit hyperactivity disorder-only and both conditions. METHODS: Between 2001 and 2011, we enrolled 132,624 patients with autism spectrum disorder or attention deficit hyperactivity disorder and 1:10 matched controls for age, sex and demographics from the National Health Insurance Database of Taiwan. Poisson regression models were used to examine the risk of five major psychiatric disorders in the patients’ parents compared with those of the controls, including schizophrenia, bipolar disorder, major depressive disorder, alcohol use disorder, and substance use disorder. Patients were classified into the autism spectrum disorder-only, attention deficit hyperactivity disorder-only and dual-diagnosis groups. RESULTS: The parents of attention deficit hyperactivity disorder-only and dual-diagnosis groups had a higher likelihood to be diagnosed with (odds ratios [95% confidence intervals]) schizophrenia (attention deficit hyperactivity disorder: 1.48 [1.39, 1.57]; dual: 1.79 [1.45, 1.20]), bipolar disorder (attention deficit hyperactivity disorder: 1.91 [1.82, 2.01]; dual: 1.81 [1.51, 2.17]), major depressive disorder (attention deficit hyperactivity disorder: 1.94 [1.89, 2.00]; dual: 1.99 [1.81, 2.20]), alcohol use disorder (attention deficit hyperactivity disorder: 1.39 [1.33, 1.45]; dual: 1.20 [1.01, 1.42]) and substance use disorder (attention deficit hyperactivity disorder: 1.66 [1.59, 1.73]; dual: 1.34 [1.13, 1.58]) than the controls. In contrast, the parents of autism spectrum disorder-only group had a higher likelihood to be diagnosed with schizophrenia (1.77 [1.46, 2.15]) and major depressive disorder (1.45 [1.32, 1.61]) and a lower likelihood to be diagnosed with alcohol use disorder (0.68 [0.55, 0.84]) than the controls. CONCLUSION: The autism spectrum disorder-only group had a different parental incidence of major psychiatric disorders than the attention deficit hyperactivity disorder-only and dual-diagnosis groups. Our findings have implications for clinical practice and future genetic research.

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7. Li Q, Li Y, Liu B, Chen Q, Xing X, Xu G, Yang W. Prevalence of Autism Spectrum Disorder Among Children and Adolescents in the United States from 2019 to 2020. JAMA Pediatr;2022 (Jul 5)

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8. McQuaid GA, Weiss CH, Said AJ, Pelphrey KA, Lee NR, Wallace GL. Increased perceived stress is negatively associated with activities of daily living and subjective quality of life in younger, middle, and older autistic adults. Autism Res;2022 (Jul 5)

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.

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9. Rabeling A, Goolam M. Cerebral organoids as an in vitro model to study autism spectrum disorders. Gene Ther;2022 (Jul 5)

Autism spectrum disorders (ASDs) are a set of disorders characterised by social and communication deficits caused by numerous genetic lesions affecting brain development. Progress in ASD research has been hampered by the lack of appropriate models, as both 2D cell culture as well as animal models cannot fully recapitulate the developing human brain or the pathogenesis of ASD. Recently, cerebral organoids have been developed to provide a more accurate, 3D in vitro model of human brain development. Cerebral organoids have been shown to recapitulate the foetal brain gene expression profile, transcriptome, epigenome, as well as disease dynamics of both idiopathic and syndromic ASDs. They are thus an excellent tool to investigate development of foetal stage ASDs, as well as interventions that can reverse or rescue the altered phenotypes observed. In this review, we discuss the development of cerebral organoids, their recent applications in the study of both syndromic and idiopathic ASDs, their use as an ASD drug development platform, as well as limitations of their use in ASD research.

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10. Rodgers J, Goodwin J, Garland D, Grahame V, Isard L, Kernohan A, Labus M, Osborne MM, Parr JR, Rob P, Wright C, Freeston M. Coping with uncertainty in everyday situations (CUES©) to address intolerance of uncertainty in autistic children: an intervention feasibility trial. J Autism Dev Disord;2022 (Jul 5)

BACKGROUND: Anxiety related to uncertainty is common in autism. Coping with Uncertainty in Everyday Situations (CUES©) is a parent-mediated group intervention aiming to increase autistic children’s tolerance to uncertain situations. A pilot study was conducted to test its feasibility and acceptability. METHODS: Parents of 50 autistic children were randomised to receive CUES© or enhanced services as usual. RESULTS: All children met the clinical threshold for at least one anxiety disorder. Of the 26 participants randomised to CUES©, 72% attended 4-8 sessions. Parents and therapists reported they found CUES© useful and acceptable. CONCLUSIONS: Families were willing to be recruited and randomised, the format/content was feasible to deliver, and the outcome measures were acceptable. CUES© should be evaluated in a clinical and cost effectiveness randomised controlled trial.

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11. Villamor E, Susser ES, Cnattingius S. Defective placentation syndromes and autism spectrum disorder in the offspring: population-based cohort and sibling-controlled studies. Eur J Epidemiol;2022 (Jul 5)

Defective placentation underlies diverse syndromic manifestations that could affect brain development including: (1) placental abruption, (2) term preeclampsia with a small-for-gestational age (SGA) infant, (3) preterm preeclampsia, and (4) spontaneous preterm birth. We investigated the relations between these defective placentation syndromes and the incidence of Autism Spectrum Disorder (ASD) in offspring. We conducted a population-based cohort study of 1,645,455 non-malformed singleton infants born in Sweden 2000-2016 who were followed for up to 17 years using national registers. We compared ASD rates for children prenatally exposed and unexposed to defective placentation syndromes with use of adjusted hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression. We also conducted sibling-controlled analyses among 1,092,132 full siblings. The association of the syndromes with ASD independent of preterm birth was estimated in mediation analyses. There were 23,810 cases of ASD. In both general cohort and sibling analyses, adjusted HRs (95% CI) of ASD were increased in children of mothers with term preeclampsia combined with SGA [1.5 (1.3, 1.9) and 1.9 (1.1, 3.3), respectively], preterm preeclampsia < 34 weeks [1.8 (1.4, 2.2) and 4.2 (2.1, 8.5), respectively], and spontaneous very or extremely preterm birth (≤ 31 weeks) [2.6 (2.2, 3.0) and 2.4 (1.5, 3.8), respectively]. Placental abruption was associated with increased HR of ASD in general cohort analysis only. The association between preeclampsia and ASD was not fully explained by preterm birth. In conclusion, syndromes linked to defective placentation are associated with increased incidence of ASD in the offspring.

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12. Yarar EZ, Roestorf A, Spain D, Howlin P, Bowler D, Charlton R, Happé F. Aging and autism: Do measures of autism symptoms, co-occurring mental health conditions, or quality of life differ between younger and older autistic adults?. Autism Res;2022 (Jul 5)

Previous research has indicated that autistic adults experience higher rates of co-occurring mental health difficulties and poorer quality of life (QoL) than their non-autistic peers. Little is known, however, about these aspects in older age or whether younger and older autistic adults experience similar patterns This cross-sectional study investigated potential age-related effects on autism symptoms, self-reported mental health, and QoL in younger and older autistic adults (n = 79, aged 19-71 years) compared to a non-autistic control group (n = 57) matched for gender, age and IQ. Results showed that autistic adults had higher levels of self-reported autism symptoms and poorer QoL than controls. There were no significant age effects on autism symptoms or on most self-rated mental health symptoms. However, significantly more autistic adults in the younger versus older group scored above the clinical threshold for anxiety, somatoform disorders and eating disorders. Older autistic adults rated social QoL as significantly better than younger autistic adults; there was no significant age difference in the control group. Self-reported QoL was best predicted by self-ratings of severity of depressive symptoms in both groups. Further research is needed to track autism and co-occurring mental health symptomatology across the lifespan, so that service provision can be tailored accordingly. LAY SUMMARY: Young autistic adults have reported more psychological difficulties and poorer quality of life (QoL) than the general population. We investigated whether these difficulties continue into older age. Autism symptoms and mental health problems were common in autistic adults, with no difference between age groups, except for anxiety, physical and eating problems. Although QoL was poorer in both younger and older autistic compared to non-autistic adults, older autistic adults reported better social QoL than those who were younger.

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13. Zhang Y, Zhang S, Chen B, Jiang L, Li Y, Dong L, Feng R, Yao D, Li F, Xu P. Predicting the symptom severity in autism spectrum disorder based on EEG metrics. IEEE Trans Neural Syst Rehabil Eng;2022 (Jul 5);PP

Autism spectrum disorder (ASD) is associated with the impaired integrating and segregating of related information that is expanded within the large-scale brain network. The varying ASD symptom severities have been explored, relying on their behaviors and related brain activity, but how to effectively predict ASD symptom severity needs further exploration. In this study, we aim to investigate whether the ASD symptom severity could be predicted with electroencephalography (EEG) metrics. Based on a publicly available dataset, the EEG brain networks were constructed, and four types of EEG metrics were calculated. Then, we statistically compared the brain network differences among ASD children with varying severities, i.e., high/low autism diagnostic observation schedule (ADOS) scores, as well as with the typically developing (TD) children. Thereafter, the EEG metrics were utilized to validate whether they could facilitate the prediction of the ASD symptom severity. The results demonstrated that both high-and low-scoring ASD children showed the decreased long-range frontal-occipital connectivity, increased anterior frontal connectivity and altered network properties. Furthermore, we found that the four types of EEG metrics are significantly correlated with the ADOS scores, and their combination can serve as the features to effectively predict the ASD symptom severity. The current findings will expand our knowledge of network dysfunction in ASD children and provide new EEG metrics for predicting the symptom severity.

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