1. Ani C, Ayyash HF, Ogundele MO. Community paediatricians’ experience of joint working with child and adolescent mental health services: findings from a British national survey. BMJ Paediatr Open;2022 (Apr);6(1)

OBJECTIVES: Children and young people (CYP) presenting to paediatric or child and adolescent mental health services (CAMHS) often have needs spanning medical and psychiatric diagnoses. However, joint working between paediatrics and CAMHS remains limited. We surveyed community paediatricians in the UK to inform better strategies to improve joint working with CAMHS. METHODS: We conducted an online survey of community paediatricians through the British Association for Community Child Health (BACCH) on how much joint working they experienced with CAMHS, any hindrances to more collaborative working, and the impact on service users and service provision. This paper is based on thematic analysis of 327 free-text comments by paediatricians. RESULTS: A total of 245 community paediatricians responded to the survey (22% of BACCH members). However, some responses were made on behalf of teams rather than for individual paediatricians. The following were the key themes identified: a strong support for joint working between community paediatrics and CAMHS; an acknowledgement that current levels of joint working were limited; the main barriers to joint working were splintered commissioning and service structures (eg, where integrated care systems fund different providers to meet overlapping children’s health needs); and the most commonly reported negative impact of non-joint working was severely limited access to CAMHS for CYP judged by paediatricians to require mental health support, particularly those with autism spectrum disorder. CONCLUSION: There is very limited joint working between community paediatrics and CAMHS in the UK, which is associated with many adverse impacts on service users and providers. A prointegration strategy that includes joint commissioning of adequately funded paediatric and CAMHS services that are colocated and within the same health management organisations is crucial to improving joint working between paediatrics and CAMHS.

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2. Bearss K, Kim SJ, Locke J. Accessible, Equitable, and Personalized Care for Autistic Individuals. J Clin Med;2022 (Sep 3);11(17)

When it comes to service accessibility for autistic individuals, there exists a pipeline problem […].

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3. Bharat R, Uzaina U, Yadav T, Niranjan S, Kurade P. mHealth apps delivering early intervention to support parents of children with autism: a scoping review protocol. BMJ Paediatr Open;2022 (May);6(1)

OBJECTIVE: This review aims to identify the mhealth apps delivering early intervention to support parents of children with autism spectrum disorders (ASD). We aim to explore the concept, context and methodology of implementation that is, theoretical framework, feasibility, quality of evidence, for such apps. BACKGROUND: To improve outcomes for children with autism, early intervention has been found to be promising. Parental training, parent psychoeducation and parent-mediated intervention are regarded as the gold standard, to achieve early childhood development goals. Digital health technologies like tele-health, web-based services, have been used to deliver this at a reduced cost. There is little evidence about their use and efficacy in empowering parents of children with ASD. INCLUSION CRITERIA: The studies reporting the use of mhealth apps to support parents of children with ASD, in community settings, school settings, special schools, clinics, hospitals or child development centres. There will be no exclusion based on region, gender or sociocultural factors. The types of studies included will be quantitative, qualitative, mixed-methods study designs, case reports, grey literature, systematic reviews, clinical trials and studies reporting feasibility of digital mhealth applications. METHOD: Using the NICE Healthcare Databases Advanced Search, we will search the following databases: MEDLINE, PUBMED, CINAHL, EMBASE, PsycINFO, Cochrane Library, EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect. Furthermore, grey literature will be searched through Google Scholar, ShodhGanga, JSTOR, CORE, EBSCO, DOAJ, BASE. The searches will be limited to the age range of children between 2 and 6 years with ASD, and the date range is from the inception of the database to the current date. The terms for the ASD will be combined with terms for parent, early intervention and digital mhealth to identify eligible studies.

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4. Boorom O, Alviar C, Zhang Y, Muñoz VA, Kello CT, Lense MD. Child language and autism diagnosis impact hierarchical temporal structure of parent-child vocal interactions in early childhood. Autism Res;2022 (Sep 3)

Timing is critical to successful social interactions. The temporal structure of dyadic vocal interactions emerges from the rhythm, timing, and frequency of each individuals’ vocalizations and reflects how the dyad dynamically organizes and adapts during an interaction. This study investigated the temporal structure of vocal interactions longitudinally in parent-child dyads of typically developing (TD) infants (n = 49; 9-18 months; 48% male) and toddlers with ASD (n = 23; 27.2 ± 5.0 months; 91.3% male) to identify how developing language and social skills impact the temporal dynamics of the interaction. Acoustic hierarchical temporal structure (HTS), a measure of the nested clustering of acoustic events across multiple timescales, was measured in free play interactions using Allan Factor. HTS reflects a signal’s temporal complexity and variability, with greater HTS indicating reduced flexibility of the dyadic system. Child expressive language significantly predicted HTS (ß = -0.2) longitudinally across TD infants, with greater dyadic HTS associated with lower child language skills. ASD dyads exhibited greater HTS (i.e., more rigid temporal structure) than nonverbal matched (d = 0.41) and expressive language matched TD dyads (d = 0.28). Increased HTS in ASD dyads occurred at timescales >1 s, suggesting greater structuring of pragmatic aspects of interaction. Results provide a new window into how language development and social reciprocity serve as constraints to shape parent-child interaction dynamics and showcase a novel automated approach to characterizing vocal interactions across multiple timescales during early childhood. LAY SUMMARY: Successful interactions involve conversational partners’ flexibly adapting the timing of their behaviors. We measured the temporal patterns of vocalizations in parent-child interactions of typically developing (TD) and autistic infants/toddlers. While language growth made vocal interaction timing more flexible for TD child-parent dyads, it did not for autistic child-parent dyads who exhibited increased clustering of vocal interactions. Both language and social reciprocity play a role in the timing structure and flexibility of smooth interactions.

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5. Borkhoff CM, Atalla M, Bayoumi I, Birken CS, Maguire JL, Parkin PC. Predictive validity of the Infant Toddler Checklist in primary care at the 18-month visit and developmental diagnosis at 3-5 years: a prospective cohort study. BMJ Paediatr Open;2022 (Jun);6(1)

OBJECTIVE: There is international variation in recommendations regarding developmental screening and growing recognition of the low sensitivity of commonly used developmental screening tools. Our objective was to examine the predictive validity of the Infant Toddler Checklist (ITC) at 18 months to predict a developmental diagnosis at 3-5 years, in a primary care setting. METHODS: We designed a prospective cohort study, recruiting in primary care in Toronto, Canada. Parents completed the ITC at the 18-month visit and reported developmental diagnosis at 3-5 years (developmental delay, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), learning problem). We calculated screening test properties with 95% CIs. We used multivariable logistic regression analyses adjusted for important covariates. RESULTS: In the final sample (n=488), mean age at screening was 18.5 (SD 1.1) months, and at follow-up was 46.6 (SD 10.0) months. At screening, 46 (9.4%) had a positive ITC. At follow-up, 26 (5.3%) had a developmental diagnosis, including: developmental delay (n=22), ASD (n=4), ADHD (n=1), learning problem (n=1); parents of two children each reported two diagnoses (total of 28 diagnoses). Of four children with a diagnosis of ASD at follow-up, three had a positive ITC at 18 months. The ITC specificity (92%, 95% CI: 89% to 94%) and negative predictive value (96%, 95% CI: 95% to 97%) were high; false positive rate was low (8%, 95% CI: 6% to 11%); sensitivity was low (31%, 95% CI: 14% to 52%). There was a strong association between a positive ITC at 18 months and later developmental diagnosis (adjusted OR 4.48, 95% CI: 1.72 to 11.64; p=0.002). CONCLUSION: The ITC had high specificity, high negative predictive value, low false positive rate, and identified children with later developmental delay and ASD. The ITC had low sensitivity, similar to other screening tools underscoring the importance of continuous developmental surveillance at all health supervision visits.

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6. Carson TB, Qiu Y, Liang L, Medina AM, Ortiz A, Condon CA, Ryan N, Ambrosio J, Carcamo K, Miranda D, Palacio-Raine A. Development and validation of a paediatric version of the Khalfa Hyperacusis Questionnaire for children with and without autism. Int J Audiol;2022 (Sep 2):1-9.

OBJECTIVE: Hyperacusis is reported to occur in 3.2-17.1% of the general paediatric population with higher rates in clinical populations such as autism spectrum disorders (ASD). Although hyperacusis is a relatively common form of decreased sound tolerance (DST), no valid paediatric hyperacusis measures are currently available. The purpose of the present study was to develop and validate a paediatric version of the Khalfa Hyperacusis Questionnaire (HQ) as a first step towards filling this measurement gap. DESIGN: A cross-sectional design was used to evaluate therapist opinions of the paediatric version (P-HQ) and to field test the P-HQ in parents of children with and without ASD. Total scores were compared between ASD and non-ASD groups. STUDY SAMPLE: Eleven paediatric occupational and speech therapists with expertise in ASD, 64 parents of children with ASD and 37 parents of children without ASD completed online questionnaires. Psychometric analyses were conducted. RESULTS: A unidimensional construct was found underlying P-HQ and all items displayed sufficient theoretical relevance to hyperacusis and adequate psychometric properties. CONCLUSIONS: The P-HQ demonstrates good internal consistency and shows promise as a potential screening tool for identifying DST in ASD. Further research is warranted to establish normative data and validate cut-off scores.

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7. Clifford P, Gevers C, Jonkman KM, Boer F, Begeer S. The effectiveness of an attention-based intervention for school-aged autistic children with anger regulating problems: A randomized controlled trial. Autism Res;2022 (Aug 31)

Anger regulation is a challenge for children with autism spectrum disorders (ASD). We investigated if attention-based cognitive behavioral treatment, based on mindfulness cognitive therapy (MBCT) and dialectical behavior therapy (DBT), reduces aggressive behavior and improves anger coping in school-aged autistic children (n = 51). Children were randomized to an active-control or a treatment condition. The treatment included nine weekly sessions attention-based individual therapy. Parents in both conditions received three weekly psychoeducation group sessions to heighten awareness of expressed emotion (EE). For aggressive behavior, treatment reduced temper tantrums and arguing. No effect was found on destroying things and physical violence. For anger coping, treatment increased adaptive coping strategies of diffusion and social support seeking, but had no effect on assertion, rumination, and maladaptive coping direct anger out and avoidance. Treatment did not impact secondary outcome measures concerning children’s quality of life (QoL) and parental stress-levels and psychological well-being. In conclusion, school-aged autistic children are able to acquire self-regulation skills reducing temper tantrums and arguing and increasing the use of adaptive anger coping strategies. The intervention shows potential to improve behavior and regulation, but little transfer to other domains. Limitations and future directions involving the child’s social environment, including parents, siblings, and teachers are discussed. LAY SUMMARY: Children on the autism spectrum often show aggressive behavior. Treatment can train children to be more aware of their emotions. This study found that this can help reducing temper tantrums and arguing and increasing some coping skills, though no impact was found on several other domains of aggression and coping.

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8. Dack R, Garstang JJ. Use of melatonin: a single-centre audit. BMJ Paediatr Open;2022 (Feb);6(1)

Sleep disorders in childhood are common. Melatonin is prescribed by UK community paediatricians to treat sleep disorders, but practice is not standardised. This audit reviewed melatonin prescribing within a community paediatric department in a 12-month period. 682 children received melatonin prescriptions; a random sample of 198 records were reviewed. The most common underlying condition was autism spectrum disorder (ASD) in 28%. 41% had no underlying diagnosis when melatonin was initiated and were waiting for neurodevelopmental/ASD assessment. 42% were on melatonin for at least 2 years. Further work is required to optimise melatonin prescribing practice for children and young people.

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9. Dhuga Y, Feeney Y, Gallaher L, White A, Wright J, Banerjee S, Daley S. Developing undergraduate autism education for medical students: a qualitative study. BMJ Paediatr Open;2022 (Aug);6(1)

BACKGROUND: Autistic adults and children experience considerable health inequalities and have high rates of premature mortality, hospital admissions and emergency department visits. This is in part due to a lack of autism awareness in the healthcare and social care workforce. A new educational programme, Time for Autism (TfA), for medical students is being developed to address this challenge. This qualitative study was undertaken to support the development of the new programme in order to (1) understand the medical care experiences of parents of autistic children and (2) assess their views on the acceptability of the new TfA programme and willingness to be involved. METHODS: A convenience sample of 11 parents of autistic children were recruited across the South of England. The ages of the autistic children ranged from 3 to 17 years. Semistructured interviews were completed between October and December 2019. Interview transcripts were analysed using thematic analysis. RESULTS: Three key themes were identified: diagnosis, experiences of doctors and TfA considerations. There was support for and willingness to take part in a dedicated autism education programme for medical students, and constructive feedback to inform and improve its delivery. CONCLUSION: The findings from this study provide insights into the medical care experiences of parents/carers of autistic children. Understanding how parents/carers of autistic children would like medical care to be improved can be used to develop TfA and other autism programmes. Parental/carer support for the development of and involvement in an autism medical education programme enhances the feasibility of the new programme.

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10. D’Mello AM, Frosch IR, Li CE, Cardinaux AL, Gabrieli JDE. Exclusion of females in autism research: Empirical evidence for a « leaky » recruitment-to-research pipeline. Autism Res;2022 (Aug 22)

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. LAY SUMMARY: Despite efforts to increase the representation of autistic females in research, studies consistently enroll small samples of females or exclude females altogether. We find that despite making up almost 50% of the initially recruited sample based upon self-report of community diagnosis, autistic females are disproportonately excluded from research participation as a result of commonly used autism diagnostic measures. In our sample, and several other publically available datasets, reliance on community diagnosis resulted in significantly more equal sex ratios.

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11. Eigsti IM, Fein DA. Insights from losing the autism diagnosis: Autism spectrum disorder as a biological entity. Front Psychiatry;2022;13:972612.

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12. Golan O, Terner M, Israel-Yaacov S, Allison C, Baron-Cohen S. The Autism-Spectrum Quotient-Hebrew version: Psychometric properties of a full and a short form, adapted for DSM-5. Autism;2022 (Sep 2):13623613221117020.

Despite the attempt to diagnose autism at an early age, there are still many individuals who would only get an autism diagnosis in adulthood. For these adults, a questionnaire that could assist in highlighting their need to seek diagnostic assessment is needed. The Autism-Spectrum Quotient is a self-report scale used to assess autistic traits. It was tested cross-culturally, and a short version was recommended to help identify adults who should be referred for an autism assessment. However, its relevance for the up-to-date diagnostic criteria, according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), has not been tested. This study aimed to examine the psychometric properties of the Hebrew version of the Autism-Spectrum Quotient and to create a short version of the Hebrew Autism-Spectrum Quotient, based on items which map on to Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria. Ninety-three autistic adults (24 females), aged 18-51, clinically diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (5th ed.), and 147 comparable controls (34 females) filled out the Hebrew version of the Autism-Spectrum Quotient. Ten clinicians who specialize in diagnosing autism in adults classified the Autism-Spectrum Quotient’s items according to Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria. The short version of the Hebrew Autism-Spectrum Quotient comprised items that best differentiated between adults with and without autism, five items representing each of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnostic domains. The overall probability for participants to be correctly classified as autistic or neurotypical was 86% for the Hebrew version of the Autism-Spectrum Quotient and 88% for the short version of the Hebrew Autism-Spectrum Quotient. We conclude that both versions are reliable and sensitive instruments that can help referring adults for autism assessment.

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13. Hong JS, Singh V, Kalb L, Reetzke R, Ludwig NN, Pfeiffer D, Holingue C, Menon D, Lu Q, Ashkar A, Landa R. Replication study for ADOS-2 cut-offs to assist evaluation of autism spectrum disorder. Autism Res;2022 (Sep 2)

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) has been widely used for ASD assessment. While prior studies investigated sensitivity and specificity of ADOS-2 Modules 1-3, there has been limited research addressing algorithm cut-off scores to optimize ADOS-2 classification. The goal of this study was to assess algorithm cut-off scores for diagnosing ASD with Modules 1-3, and to evaluate alignment of the ADOS-2 classification with the best estimate clinical diagnosis. Participants included 3144 children aged 31 months or older who received ADOS-2 Modules 1-3, as well as the best estimate clinical diagnosis. Five classification statistics were reported for each module: sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (i.e., Receiver Operator Classification Statistic), and these statistics were calculated for the optimal cut-off score. Frequency tables were used to compare ADOS-2 classification and the best estimate clinical diagnosis. Half of the sample received Module 3, 21% received Module 2, and 29% received Module 1. The overall prevalence of ASD was 60%; the male-to-female ratio was 4:1, and half of the sample was non-White. Across all modules, the autism spectrum cut-off score from the ADOS-2 manual resulted in high sensitivity (95%+) and low specificity (63%-73%). The autism cut-off score resulted in better specificity (76%-86%) with favorable sensitivity (81%-94%). The optimal cut-off scores for all modules based on the current sample were within the autism spectrum classification range except Module 2 Algorithm 2. In the No ASD group, 29% had false positives (ADOS-2 autism spectrum classification or autism classification). The ADOS-2 autism spectrum classification did not indicate directionality for diagnostic outcome (ASD 56% vs. No ASD 44%). While cut-off scores of ADOS-2 Modules 1-3 in the manual yielded good clinical utility in ASD assessment, false positives and low predictability of the autism spectrum classification remain challenging for clinicians. LAY SUMMARY: ADOS-2 Modules 1-3 have been widely used for ASD assessment, but there has been limited research on algorithm cut-off scores to optimize ADOS-2 clinical performance. Using a large independent sample, we examined alignment of the ADOS-2 classification with clinicians’ best estimate clinical diagnosis, assessing algorithm cut-off scores. Cut-off scores of ADOS-2 Modules 1-3 in the manual yielded good clinical utility in ASD classification. The optimal cut-off scores based on the current sample were generally within the autism spectrum classification range.

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14. Hsu JW, Tsai SJ, Bai YM, Huang KL, Su TP, Chen TJ, Chen MH. Risk of exposure to prescription opioids in children and adolescents with autism spectrum disorder: A nationwide longitudinal study. Autism Res;2022 (Aug 27)

Whether children and adolescents with autism spectrum disorder (ASD) are more likely to be exposed to prescription opioids than others remains unknown. The Taiwan National Health Insurance Research Database was employed, and 14,849 children and adolescents with ASD and 148,490 age- and sex-matched non-ASD controls were enrolled between 2001 and 2009 and followed up till the end of 2011. Those exposed to prescription opioids during the follow-up period were identified. Patients with ASD were more likely to be exposed to prescription opioids (hazard ratio [HR]: 4.95, 95% confidence interval [CI]: 4.50-5.45), including intravenous or intramuscular opioids (HR: 5.80, 95% CI: 5.23-6.43) and oral or transcutaneous opioids (HR: 2.32, 95% CI: 1.87-2.89), than were non-ASD controls. Furthermore, the ASD cohort had the increased likelihood of cumulative exposure of >14 days (HR: 6.19, 95% CI: 4.91-7.79) and >30 days (HR: 7.17, 95% CI: 5.19-9.90) to prescription opioids compared with the control cohort. ASD was a risk factor for exposure to prescription opioids. Close monitoring of prescription opioid use is necessary for at-risk children and adolescents with ASD, such as those having with or chronic pain. We found that patients with ASD were more likely to be exposed to prescription opioids, including intravenous or intramuscular opioids and oral or transcutaneous opioids, than were non-ASD controls. We suggest that close monitoring of prescription opioid use is necessary for at-risk children and adolescents with ASD, such as those having with or chronic pain.

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15. Hsu TW, Chu CS, Tsai SJ, Hsu JW, Huang KL, Cheng CM, Su TP, Chen TJ, Bai YM, Liang CS, Chen MH. Diagnostic Progression to Schizophrenia: A Nationwide Cohort Study of 11,170 Adolescents and Young Adults with Autism Spectrum Disorder. Psychiatry Clin Neurosci;2022 (Sep 3)

AIMS: Previous studies have suggested an increased risk of developing schizophrenia later in life in children with ASD. This study aims to investigate the diagnosis stability and the potential predictors for progression to schizophrenia in autism spectrum disorder (ASD). METHODS: We recruited 11,170 adolescents (10-19 years) and young adults (20-29 years) with ASD between 2001 and 2010. They were followed up to the end of 2011 to identify newly diagnosed schizophrenia. The Kaplan-Meier method and Cox regression with age as a time scale were employed to estimate incidence rates and the significance of candidate predictors. RESULTS: The progression rate from ASD to schizophrenia was10.26%for 10 years of follow-up. Among 860 progressors, 580 (67.44%)occurred within the first 3 years after a diagnosis of ASD.The identified predictors were age (reported as hazard ratio with 95% confidence interval: 1.13; 1.11-1.15), depressive disorder (1.36; 1.09-1.69), alcohol use disorder (3.05; 2.14-4.35),substance use disorder (1.91; 1.18-3.09),cluster A personality disorder (2.95; 1.79-4.84), cluster B personality disorder (1.86; 1.05-3.28),and a family history of schizophrenia (2.12; 1.65-2.74). CONCLUSION: More than two-thirds of the progressors developed schizophrenia within the first 3 years. Demographic characteristics, physical and psychiatric comorbidities, and psychiatric family history were significant predictors of progression. This article is protected by copyright. All rights reserved.

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16. Jadav N, Bal VH. Associations between co-occurring conditions and age of autism diagnosis: Implications for mental health training and adult autism research. Autism Res;2022 (Aug 27)

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. LAY SUMMARY: In a large sample of independent autistic adults, those diagnosed with ASD after 21 years of age indicated having more psychiatric diagnoses than those diagnosed before 21 years of age. This highlights the importance of considering age of ASD diagnosis in research and underscores a need for autism training in the broader mental health field.

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17. Ketcheson LR, Pitchford EA, Staples KL, MacDonald M, Ulrich DA. Supporting the need for the motor domain to be included in the definition of autism spectrum disorder: A response to Bishop et al.’s critique of Bhat (2021). Autism Res;2022 (Sep 2)

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18. Kunda M, Zhou S, Gong G, Lu H. Improving Multi-Site Autism Classification via Site-Dependence Minimization and Second-Order Functional Connectivity. IEEE Trans Med Imaging;2022 (Sep 2);PP

Machine learning has been widely used to develop classification models for autism spectrum disorder (ASD) using neuroimaging data. Recently, studies have shifted towards using large multi-site neuroimaging datasets to boost the clinical applicability and statistical power of results. However, the classification performance is hindered by the heterogeneous nature of agglomerative datasets. In this paper, we propose new methods for multi-site autism classification using the Autism Brain Imaging Data Exchange (ABIDE) dataset. We firstly propose a new second-order measure of functional connectivity (FC) named as Tangent Pearson embedding to extract better features for classification. Then we assess the statistical dependence between acquisition sites and FC features, and take a domain adaptation approach to minimize the site dependence of FC features to improve classification. Our analysis shows that 1) statistical dependence between site and FC features is statistically significant at the 5% level, and 2) extracting second-order features from neuroimaging data and minimizing their site dependence can improve over state-of-the-art classification results, achieving a classification accuracy of 73%. The code is available at https: //github.com/kundaMwiza/fMRI-site-adaptation.

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19. Mathew NE, Mallitt KA, Masi A, Katz T, Walker AK, Morris MJ, Ooi CY. Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles. Autism Res;2022 (Aug 26)

Diets of children and adolescents on the autism spectrum often differ when compared to their non-autistic peers. Most dietary studies have been limited by small sample sizes and rarely assess the heterogeneity of autism. Addressing this gap, this study compared the anthropometrics, dietary composition, dietary quality, and food variety of 154 Australian children and adolescents on the spectrum and 213 non-autistic children (71 siblings and 142 unrelated controls). Beyond the case-control approach, within-group comparisons assessed the influence of autism clinical presentations and sensory processing styles on body mass index (BMI) and measures of dietary intake among those on the spectrum. In this word first study of diet that included between-group comparisons with non-autistic peers (siblings and an unrelated comparison group) and within-autism group comparisons, we found that children on the spectrum consumed limited variety and lower quality of food and non-autistic siblings also ate comparably higher levels of energy-dense, nutrient poor food, and less diary. This may be due to autistic traits influencing family’s diets or shared sensory sensitivities driving dietary intake. Within the autism group, higher autistic traits were associated with lower BMIs and a specific dietary pattern higher in simple carbohydrates and lower in unprocessed protein. Contrastingly, greater sensitivity to sensory stimuli was associated with a healthier diet. Increased age was linked to more varied diets but also diets higher in saturated fats and energy-dense, nutrient poor foods. Overall, this research highlights that potential mediators of dietary intake, such as familial influences, autistic traits, sensory processing styles, age and sex, need to be considered when assessing diet in the autistic population. LAY SUMMARY: In this study of dietary differences linked to autism, children, and teenagers on the spectrum ate fewer different foods and were less likely to eat recommended amounts of fruits and vegetables when compared to non-autistic siblings and unrelated children and teenagers. There were also family differences, in that those on the spectrum and their siblings ate more unhealthy foods and less dairy. Among those on the spectrum, dietary differences were linked to age, sex, autistic traits and sensory processing styles.

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20. Montenegro MC, Bernal E, Cukier S, Valdez D, Rattazzi A, Garrido G, Rosoli A, Silvestre Paula C, Garcia R, Montiel-Nava C. Age of diagnosis, service access, and rights of autistic individuals in Argentina: Caregivers reports of changes and similarities across time. Front Psychiatry;2022;13:915380.

BACKGROUND: Many countries have developed health initiatives to protect those with disabilities and developmental concerns in the past few years. However, the needs of autistic individuals are still short of being fulfilled. Partially due to limited research expenditure, which would allow bridging the gap between evidence and practice, the long time it takes to implement passed laws, and the limited operationalization of inclusive policies. OBJECTIVE: To quantitatively examine changes in the child’s age at the time of caregiver’s first developmental concerns and age of diagnosis of their autistic child across 5 years. Also, to address challenges experienced by caregivers (e.g., reported service barriers) and the work still needing to be done in Argentina based on caregivers’ reports of their priorities (e.g., ensuring their child receives better services). METHODS: Two independent samples of caregivers of autistic individuals were surveyed by the Red Espectro Autista Latinoamerica (REAL) in 2015 (n = 763) and the World Health Organization (WHO) in 2020 (n = 422). Similar items in both surveys were compared through descriptive inferential analysis and chi-square tests for categorical variables. RESULTS: Compared to the 2015 sample, for the 2020 sample, more caregivers reported an earlier age of first concerns and an earlier age of a professional diagnosis. In the 2020 sample, more children diagnosed before the age of three had a doctor or a teacher noticing the first developmental concern. Also, in this sample, fewer caregivers reported service barriers (e.g., limited availability, waitlist, costs, etc.) and a need for better social support and better health services. However, rates of caregivers indicating a need for more rights for autistic individuals and greater protection of existing rights increased. There was no change in the reported rate of family members who stopped working to care for the autistic individual. For both samples, there was statistically significant differences in individual (physician, teacher, caregiver) noticing first developmental concern and the age of diagnosis, with the majority having a caregiver noticing the first concern. CONCLUSION: The 5 years that separate both samples show an improvement in developmental concerns being noticed, a decrease in age of diagnosis, and an improvement in several service areas such as community awareness. Also, caregivers reported fewer barriers to service accessibility, thus suggesting a positive impact stemming from changes in public policies, non-profit organizations’ work through awareness campaigns, and advocates’ strives toward greater awareness. Nonetheless, a similar proportion of family members reported ceasing working to care for autistic individuals and perceived that the fundamental rights of their autistic children needed to be protected. These results imply that despite better care pathways in Argentina, there are still gaps when attempting to meet the needs of autistic individuals and their families. The present study provides a meaningful understanding of existing gaps and help exemplify the perceived improvements when non-profit agencies and advocates promote increased rights and community awareness in addition to the established laws focusing on ASD.

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21. Nakazato M. Do autism spectrum traits run in severe anorexia nervosa?. Psychiatry Clin Neurosci;2022 (Sep);76(9):415.

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22. Pagni BA, Walsh MJM, Ofori E, Chen K, Sullivan G, Alvar J, Monahan L, Guerithault N, Delaney S, Braden BB. Effects of age on the hippocampus and verbal memory in adults with autism spectrum disorder: Longitudinal versus cross-sectional findings. Autism Res;2022 (Aug 24)

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. LAY SUMMARY: Autistic adults have increased risk of dementia, differences in brain memory structures, and difficulty with memory compared with neurotypical (NT) adults. However, there are no publications that follow the same middle-age autistic adults over time to see how their brain and memory change. Our preliminary findings in a small middle-age autism sample suggest a key memory brain structure, the hippocampus, may shrink faster over 2-3 years compared with NT, and short-term memory may become more challenging for some. Across a broad adult range, autistic adults also had reduced integrity of connections to the hippocampus and greater challenges with long-term memory. In our larger sample across a broad age range, the results did not hint at this aforementioned pattern of accelerated aging. This underscores the importance of more aging research in autism, and especially research where people are followed over time.

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23. Panayotis N, Ehinger Y, Felix MS, Roux JC. State-of-the-art therapies for Rett syndrome. Dev Med Child Neurol;2022 (Sep 3)

Rett syndrome (RTT) is an X-linked neurogenetic disorder caused by mutations of the MECP2 (methyl-CpG-binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re-express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome.

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24. Shalev I, Warrier V, Greenberg DM, Smith P, Allison C, Baron-Cohen S, Eran A, Uzefovsky F. Reexamining empathy in autism: Empathic disequilibrium as a novel predictor of autism diagnosis and autistic traits. Autism Res;2022 (Aug 20)

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.

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