1. Alenezi S, Alsewailem N, Almubaddil BA, Alshaya RS, Alqahtani SMA, Aldossari SA, Alsalhi SM, Alyahya AS. Raising Hopes, Facing Challenges: Understanding Parental Well-Being in the Midst of Autism in Saudi Arabia. Behav Sci (Basel);2024 (Jun 25);14(7)

BACKGROUND: This study aimed to investigate the levels of anxiety, depression, and quality of life among parents of children with autism spectrum disorder. It also compared the difference in these levels between mothers and fathers. Additionally, it quantifies the association between parental anxiety, depression, and quality of life, with various sociodemographic factors. METHODS: This analytical, cross-sectional study was carried out between June and December 2022. An online questionnaire was completed by a sample of 394 parents of children with ASD (autism spectrum disorder) residing in Saudi Arabia. Three scales were used to assess depression, anxiety, and quality of life (QoL), respectively: Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), and World Health Organization Quality of Life-Brief Version (WHOQOL-BREF). RESULTS: Most parents (70.8%) were mothers with an average age of 39 years, typically ranging from 30 to 48 years. Parents’ overall quality of life was 57.72 out of 100, indicating moderate satisfaction. Anxiety levels showed that 32% had mild, 17.8% moderate, and 14.7% severe anxiety. Similarly, depression levels revealed that 34.5% had minimal, 32.2% mild, and 18% moderate depression. Higher anxiety and depression scores were linked to a lower perceived QoL (quality of life). Moreover, the socioeconomic status index (SESi) was significantly and positively correlated with higher depression and lower quality of life. CONCLUSIONS: Autism Spectrum Disorder imposes a strain on parents of the autistic child. The responsibilities linked to the disability amplify the occurrence of depression and anxiety among parents, leading to a diminished quality of life.

Lien vers le texte intégral (Open Access ou abonnement)

2. Barzacchi V, Mangani G, Del Lucchese B, Menici V, Bombonato C, Beani E, Biagioni E, Palla I, Posteraro F, Trieste L, Turchetti G, Sgandurra G, Cioni G, On Behalf Of Tablet Toscana C. TABLET TOSCANA to Develop Innovative Organizational Models for Tele-Rehabilitation in Subjects with Congenital and Acquired Developmental Disabilities: A Wait-List Control Group Trial Protocol. J Clin Med;2024 (Jul 16);13(14)

Background/Objectives: In recent years, the advent of new technologies has fostered their application in neuro-psychomotor and language rehabilitation, particularly since the COVID-19 pandemic. Tele-rehabilitation has emerged as an innovative and timely solution, enabling personalized interventions monitored by clinicians. TABLET TOSCANA project aims to develop innovative tele-rehabilitation organizational models in children, adolescents and young adults with congenital and acquired developmental disabilities, using the Virtual Reality Rehabilitation System (VRRS) Home Kit and the MedicoAmico APP. Methods: The trial is designed according to the CONSORT statement guidelines. The project encompasses three phases: adapting the technologies for pediatric use, validating them through a wait-list study, and analyzing feasibility and effectiveness data to define new organizational models. A randomized wait-list-control study with 100 subjects aged 6 to 30 years will compare tele-rehabilitation versus prosecution of standard care. Discussion: Although literature highlights tele-rehabilitation benefits such as improved access, cost savings, and enhanced treatment adherence, practical implementation remains limited (i.e., the definition of standardized procedures). TABLET TOSCANA project seeks to address these gaps by focusing on multi-domain treatments for neurodevelopmental disabilities and emphasizing the integration of tele-rehabilitation into local health services. Conclusion: The project aims to improve the continuity and intensity of care through innovative models that integrate tele-rehabilitation into local health services. The results could inform healthcare policies and promote the development of innovative and collaborative models of care, paving the way for more effective and widespread tele-rehabilitation solutions and fostering collaborative networks among professionals.

Lien vers le texte intégral (Open Access ou abonnement)

3. Blue CM, Wong SJ, Dodson K. Auditory brainstem response findings in autism spectrum disorder speech delay population. Am J Otolaryngol;2024 (Jul 20);45(5):104417.

OBJECTIVES: Evaluate pediatric auditory brainstem response (ABR) findings in children with Autism Spectrum Disorder (ASD) after the 2013 DSM-5 update. STUDY DESIGN: This was an IRB-approved, six-year retrospective chart review evaluating ABR results from pediatric patients with speech delay. Diagnosis of ASD and other neurodevelopmental abnormalities were collected for patient stratification. METHODS: From 2017 to 2023, 148 pediatric patients with speech delay were identified through diagnosis of speech delay and underwent ABR testing. Patients were then separated into two groups: Neurotypical (N = 79) and ASD (N = 69). ABR results were obtained through chart review and waveform and interpeak latency (IPL) results were recorded. Differences in waveform and IPL results were determined via Pearson’s chi-square test, with multivariate analysis accounting for race, sex, and age. RESULTS: 28 patients with ASD (40.6 %) had at least one waveform/IPL prolongation. Analysis showed an increased incidence of waveform III (p = 0.028) and IPL III-V (p = 0.03) prolongation in the ASD group compared to their neurotypical counterparts. Waveform III prolongation was noted more in females with ASD (p = 0.001) than in males. No statistically significant difference when comparing race and age was found, except in the 2-3 age range (p = 0.003). CONCLUSIONS: There were higher percentages of prolongation for all waveforms and IPLs in the ASD group versus neurotypical, though not as high as previously reported. Race and age did not appear to be factors in ABR findings though more data is needed to make clinical associations.

Lien vers le texte intégral (Open Access ou abonnement)

4. Blum K, Bowirrat A, Sunder K, Thanos PK, Hanna C, Gold MS, Dennen CA, Elman I, Murphy KT, Makale MT. Dopamine Dysregulation in Reward and Autism Spectrum Disorder. Brain Sci;2024 (Jul 22);14(7)

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition and by repetitive stereotyped behaviors. These manifestations are variable between individuals, and ASD pathogenesis is complex, with over a thousand implicated genes, many epigenetic factors, and multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system is held to play a key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving a wide array of mesolimbic loci, neurotransmitters and receptor subtypes, and neuronal variants. How altered DA signaling may constitute a downstream convergence of the manifold causal origins of ASD is not well understood. A clear working framework of ASD pathogenesis may help delineate common stages and potential diagnostic and interventional opportunities. Hence, we summarize the known natural history of ASD in the context of emerging data and perspectives to update ASD reward signaling. Then, against this backdrop, we proffer a provisional framework that organizes ASD pathogenesis into successive levels, including (1) genetic and epigenetic changes, (2) disrupted mesolimbic reward signaling pathways, (3) dysregulated neurotransmitter/DA signaling, and finally, (4) altered neurocognitive and social behavior and possible antagonist/agonist based ASD interventions. This subdivision of ASD into a logical progression of potentially addressable parts may help facilitate the rational formulation of diagnostics and targeted treatments.

Lien vers le texte intégral (Open Access ou abonnement)

5. Cai XY, Wang XT, Guo JW, Xu FX, Ma KY, Wang ZX, Zhao Y, Xie W, Schonewille M, De Zeeuw C, Chen W, Shen Y. Aberrant outputs of cerebellar nuclei and targeted rescue of social deficits in an autism mouse model. Protein Cell;2024 (Jul 27)

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also non-motor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.

Lien vers le texte intégral (Open Access ou abonnement)

6. Carpita B, Nardi B, Bonelli C, Pascariello L, Massimetti G, Cremone IM, Pini S, Palego L, Betti L, Giannaccini G, Dell’Osso L. Platelet Levels of Brain-Derived Neurotrophic Factor in Adults with Autism Spectrum Disorder: Is There a Specific Association with Autism Spectrum Psychopathology?. Biomedicines;2024 (Jul 10);12(7)

To date, although several studies have investigated the circulating levels of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorder (ASD), only a few authors have addressed their evaluation in adults. Furthermore, an important limitation of these studies lies in the fact that circulating BDNF is stored in platelets and released into the circulation when needed. To the best of our knowledge, a very limited number of studies have related peripheral BDNF values to platelet counts, and yet no study has evaluated intra-platelet BDNF levels in adults with ASD. In this framework, the aim of the present work is to pave the way in this field and evaluate platelet BNDF levels in adult ASD patients, as well as their correlation with autistic symptoms and related psychopathological dimensions. We recruited 22 ASD and 22 healthy controls, evaluated with the Adult autism subthreshold spectrum (AdAS Spectrum), the Social Anxiety Spectrum-self report (SHY-SR), the Trauma and loss spectrum-self report (TALS-SR), the Work and Social Adjustment Scale (WSAS), and the Mood Spectrum-self report for suicidality. Intra-platelet BDNF levels were also assessed. The results highlighted lower BDNF levels in the ASD group; moreover, AdAS Spectrum and WSAS total score as well as AdAS Spectrum Restricted interest and rumination, WSAS Private leisure activities, TALS-SR Arousal, and SHY-SR Childhood domains were significant negative predictors of platelet BDNF levels.

Lien vers le texte intégral (Open Access ou abonnement)

7. Carpita B, Nardi B, Giovannoni F, Parri F, Cerofolini G, Bonelli C, Massimetti G, Pellecchia E, Pini S, Cremone IM, Dell’Osso L. Assessing Autistic Traits, Hikikomori Tendencies, Pathological Videogaming, and Eating Disorders in University Students: Are Pathological Videogaming and Eating Disorders Gender-Specific Manifestations of the Autism Spectrum?. Brain Sci;2024 (Jul 17);14(7)

In the previous literature, specific attention has been paid to investigate autism spectrum symptoms and traits in university students. In this framework, we aimed to evaluate the presence and correlates of autistic traits, hikikomori tendencies, altered eating behaviors, and pathological videogaming in a sample of Italian university students enrolled in bachelor’s degree courses. A total of 1192 students were recruited via an online survey and assessed with the Hikikomori Questionnaire-25, the Adult Autism Subthreshold Spectrum Questionnaire, the Eating Attitude test-26, and the Assessment of Internet and Computer Game Addiction. Our results highlighted significant differences in the prevalence of autistic traits, social withdrawal tendencies, altered eating habits, and pathological videogame use in university students based on gender, age, parents’ level of instruction, and field of study. A significant effect of the presence of autistic traits and gender on the scores obtained with the other questionnaires was reported. Our results not only support the role of autistic traits as a vulnerability factor for the development of a set of psychopathological conditions but also suggest that gender could modulate this vulnerability, supporting the hypothesis of gender-specific phenotypes in the autism spectrum.

Lien vers le texte intégral (Open Access ou abonnement)

8. Chojnicka I, Wawer A. Analysis of Autistic Adolescents’ Essays Using Computer Techniques. J Autism Dev Disord;2024 (Jul 27)

PURPOSE: Challenges associated with narrative discourse remain consistently observable across the entire spectrum of autism. We analyzed written narratives by autistic and non-autistic adolescents and aimed to investigate narrative writing using quantitative computational methods. METHODS: We employed Natural Language Processing techniques to compare 333 essays from students in the final eighth grade of primary school: 195 written by autistic and 138 by non-autistic participants. RESULTS: Autistic students used words with a positive emotional polarity statistically less frequently (p < .001), and their stories were less abstract (p < .001) than those written by peers from the non-autistic group. However, autistic adolescents wrote more complex stories in terms of readability than participants from the non-autistic group (p < .001). The writing competencies assessed by teachers did not differ significantly between the two groups. CONCLUSION: Findings suggest that written narratives by autistic individuals may exhibit characteristics similar to those detected by computational methods in spoken narratives. Collecting data from national exams and its potential usefulness in distinguishing autistic individuals could pave the way for future large-scale and cost-effective epidemiological studies on autism.

Lien vers le texte intégral (Open Access ou abonnement)

9. Conrad CE, Jørgensen R, Amstrup C, Gottschau TE, Thomsen PH, Lauritsen MB. « It Seems Much More Enjoyable Now »: Parental Perception of Relational Change from Participating in Paediatric Autism Communication Therapy (PACT). Children (Basel);2024 (Jul 10);11(7)

OBJECTIVES: This qualitative study aims to examine parental experiences of feasibility and relational changes from participating in the Paediatric Autism Communication Therapy (PACT) intervention. METHODS: Thirteen parents of children diagnosed with autism spectrum disorder (mean age 3.89 years) participated in semi-structured interviews. Thematic analysis was performed, inspired by an abductive approach informed by the theories of the attachment system, the caregiving system and mentalisation. RESULTS: Three overarching themes were identified: the struggle of fitting PACT into everyday life, the fruit of relational connection and the cascading relational effects of PACT. Parents were challenged regarding finding time for the intervention but adapted PACT to their individual needs and possibilities. All parents experienced relational improvement, and a cycle of positive relational change through PACT was identified. CONCLUSIONS: This study has several clinical implications. Therapists and clinics offering PACT interventions should encourage and support parents in their individual journey of implementing PACT into their everyday lives. Some of the parents described improvements in parental mentalisation, child attachment and mutual enjoyment in the parent-child relationship. Children with autism could benefit from parents increasing their sensitivity when caregiving, and clinicians may through interventions such as PACT facilitate this development.

Lien vers le texte intégral (Open Access ou abonnement)

10. Cozzi G, Zago A, Poropat F, Rabach I, Barbi E, Amaddeo A. Continuous Infusion of Dexmedetomidine for Maintenance of Sedation in an Aggressive Adolescent with Autism Spectrum Disorder in the Emergency Department. Children (Basel);2024 (Jul 9);11(7)

BACKGROUND: The treatment of aggressive behavior and agitation in pediatric patients with autism spectrum disorder (ASD) in the emergency department is topical and challenging. CASE PRESENTATION: We described an adolescent with autism spectrum disorder treated ten times in the pediatric emergency department for severe episodes of aggressiveness and agitation. After resolving the acute phase of these behavioural crises, sedation was maintained with a continuous infusion of dexmedetomidine to prevent the resurgence of agitation and to organize discharge properly, considering the family’s needs. The continuous infusion of dexmedetomidine allowed the patient to remain asleep most of the time during his stay at the emergency department. No adverse events were recorded. CONCLUSIONS: The continuous infusion of dexmedetomidine could represent a safe and valuable tool to facilitate the permanence of the patient in the PED.

Lien vers le texte intégral (Open Access ou abonnement)

11. Daida A, Oana S, Nadkarni D, Espiritu BL, Edmonds BD, Stanecki C, Samuel AS, Rao LM, Rajaraman RR, Hussain SA, Matsumoto JH, Sankar R, Hannauer PS, Nariai H. Overnight EEG to Forecast Epilepsy Development in Children with Autism Spectrum Disorders. J Pediatr;2024 (Jul 27):114217.

OBJECTIVE: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). STUDY DESIGN: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule (ADOS) data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. RESULTS: Among 151 patients, 17.2% (n=26) developed unprovoked seizures (Sz group), while 82.8% (n=125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs. 20.0%, p=0.01). The Sz group also exhibited a greater frequency of slowing (42.3% vs. 13.6%, p < 0.01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, p=0.01) or any slowing (HR 2.78, 95% CI 1.02-7.58, p=0.046 significantly increased the risk of developing unprovoked seizures. CONCLUSION: Long-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.

Lien vers le texte intégral (Open Access ou abonnement)

12. De Domenico C, Di Cara M, Piccolo A, Settimo C, Leonardi S, Giuffrè G, De Cola MC, Cucinotta F, Tripodi E, Impallomeni C, Quartarone A, Cucinotta F. Exploring the Usefulness of a Multi-Sensory Environment on Sensory Behaviors in Children with Autism Spectrum Disorder. J Clin Med;2024 (Jul 16);13(14)

Background: Autism spectrum disorder (ASD) is a complex neurological development with social and communication deficits and sensory abnormalities. Sensory problems have a significant impact on daily life. Multisensory environments (MSEs), such as Snoezelen(®) rooms, offer controlled sensory stimulation. This study aims to evaluate the effect of MSE intervention with self-controlled sensory interactions on adaptive developmental skills and sensory responses in preschool ASD children. Methods: This pilot study was single-blind, randomized, controlled, and adhered to the CONSORT guidelines. Twenty participants were recruited and randomized into two groups: the control group (CG) underwent treatment as usual (TAU) with individual rehabilitation sessions of psychomotor therapy. The experimental group (EG) underwent TAU integrated with the use of an MSE. Developmental abilities and severity levels were assessed, pre-post, with the Psychoeducational Profile, Third Edition (PEP-3) and the Second Edition Childhood Autism Rating Scale (CARS-2). Results: A significant difference in taste, smell, and tactile behaviors according to the CARS-2, as well as in gross motor skills according to the PEP-3, was observed in the EG. Conclusions: This pilot study suggests that MSE-integrated intervention may be a valid strategy to improve self-management of the sensory profile in autistic individuals. Further studies are needed to better identify the intervention methodology and effectiveness.

Lien vers le texte intégral (Open Access ou abonnement)

13. Draudvilienė L, Draudvila J, Stankevičiūtė S, Daniusevičiūtė-Brazaitė L. Two Physiotherapy Methods to Improve the Physical Condition of Children with Autism Spectrum Disorder. Children (Basel);2024 (Jun 28);11(7)

This study presents two simple physiotherapy programs that were implemented for five weeks and showed positive changes in balance, coordination, and motor skills in kindergarteners with ASD. Physiotherapy programs in a gym and games on a smart board with balance plates and an unstable base were applied to improve the physical condition of children with ASD. Thirty children with ASD (4-6 years old) attending special needs kindergarten were enrolled in the study. Three tests were used to assess participants’ physical condition before and after the study: the modified Berg Balance Scale, the Imbalance Coordination Sample, and the Bruininks-Oseretsky Motor Proficiency Test (BOTMP). The resulting mean change, calculated from each group’s scores, shows that the participants who received physical therapy sessions at the smart board had the greatest change of 1.58 points. It shows that the opportunity to play games on a smart board motivates children with ASD to work harder; therefore, it is a simple and easy way to engage children in different types of physical exercise. A slightly smaller change of 1.51 was obtained in the group that received gym sessions. However, working in the gym was more psychologically challenging for the children with ASD due to their lack of desire and motivation. Both methods are relatively simple and easy to apply at home; therefore, parents can make a significant contribution to improving children’s physical condition and that can be an effective tool to assist these individuals with activities in daily life.

Lien vers le texte intégral (Open Access ou abonnement)

14. Erickson CA, Perez-Cano L, Pedapati EV, Painbeni E, Bonfils G, Schmitt LM, Sachs H, Nelson M, De Stefano L, Westerkamp G, de Souza ALS, Pohl O, Laufer O, Issachar G, Blaettler T, Hyvelin JM, Durham LA. Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD. Biomedicines;2024 (Jun 27);12(7)

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1’s mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Lien vers le texte intégral (Open Access ou abonnement)

15. Feng Y, Huang X, Zhao W, Ming Y, Zhou Y, Feng R, Xiao J, Shan X, Kang X, Duan X, Chen H. Association among internalizing problems, white matter integrity, and social difficulties in children with autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry;2024 (Jul 27):111109.

Autism spectrum disorder (ASD) is characterized by social difficulties and often accompanied by internalizing and externalizing problems, which are frequently overlooked. Here, we examined and compared fractional anisotropy (FA) between 79 children with ASD (aged 4-7.8 years) and 70 age-, gender-, and handedness- matched typically developing controls (TDCs, aged 3-7.2 years). We aimed to explore the relationship among social difficulties, internalizing and externalizing problems, and brain structural foundation (characterized by white matter integrity). Compared with the TDCs, the children with ASD exhibited more severe internalizing and externalizing problems, which were positively correlated with social difficulties. Reduced FA values were observed in specific white matter tracts that integrate a fronto-temporal-occipital circuit. In particular, the FA values within this circuit were negatively correlated with internalizing problems and SRS-TOTAL scores. Mediation analysis revealed that internalizing problems mediated the relationship between the FA values in the left middle longitudinal fasciculus (L-MdLF) and corpus callosum forceps major (CCM) and social difficulties in children with ASD. These findings contribute to our understanding of social difficulties, internalizing and externalizing problems, and white matter integrity in children with ASD and highlight internalizing problems as a mediator between social difficulties and white matter integrity.

Lien vers le texte intégral (Open Access ou abonnement)

16. Focaroli V, Taffoni F, Velardi A, Caravale B, Keller F. Object Exploration and Manipulation in Infants at Typical vs. Elevated Likelihood for ASD: A Review. Children (Basel);2024 (Jul 5);11(7)

The present review considers the growing body of literature on fine motor skills in infants at elevated genetic likelihood (EL) for autism spectrum disorder (ASD). This area of study aims to identify crucial motor markers associated with the disorder, facilitating earlier and more accurate identification of ASD, using various experimental methodologies, including standardized assessments, observational measures, and technological tools. The reviewed evidence revealed distinct developmental trajectories in EL infants, marked by differences in fine motor skills and exploratory behaviors compared to typically developing infants. We discuss the developmental trajectory of fine motor skills in infants and their predictive value for later ASD diagnosis, highlighting the significance of fine motor skills as early indicators of ASD risk in infants and emphasizing the need for further research to elucidate their predictive value and underlying mechanisms.

Lien vers le texte intégral (Open Access ou abonnement)

17. Giua G, Strauss B, Lassalle O, Chavis P, Manzoni OJ. Adaptive group behavior of Fragile X mice in unfamiliar environments. Prog Neuropsychopharmacol Biol Psychiatry;2024 (Jul 27):111111.

Fragile X Syndrome (FXS) stands out as a prominent cause of inherited intellectual disability and a prevalent disorder closely linked to autism. FXS is characterized by substantial alterations in social behavior, encompassing social withdrawal, avoidance of eye contact, heightened social anxiety, increased arousal levels, language deficits, and challenges in regulating emotions. Conventional behavioral assessments primarily focus on short-term interactions within controlled settings. In this study, we conducted a comprehensive examination of the adaptive group behavior of Fmr1 KO male mice over a three-day period, without introducing experimental interventions or task-based evaluations. The data unveiled intricate behavioral anomalies, with the most significant changes manifesting during the initial adaptation to unfamiliar environments. Notably, certain behaviors exhibited a gradual return to typical patterns over time. This dynamic Fmr1 KO phenotype exhibited heightened activity, featuring increased exploration, amplified social interest, and an unconventional approach to social interactions characterized by a higher frequency of shorter engagements. These findings contribute to the growing understanding of social behavior in individuals with FXS and underscore the significance of comprehending their adaptive responses in various environmental contexts.

Lien vers le texte intégral (Open Access ou abonnement)

18. Green CC, Smith J, Bent CA, Chetcuti L, Uljarević M, Benson PR, Hudry K. Predictors of Change in Wellbeing and Mental Health of Parents of Autistic Pre-Schoolers. J Autism Dev Disord;2024 (Jul 26)

Parenting is a rewarding experience but is not without its challenges. Parents of Autistic children face additional challenges, and as a result can experience lower levels of wellbeing and more mental health problems (i.e., depression, anxiety, stress). Previous studies have identified concurrent correlates of wellbeing and mental health. However, few have investigated predictors of subsequent wellbeing and mental health, or of change over time, among parents of pre-school aged autistic children. We examined child-, parent-, and family/sociodemographic factors associated with change in parents’ mental health and wellbeing across three timepoints (spanning approximately one year) among 53 parents of Autistic pre-schoolers (M = 35.48, SD = 6.36 months. At each timepoint, parents reported lower wellbeing and greater mental health difficulties compared to normative data. There was no significant group-level change over time in parent outcomes. However, individual variability in short-term (~ 5 months) wellbeing and mental health change was predicted by a combination of child- and parent-related factors, while variability in medium-term (~ 10 months) change was predicted by parent factors alone. Parents’ description of their child and their relationship predicted change in both wellbeing and mental health. Furthermore, participating in a parent-mediated intervention (available to a subgroup) was a significant predictor of change in wellbeing. Our findings highlight potentially modifiable factors (e.g., learning healthier coping strategies) that may positively impact both short- and medium-term change in parental outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

19. Gural I, Cividini-Motta C, Del Vecchio ML, Risse MR. Evaluating the Effects of Self-Monitoring of Performance with a Peer Component on Disruptive Behavior and Task Completion of Children with Autism Spectrum Disorder. Behav Sci (Basel);2024 (Jun 28);14(7)

Self-monitoring (SM) is a widely used intervention to address a myriad of problem behaviors exhibited by individuals with autism spectrum disorder (ASD) and other disabilities (e.g., specific learning disability). SM of performance (SMP) interventions have been effective in increasing task completion and on-task behaviors in the general education setting. However, most of the research on SM interventions has been completed in a school setting, and few have evaluated the inclusion of a peer mediator component within a SM treatment package. Therefore, the purpose of this study was to evaluate the effects of a SMP intervention on disruptive behavior and task completion in three children with ASD. This study extends previous research by incorporating a peer mediator component, including children with ASD, and implementing the intervention in a clinic setting. The results show that the SM treatment package was effective, as the level of disruptive behavior and task completion improved for all three participants compared to baseline levels.

Lien vers le texte intégral (Open Access ou abonnement)

20. Horen NM, Sayles J, McDermott K, Sippel-Klug K, Drake-Croft J, Long T. Infant and Early Childhood Mental Health (IECMH) and Early Childhood Intervention: Intentional Integration. Int J Environ Res Public Health;2024 (Jul 3);21(7)

Infant and Early Childhood Mental Health (IECMH) is a multidisciplinary field of inquiry, practice, and policy concerned with enhancing the social-emotional competence of infants and young children. Early Childhood Intervention (ECI) is a system of services that supports infants and toddlers with disabilities and their families. ECI providers promote a child’s development in all domains, including social-emotional. The purpose of this paper is to describe how two systems, Early Childhood Intervention and Infant Early Childhood Mental Health, collaborate when serving children who have developmental delays or disabilities and their families and other caregivers. We will discuss two models used to promote social-emotional development, the Pyramid Model and IECMH Consultation, and provide three examples that demonstrate how ECI and IECMH intersect at both the family, classroom, and system levels.

Lien vers le texte intégral (Open Access ou abonnement)

21. Jagadapillai R. Atypical Autism: Causes, Diagnosis and Support. Medicina (Kaunas);2024 (Jul 18);60(7)

Autism spectrum disorder (ASD) is a group of neurobehavioral disorders defined by persistent deficits in social communication and social interactions with repetitive behaviors, and it is typically diagnosed within the first three years of life […].

Lien vers le texte intégral (Open Access ou abonnement)

22. Liu MH, Chiang FM, Chen CT, Yang HC, Chen KL. Development and Psychometric Examination of a New Social Competence Outcome Measure for Children with Autism Spectrum Disorder: The Observational Social Competence Assessment. J Autism Dev Disord;2024 (Jul 27)

Current assessments of social competence for children with autism spectrum disorder (ASD) are mostly designed for screening or diagnosis, not for measuring outcomes. This study aimed to develop a professional-administrated outcome measure, the Observational Social Competence Assessment (OSCA), and examine its psychometric properties. The OSCA was constructed based on a multidimensional view of social competence (i.e., social skill elements, social reciprocity, and social adjustment). For psychometric evaluation, 89 children with ASD between 3 and 12 years (mean = 70.69 months, SD = 15.31) were assessed with the OSCA and with assessments of ASD symptoms, verbal comprehension ability, and adaptive function. The results show that the OSCA has good internal consistency (Cronbach’s α = 0.820-0.954), test-retest reliability (intraclass correlation coefficients [ICC] = 0.917-0.960), and inter-rater reliability (ICC = 0.905-0.974). The OSCA also has good convergent (r = 0.508-0.703, p < 0.01) and divergent validity (r = 0.105, p = 0.496), as well as good responsiveness to changes in the social adjustment dimension (Cohen's d = 1.26 and standardized response mean [SRM] = 1.92). Conclusively, these results show that the OSCA is sufficiently reliable, valid and responsive to be applied as an outcome measure of social competence in children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

23. Manning C. Visual processing and decision-making in autism and dyslexia: Insights from cross-syndrome approaches. Q J Exp Psychol (Hove);2024 (Jul 27):17470218241264627.

Atypical visual processing has been reported in developmental conditions like autism and dyslexia, and some accounts propose a causal role for visual processing in the development of these conditions. However, few studies make direct comparisons between conditions, or use sufficiently sensitive methods, meaning that it is hard to say whether atypical visual processing tells us anything specific about these conditions, or whether it reflects a more general marker of atypical development. Here I review findings from two computational modelling approaches (equivalent noise and diffusion modelling) and related electroencephalography (EEG) indices which we have applied to data from autistic, dyslexic and typically developing children to reveal how the component processes involved in visual processing and decision-making are altered in autism and dyslexia. The results identify both areas of convergence and divergence in autistic and dyslexic children’s visual processing and decision-making, with implications for influential theoretical accounts such as weak central coherence, increased internal noise, and dorsal-stream vulnerability. In both sets of studies, we also see considerable variability across children in all three groups. To better understand this variability, and further understand the convergence and divergence identified between conditions, future studies would benefit from studying how the component processes reviewed here relate to transdiagnostic dimensions, which will also give insights into individual differences in visual processing and decision-making more generally.

Lien vers le texte intégral (Open Access ou abonnement)

24. May D, Kponee-Shovein K, Neul JL, Percy AK, Mahendran M, Downes N, Chen G, Watson T, Pichard DC, Kennedy M, Lefebvre P. Characterizing the journey of Rett syndrome among females in the United States: a real-world evidence study using the Rett syndrome natural history study database. J Neurodev Disord;2024 (Jul 26);16(1):42.

BACKGROUND: With the advent of the first targeted therapy for Rett Syndrome (RTT), a comprehensive assessment of the journey of RTT is needed to elucidate on present unmet needs in this population. This study characterized females with RTT in the United States and their disease journey with respect to longitudinal treatment patterns, RTT-related outcomes, and changes in disease severity. METHODS: This retrospective cohort study used registry data of females with RTT from the 5211 RTT Natural History Study (RNHS) (November 2015-July 2021). Pharmacological and supportive therapy use, RTT-related outcomes, and RTT severity, as measured by the Clinical Severity Scale and Motor Behavioral Assessment scale, were evaluated following the first RNHS visit. Analyses were conducted overall and in subgroups by RTT type (classic and atypical RTT) and age at first visit (pediatric and adult). RESULTS: A total of 455 females with RTT were included in the study, of whom 90.5% had classic RTT and 79.8% were pediatric individuals. Over a median follow-up of 4 years, use of pharmacological therapies, including prokinetic agents (42.7% vs. 28.3%), and supportive therapies, including physical therapy (87.3% vs. 40.2%) and speech-language therapy (86.8% vs. 23.9%), were more common in pediatric than adult individuals (all p < 0.05). Nearly half (44.6%) of all individuals had a hospital or emergency room visit, with a higher proportion of visits in individuals with classic RTT than atypical RTT and pediatric than adult individuals (both p = 0.001). An increasing trend in clinical severity was observed in pediatric individuals (mean change per year: 0.24; 95% confidence interval [CI]: 0.03, 0.44), while an increasing trend in motor-behavioral dysfunction was observed in pediatric individuals (mean change per year: 1.12; 95% CI: 0.63, 1.60) and those with classic RTT (mean change per year: 0.97; 95% CI: 0.53, 1.41). CONCLUSIONS: Findings from this study highlight the considerable burden of RTT across disease subtype and age. Despite reliance on supportive therapies and healthcare encounters, individuals with RTT experience increasing disease severity and motor-behavioral dysfunction in childhood and adolescence, underscoring the unmet needs of this population and the value of early intervention to manage RTT in the long-term.

Lien vers le texte intégral (Open Access ou abonnement)

25. Mayes SD, Pardej SK, Waschbusch DA. Oppositional Defiant Disorder in Autism and ADHD. J Autism Dev Disord;2024 (Jul 27)

Our study compared oppositional defiant disorder (ODD) in children with autism to ADHD-Combined presentation and ADHD-Inattentive presentation. Mothers of 2,400 children 3-17 years old with autism and/or ADHD completed the Pediatric Behavior Scale. ADHD-Combined was most strongly associated with ODD, with an ODD prevalence of 53% in children with ADHD-Combined only. When autism was added to ADHD-Combined, prevalence increased to 62% and the ODD score increased significantly. Autism+ADHD-Inattentive, Autism Only, and ADHD-Inattentive Only had ODD prevalences of 28%, 24% and 14%. In each diagnostic group, ODD had the same two factors (irritable/angry and oppositional/defiant); demographic differences between children with and without ODD were few; and correlations between ODD and conduct problems were large, correlations with depression were medium, and correlations with anxiety were small. However, ODD scores differed significantly between groups (Autism+ADHD-Combined > ADHD-Combined Only > Autism+ADHD-Inattentive and Autism Only > ADHD-Inattentive Only). The irritable/angry ODD component was greater in Autism+ADHD-Combined than in ADHD-Combined Only, whereas the oppositional/defiant component did not differ between the two groups. Autism was a significant independent risk factor for ODD, particularly the irritable/angry ODD component, but ADHD-Combined was the strongest risk factor. Therefore, the high co-occurrence of ADHD-Combined in autism (80% in our study) largely explains the high prevalence of ODD in autism. ADHD-Combined, autism, and ODD are highly comorbid (55-90%). Clinicians should assess all three disorders in referred children and provide evidence-based interventions to improve current functioning and outcomes for children with these disorders and reduce family and caretaker stress.

Lien vers le texte intégral (Open Access ou abonnement)

26. McConkey R, Allen S, Mlambo C, Kambarami P, Martin K. Creating Family-Centred Support for Children with Developmental Disabilities in Africa: Examples of Local Community Interventions. Int J Environ Res Public Health;2024 (Jul 16);21(7)

Preschoolers with disabilities and their family caregivers are overlooked by many public health initiatives, especially in low-income countries. Yet they can benefit from early intervention to promote their development soon after birth and to provide a better quality of life for their families. In this paper, we describe how a community-based approach has been implemented with minimal funding in two areas in Zimbabwe: a township in Harare and in rural areas of Manicaland Province. Our aim in sharing this information-allied with references to research studies recently undertaken in Africa-is that it will enable similar support to be replicated in other communities by local personnel. A logic model is used to describe the situation in which the two projects work, the various inputs they have provided to their community, and the different forms of support they have offered to the children and their caregivers. The project outputs are listed in terms of the number of beneficiaries helped and the activities undertaken. The outcomes achieved for the children, families, and communities are reported. The sustainability and extensions of community-based projects to address unmet needs are discussed. The main conclusion is that disadvantaged communities can be energised to address the needs of their most marginalised residents.

Lien vers le texte intégral (Open Access ou abonnement)

27. Mehawej C, Maalouf JE, Abdelkhalik M, Mahfouz P, Chouery E, Megarbane A. CNV Analysis through Exome Sequencing Reveals a Large Duplication Involved in Sex Reversal, Neurodevelopmental Delay, Epilepsy and Optic Atrophy. Genes (Basel);2024 (Jul 10);15(7)

BACKGROUND: Duplications on the short arm of chromosome X, including the gene NR0B1, have been associated with gonadal dysgenesis and with male to female sex reversal. Additional clinical manifestations can be observed in the affected patients, depending on the duplicated genomic region. Here we report one of the largest duplications on chromosome X, in a Lebanese patient, and we provide the first comprehensive review of duplications in this genomic region. CASE PRESENTATION: A 2-year-old female patient born to non-consanguineous Lebanese parents, with a family history of one miscarriage, is included in this study. The patient presents with sex reversal, dysmorphic features, optic atrophy, epilepsy, psychomotor and neurodevelopmental delay. Single nucleotide variants and copy number variants analysis were carried out on the patient through exome sequencing (ES). This showed an increased coverage of a genomic region of around 23.6 Mb on chromosome Xp22.31-p21.2 (g.7137718-30739112) in the patient, suggestive of a large duplication encompassing more than 60 genes, including the NR0B1 gene involved in sex reversal. A karyotype analysis confirmed sex reversal in the proband presenting with the duplication, and revealed a balanced translocation between the short arms of chromosomes X and 14:46, X, t(X;14) (p11;p11) in her/his mother. CONCLUSIONS: This case highlights the added value of CNV analysis from ES data in the genetic diagnosis of patients. It also underscores the challenges encountered in announcing unsolicited incidental findings to the family.

Lien vers le texte intégral (Open Access ou abonnement)

28. Milojevic S, Ghosh A, Makevic V, Stojkovic M, Capovilla M, Tosti T, Budimirovic D, Protic D. Circadian Rhythm and Sleep Analyses in a Fruit Fly Model of Fragile X Syndrome Using a Video-Based Automated Behavioral Research System. Int J Mol Sci;2024 (Jul 20);25(14)

Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID). Besides ASD and ID and other symptoms, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1(B55), represent excellent models for research in the FXS field. During this study, sleep patterns and CR in dFMR1(B55) mutants were analyzed, using a new platform based on continuous high-resolution videography integrated with a highly-customized version of an open-source software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1(B55) male mutants sleep more and can be considered weak rhythmic flies rather than totally arrhythmic and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of affordable videography and software used in the current study is a significant improvement over previous methods and will enable broader adaptation of such high-resolution behavior monitoring methods.

Lien vers le texte intégral (Open Access ou abonnement)

29. Mingins JE, Tarver J, Pearson E, Edwards G, Bird M, Crawford H, Oliver C, Shelley L, Waite J. Development and psychometric properties of the Clinical Anxiety Scale for People with Intellectual Disabilities (ClASP-ID). J Neurodev Disord;2024 (Jul 27);16(1):43.

BACKGROUND: There is a critical need for the development of dependable and valid anxiety assessment tools suitable for people with moderate to severe intellectual disabilities, particularly those who speak few or no words. Distinguishing anxiety from distress caused by physical discomfort (pain) or characteristics associated with autism, prevalent in this population, necessitates specialised assessment tools. This study (a) developed a parent-report anxiety questionnaire tailored for individuals with severe to moderate intellectual disabilities, potentially with a co-diagnosis of autism, and (b) evaluated the psychometric attributes of this novel measure. METHODS: A comprehensive approach involving literature reviews, inspection of existing tools, and interviews with clinicians and parents guided the creation of the Clinical Anxiety Scale for People with Intellectual Disabilities. The tool was completed by parents or caregivers (N = 311) reporting on individuals aged 4 or older with intellectual disabilities. RESULTS: Exploratory factor analysis indicated a four-factor structure encompassing anxiety, pain, low energy/withdrawal, and consolability. The anxiety factor explained the most variance in scores (26.3%). The anxiety, pain, low energy/withdrawal subscales demonstrated robust internal consistency (α = 0.81-0.92), and convergent, divergent, and discriminant validity. Robustness of these subscales was further evidenced by test-retest reliability (ICC = 0.79-0.88) and inter-rater reliability (ICC = 0.64-0.71). Subgroup analyses consistently demonstrated strong psychometric properties among individuals diagnosed with non-syndromic autism (N = 98), children (N = 135), adults (N = 175), and across diverse communication abilities within the sample. Moreover, individuals diagnosed with both autism and anxiety exhibited significantly higher scores on the anxiety subscale compared to those without an anxiety diagnosis, while showing no difference in autism characteristic scores. CONCLUSIONS: The findings indicate that the Clinical Anxiety Scale for People with Intellectual Disabilities is a promising measure for use across diverse diagnostic groups, varying communication abilities, and with people with moderate to severe intellectual disabilities.

Lien vers le texte intégral (Open Access ou abonnement)

30. Mok KM, Sze CHH, Yu CCW, Mak E, Chan DFY, Wong SWL. A Self-Narrative Study: Changes in Physical Ability and Social Communication in Children with Autism through Taekwondo Training with Elements of Music Therapy from the Parents’ Perspective. Behav Sci (Basel);2024 (Jun 25);14(7)

Autism spectrum disorder (ASD) significantly affects social and motor skills development in early, middle or even late childhood. To promote social and motor skills development among autistic children, an intervention consisting of Taekwondo and elements of music therapy was designed and implemented in Hong Kong. The objective of the current study is to investigate the effectiveness of this training, based on parents’ observations of their children who had completed the key stage of the training. Thirteen parents or caregivers (n = 13) whose children with autism participated in our Taekwondo training for two months were interviewed. Three major themes were identified by thematic analysis: (A) social skills-related change after the intervention, (B) motor skills-related change after the intervention, (C) characteristics of the intervention (i.e., session arrangement, tutor/coach attitude). Our findings show that our training was perceived by parents to have a significant impact on the promotion of physical ability and social communication in autistic children.

Lien vers le texte intégral (Open Access ou abonnement)

31. Moschetti A, Giangreco M, Ronfani L, Cervellera S, Ruffilli MP, Nume C, Barbi E, Servidio AG. An ecological study shows increased prevalence of autism spectrum disorder in children living in a heavily polluted area. Sci Rep;2024 (Jul 26);14(1):17159.

The burden of autism spectrum disorder (ASD) is increasing worldwide with genetic, epigenetic, and environmental factors being possibly responsible for the observed epidemiological figures. In the setting of environmental exposure, the city of Taranto, in Southern Italy, represents an interesting case study as it hosts well inside the city one of the biggest steel plants in Europe. This is a cross-sectional ecological study carried out in the year 2020 in the province of Taranto designed to estimate the burden of ASD in the municipalities of Taranto and Statte, classified as high environmental risk areas (Contaminated Site of National Interest-SIN), compared to the other 27 municipalities of the same province. Differences have been evaluated using the Chi Square Test. Children aged 6-11 years identified in SIN municipalities had a statistically significant higher prevalence of ASD than children of other municipalities (9.58 vs. 6.66/1000 respectively, p = 0.002). No statistically significant difference was observed for the 12-18 years group (3.41 vs. 2.54/1000, p = 0.12). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

Lien vers le texte intégral (Open Access ou abonnement)

32. Nayar K, Landau E, Martin GE, Stevens CJ, Xing J, Sophia P, Guilfoyle J, Gordon PC, Losh M. Narrative Ability in Autism and First-Degree Relatives. J Autism Dev Disord;2024 (Jul 26)

Narrative is an important communication skill for sharing personal experiences and connecting with others. Narrative skills are often impacted in autism spectrum disorder (ASD) and have important consequences for social interactions and relationships. Subtle differences in narrative have also been reported among first-degree relatives of autistic individuals, suggesting that narrative may also be an etiologically important language-related skill that is influenced by genes associated with ASD. This study examined narrative ability and related visual attention during narration in ASD and first-degree relatives of individuals with ASD (siblings and parents) to understand how narrative and related attentional styles may be variably impacted across the spectrum of ASD genetic influence. Participants included 56 autistic individuals, 42 siblings of autistic individuals, 49 controls, 161 parents of autistic individuals, and 61 parent controls. Narratives were elicited using a wordless picture book presented on an eye tracker to record concurrent gaze. Findings revealed parallel patterns of narrative differences among ASD and sibling groups in the use of causal language to connect story elements and the use of cognitive and affective language. More subtle differences within the domain of causal language were evident in ASD parents. Parallel patterns in the ASD and sibling groups were also found for gaze during narration. Findings implicate causal language as a critical narrative skill that is impacted in ASD and may be reflective of ASD genetic influence in relatives. Gaze patterns during narration suggest similar attentional mechanisms associated with narrative among ASD families.

Lien vers le texte intégral (Open Access ou abonnement)

33. Parenti M, Slupsky CM. Disrupted Prenatal Metabolism May Explain the Etiology of Suboptimal Neurodevelopment: A Focus on Phthalates and Micronutrients and their Relationship to Autism Spectrum Disorder. Adv Nutr;2024 (Jul 24):100279.

Pregnancy is a time of high metabolic coordination, as maternal metabolism adapts to support the growing fetus. Many of these changes are coordinated by the placenta, a critical fetal endocrine organ and the site of maternal-fetal crosstalk. Dysregulation in maternal and placental metabolism during pregnancy has been linked to adverse outcomes, including altered neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to metabolic alterations in both children and their mothers. Prenatal environmental exposures have been linked to risk of ASD through dysregulated maternal, placental, and fetal metabolism. In this review, we focus on recent studies investigating the associations between prenatal metabolism in the maternal-placental-fetal unit and the impact of prenatal environmental exposures to phthalates and micronutrients on ASD risk. By identifying the mechanisms through which phthalates and other ubiquitous endocrine disrupting chemicals influence development, and how nutritional interventions can impact those mechanisms, we can identify promising ways to prevent suboptimal neurodevelopment.

Lien vers le texte intégral (Open Access ou abonnement)

34. Putnam OC, McFayden TC, Harrop C. Sex Differences and Parent-Teacher Discrepancies in Reports of Autism Traits: Evidence for Camouflaging in a School Setting. J Autism Dev Disord;2024 (Jul 27)

The purpose of this study was to examine sex differences and informant discrepancies in parent- and teacher-reports of autism traits. Data were drawn from the Simons Simplex Collection to create a sex-matched sample of autistic youth (N = 388; 4-17 years). Included participants had both parent and teacher reports of autistic traits from the Social Responsiveness Scale (SRS). Within each sex group, parent and teacher raw SRS scores were compared. Scores within each informant group (parent/teacher) was assessed for sex differences. Predictors of parent-teacher discrepancies were examined. Despite no sex differences in parent-reported autistic traits, teachers reported males as having more autistic traits compared to females. Parents of females reported significantly more autistic traits than teachers across multiple domains. Being older and female were significant predictors of increased parent-teacher discrepancy for multiple domains. These results suggest discrepancies between the observed autistic traits for females at home and school and builds on the growing body of literature highlighting potential camouflaging across development in autistic youth: parent-teacher discrepancies may reflect ways that autistic females are overlooked by teachers due to conscious changes in behavior or gender-based expectations of female characteristics. Discussion of discrepancies on an individual basis may therefore alleviate potential long-term consequences of camouflaging.

Lien vers le texte intégral (Open Access ou abonnement)

35. Raman N, Ringold SM, Jayashankar A, Butera CD, Kilroy E, Harrison L, Cermak SA, Aziz-Zadeh L. Correction: Raman et al. Relationships between Affect Recognition, Empathy, Alexithymia, and Co-Occurring Conditions in Autism. Brain Sci. 2023, 13, 1161. Brain Sci;2024 (Jul 3);14(7)

In the original publication […].

Lien vers le texte intégral (Open Access ou abonnement)

36. Ricarte M, Tagkalidou N, Bellot M, Bedrossiantz J, Prats E, Gomez-Canela C, Garcia-Reyero N, Raldúa D. Short- and Long-Term Neurobehavioral Effects of Developmental Exposure to Valproic Acid in Zebrafish. Int J Mol Sci;2024 (Jul 13);25(14)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research.

Lien vers le texte intégral (Open Access ou abonnement)

37. Rizzo A, Sorrenti L, Commendatore M, Mautone A, Caparello C, Maggio MG, Özaslan A, Karaman H, Yıldırım M, Filippello P. Caregivers of Children with Autism Spectrum Disorders: The Role of Guilt Sensitivity and Support. J Clin Med;2024 (Jul 20);13(14)

Background/Objectives: Burden Syndrome, also known as Caregiver Syndrome, particularly affects those who serve in the role of informal caregiver in the presence of family members with conditions. The ABCX dual model examines the impact on the caregiver of the diagnosis of autism spectrum disorder (ASD) on the family. This model considers the severity of the stressor (A), the additional demands of life stress (aA), the family’s internal resources (B), the family’s external resources (bB), the family’s assessment of the situation (C), coping strategies (cC), and outcome (X). The purpose of the present study is to investigate the relationships between resilience, guilt, and burden of care in caregivers of children with ASD. Methods: Various assessment instruments were used, including the « Caregiver Burden Inventory » to measure burden, the « Brief Resilience Scale » to assess resilience, the « Guilt Sensitivity Questionnaire » to examine guilt sensitivity, and the « DA.L.I.A. » to collect information on parent and child characteristics. A total of 80 parents/caregivers participated in the research, including 53 women (Age M = 41.72; SD = 7.8) and 27 men (Age M = 43.35; SD = 6.29). Results: The findings indicate that individuals’ resilience to stressful events correlates negatively with burden, a developmental subtype. However, guilt seems not to play a significant role in the overall perception of burden. In contrast, it was found that the use of informal supports is associated with higher levels of guilt and emotional burden, whereas the use of formal supports is correlated with higher emotional burden, but not higher perceptions of guilt. Conclusions: This study provides important information about the support needed by caregivers and suggests how to address emotional burdens to prevent burnout and support families with children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

38. Salemi M, Schillaci FA, Lanza G, Marchese G, Salluzzo MG, Cordella A, Caniglia S, Bruccheri MG, Truda A, Greco D, Ferri R, Romano C. Transcriptome Study in Sicilian Patients with Autism Spectrum Disorder. Biomedicines;2024 (Jun 25);12(7)

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds. A total of 733 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with ASD, namely the GO Biological Process term « Response to Oxygen-Containing Compound ». Additionally, the GO Cellular Component pathway « Mitochondrion » stood out among other pathways, with differentially expressed genes predominantly affiliated with this specific pathway, implicating the involvement of different mitochondrial functions in ASD. Among the differentially expressed genes, FPR2 was particularly highlighted, belonging to three GO pathways. FPR2 can modulate pro-inflammatory responses, with its intracellular cascades triggering the activation of several kinases, thus suggesting its potential utility as a biomarker of pro-inflammatory processes in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

39. Shayestehfar M, Nakhostin-Ansari A, Jahandideh P, Memari S, Geoffrey Louie WY, Memari A. Pivotal response treatment and applied behavior analysis interventions for autism spectrum disorder delivered by human vs robotic agents: a systematic review of literature. Disabil Rehabil Assist Technol;2024 (Jul 27):1-12.

Robotic technology-aided instruction and interventions have been designed to support both Applied Behavior Analysis (ABA) and Pivotal Response Treatment (PRT) interventions for children with ASD. However, to the best of our knowledge, this field has not been systematically reviewed. Thus, we aimed to systematically review the literature to determine whether ABA or PRT methods in a robotic therapeutic context yield better outcomes for individuals with ASD, specifically in terms of approaching and accepting robots. A comprehensive search of electronic databases including PubMed, EMBASE, and Google Scholar was conducted. Randomized control trials (RCT) and pre-post-test design investigations that assessed the impact of ABA vs. PRT approach via robot-mediated technology vs. human trainers on intervention outcomes of children with ASD were selected and included in this systematic review. Finally, 13 papers met the criteria for inclusion in the systematic review. Two independent reviewers extracted the associated data from each selected study according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using the Cochrane Back Review Scale and JBI tool for quasi-experimental studies. We categorized two general classifications of findings including ABA vs. PRT as well as robotic technology vs. human. In conclusion, the existing investigations on the effect of robotic assistive technology using ABA or PRT approach are promising particularly in therapeutic contexts with a more natural context and social flavor. Assistive robotic technology could teach social skills with both Applied Behavior Analysis (ABA) and Pivotal Response Treatment (PRT) approach to children with Autism Spectrum Disorders (ASD) with an acceptable efficiency and efficacy as human delivered therapies.The use of robotic technology as a means of delivering ABA or PRT interventions could offer a valuable alternative approach to human trainers in the treatment of children with ASD, potentially enhancing their acceptance and engagement with therapy. eng

Lien vers le texte intégral (Open Access ou abonnement)

40. Singh J, Wilkins G, Goodman-Vincent E, Chishti S, Bonilla Guerrero R, McFadden L, Zahavi Z, Santosh P. Co-Occurring Methylenetetrahydrofolate Reductase (MTHFR) rs1801133 and rs1801131 Genotypes as Associative Genetic Modifiers of Clinical Severity in Rett Syndrome. Brain Sci;2024 (Jun 21);14(7)

AIM: Remethylation disorders such as 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency reduce the remethylation of homocysteine to methionine. The resulting hyperhomocysteinemia can lead to serious neurological consequences and multisystem toxicity. The role of MTHFR genotypes has not been investigated in patients with Rett Syndrome (RTT). In this study, we sought to assess the impact of co-occurring MTHFR genotypes on symptom profiles in RTT. METHOD: Using pharmacogenomic (PGx) testing, the MTHFR genetic polymorphisms rs1801133 (c.665C>T mutation) and rs1801131 (c.1286A>C mutation) were determined in 65 patients (18.7 years ± 12.1 [mean ± standard deviation]) with RTT as part of routine clinical care within the Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, a National and Specialist Child and Adolescent Mental Health Service (CAMHS) in the UK. The clinical severity of patients was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI). RESULTS: The clinical severity symptom distribution varied between the homozygous and heterozygous MTHFR rs1801133 and rs1801131 genotypes. Those with the homozygous genotype had a narrower spread of severity scores across several domains (language and communication, ambulation, hand-use and eye contact clinical domains). Patients with the homozygous genotype had statistically significantly greater CGI-Severity scores than individuals with a non-homozygous MTHFR genotype (Z = -2.44, p = 0.015). When comparing the ratings of moderately impaired (4), markedly impaired (5), severely impaired (6) and extremely impaired (7), individuals with the homozygous MTHFR genotype were more impaired than those with the non-homozygous MTHFR genotype (Z = -2.06, p = 0.039). There was no statistically significant difference in the number of prescribed anti-epileptic drugs between the genotypes. CONCLUSIONS: Our findings show that in those with a pathogenic RTT genetic variant, co-occurring homozygotic MTHFR rs1801133 and rs1801131 polymorphisms may act as associative genetic modifiers of clinical severity in a subset of patients. Profiling of rs1801133 and rs1801131 in RTT may therefore be useful, especially for high-risk patients who may be at the most risk from symptom deterioration.

Lien vers le texte intégral (Open Access ou abonnement)

41. Sobhani A, InanlooRahatloo K. Transcriptomic Analysis Reveals Sex-Based Differences in The Prefrontal Cortex of Autism Spectrum Disorder Patients. Cell J;2024 (Jul 13);26(5):320-328.

OBJECTIVE: The prevalence of neurological disorders often varies by sex, with conditions such as Alzheimer’s disease and autism spectrum disorder (ASD) demonstrating notable differences in incidence. The aim of this study is to understand the molecular basis for these divergences in order to facilitate the creation of sex-specific therapeutic strategies. MATERIALS AND METHODS: This study is a bioinformatic analysis of publicly available RNA sequencing datasets involving autism patients. The study utilized RNA sequencing data from postmortem human brains’ prefrontal cortex, including 38 neurotypical controls and 34 individuals with ASD. The sequencing data was obtained from previously published papers, and we downloaded the raw data from SRA. We investigated the molecular basis of sex-biased presentation in ASD through comprehensive transcriptomic analysis. RESULTS: Comparative analysis of gene expression between male and female subjects, both autistic and unaffected, was conducted, using a significance level of ≤0.01. In autistic individuals, 136 genes demonstrated differential expression between sexes, predominantly upregulated in males, indicating a bias in male gene expression. Among these, 12 genes were identified as risk factors in the SFARI dataset. While most sex-biased genes were autosomal, expression differences on sex chromosomes were also observed in neurotypical subjects. Notable genes included TCF7L2, collagen family genes, and solute carrier family genes. In ASD males, extracellular matrix (ECM) organization emerged as a significant pathway, while immune-related processes were prominent in unaffected individuals. CONCLUSION: Our study highlights the impact of the ECM pathway in ASD, with notable differences between sexes, particularly in males. MIR424 shows promise as a potential biomarker for ASD in males. Recognizing the importance of sex differences in ASD transcriptomic research is crucial, as these variances provide insights into the disorder’s pathophysiology and may guide the development of more personalized treatments for both sexes.

Lien vers le texte intégral (Open Access ou abonnement)

42. Steinhausen HC, Villumsen MD, Støving RK, Bilenberg N. Complete Spectrum of Physical Comorbidities with Autism Spectrum Disorder in a Nationwide Cohort. J Autism Dev Disord;2024 (Jul 27)

The associations between autism spectrum disorder (ASD) and physical diseases (PD) based on ICD-8 and ICD-10 diagnoses were studied, comparing with the risks of the general population. All individuals diagnosed before 30th April 2018 with ASD (n = 12,063) and a 5% random sample of the general population (n = 41,251) were drawn from Danish registers of the birth cohorts 1984-1995. For each of the entire spectrum of 13 PD categories, participants were followed from birth to first diagnosis, death, emigration, or 31st December 2017, whichever came first. Time from inclusion at birth to time of first physical diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. When compared to the control sample, the individuals with ASD had a substantial added immediate risk in infancy and in childhood for 12 of the 13 categories. Particularly prominent were estimated associations for nervous system diseases at ages 0-9, and diseases of the eye and adnexa at ages 0-11. The associations were observed for both sexes, but were stronger among females than males, especially for genitourinary system diseases. On the cumulative scale, individuals with ASD were at pronounced greater risk through follow-up for 8 categories, with the greatest cumulative risk of respiratory system diseases, which at ages 5 and 30 was 24.9% and 41.5% for the ASD cohort while for the control sample it was 16.3% and 34.5% at the same ages. Especially in infancy and childhood, the present study found increased risks for a multitude of physical diseases.

Lien vers le texte intégral (Open Access ou abonnement)

43. Thomas SD, Abdalla S, Eissa N, Akour A, Jha NK, Ojha S, Sadek B. Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer’s Disease, Parkinson’s Disease, and Autism Spectrum Disorder. Pharmaceuticals (Basel);2024 (Jun 25);17(7)

Histamine performs dual roles as an immune regulator and a neurotransmitter in the mammalian brain. The histaminergic system plays a vital role in the regulation of wakefulness, cognition, neuroinflammation, and neurogenesis that are substantially disrupted in various neurodegenerative and neurodevelopmental disorders. Histamine H3 receptor (H3R) antagonists and inverse agonists potentiate the endogenous release of brain histamine and have been shown to enhance cognitive abilities in animal models of several brain disorders. Microglial activation and subsequent neuroinflammation are implicated in impacting embryonic and adult neurogenesis, contributing to the development of Alzheimer’s disease (AD), Parkinson’s disease (PD), and autism spectrum disorder (ASD). Acknowledging the importance of microglia in both neuroinflammation and neurodevelopment, as well as their regulation by histamine, offers an intriguing therapeutic target for these disorders. The inhibition of brain H3Rs has been found to facilitate a shift from a proinflammatory M1 state to an anti-inflammatory M2 state, leading to a reduction in the activity of microglial cells. Also, pharmacological studies have demonstrated that H3R antagonists showed positive effects by reducing the proinflammatory biomarkers, suggesting their potential role in simultaneously modulating crucial brain neurotransmissions and signaling cascades such as the PI3K/AKT/GSK-3β pathway. In this review, we highlight the potential therapeutic role of the H3R antagonists in addressing the pathology and cognitive decline in brain disorders, e.g., AD, PD, and ASD, with an inflammatory component.

Lien vers le texte intégral (Open Access ou abonnement)

44. Uğurlu M, Sözer Boz E, Turgut S. Psychometric Properties of the Child Behavior Checklist (CBCL) for Ages 6-18 to Identify Autism Spectrum Disorders (ASD) in a Turkish Parent Sample. J Autism Dev Disord;2024 (Jul 26)

The Child Behavior Checklist for ages 6-18 (CBCL/6-18) is broadly used for psycho-educational assessment in identifying children’s behavior problems in special education and psychology. However, the usefulness of the CBCL/6-18 in a Turkish sample still needs to be investigated. The current study aimed to investigate the psychometric properties of the measures of the CBCL/6-18 within a sample of Turkish parents. The psychometric evaluation includes item calibration using the Partial Credit Model (PCM). We analyzed data from 548 parents who have children with autism spectrum disorder. According to the PCM calibration, the results suggested that the Internalizing, Externalizing, and Total Problem subscales were unidimensional and showed local independence successfully. All subscales demonstrated adequate reliability, indicating that the scale distinguishes between children with different behavior problems. The subscales had varying item step ordering, meaning that transitions from one category to second by parent ratings are relatively straightforward. Some items with easy-to-define behavior problems, for example, Item 42 (constipated), were more likely to be endorsed by parents. Consequently, the CBCL/6-18 has adequate psychometric properties for accurately assessing problem behaviors in children based on parent ratings.

Lien vers le texte intégral (Open Access ou abonnement)

45. van de Meent I, Koomen L, de Boer R, Le Clercq L, Janssen D, Boute M, Maat A, van Dellen E, Cahn W. Forward head posture associated with reduced cardiorespiratory fitness in psychotic disorders compared to autism spectrum disorder and healthy controls. Sci Rep;2024 (Jul 26);14(1):17143.

Individuals with psychotic disorders often lead sedentary lives, heightening the risk of developing forward head posture. Forward head posture affects upper cervical vertebrae, raising the likelihood of daily discomforts like skeletal misalignment, neck pain, and reduced cardiorespiratory fitness. Improving cardiorespiratory fitness in psychotic disorders is relevant, given its proven benefits in enhancing physical and mental health. This study investigates forward head posture by measuring craniovertebral angles in psychotic disorders and the relationship with reduced cardiorespiratory fitness. To determine whether forward head posture is specific to psychotic disorders, we also included individuals with autism spectrum disorder and healthy controls. Among 85 participants (32 psychotic disorders, 26 autism spectrum disorder, 27 healthy controls), photogrammetric quantification revealed a significantly lower mean craniocervical angle in psychotic disorders compared to autism spectrum disorder (p =  < 0.02) and the healthy control group (p =  < 0.01). Reduced craniovertebral angle is related to diminished cardiorespiratory fitness in psychosis (R(2) = 0.45, p =  < 0.01) but not in other control groups. This study found reduced craniovertebral angles, indicating forward head posture in psychotic disorders. Moreover, this relates to diminished cardiorespiratory fitness. Further research is needed to examine the underlying causes and to investigate whether this can be reversed through physical therapy.

Lien vers le texte intégral (Open Access ou abonnement)

46. Varga A, Kedves R, Sághy K, Garab D, Zádor F, Lendvai B, Lévay G, Román V. R-Baclofen Treatment Corrects Autistic-like Behavioral Deficits in the RjIbm(m):FH Fawn-Hooded Rat Strain. Pharmaceuticals (Basel);2024 (Jul 13);17(7)

The Fawn-hooded rat has long been used as a model for various peripheral and central disorders and the data available indicate that the social behavior of this strain may be compromised. However, a thorough description of the Fawn-hooded rat is unavailable in this regard. The objective of the present study was to investigate various aspects of the Fawn-hooded rat’s social behavior in depth. Our results show that several facets of socio-communicational behavior are impaired in the RjIbm(m):FH strain, including defective ultrasonic vocalizations in pups upon maternal deprivation, reduced social play in adolescence and impaired social novelty discrimination in adulthood. In addition, Fawn-hooded rats exhibited heightened tactile sensitivity and hyperactivity. The defects observed were comparable to those induced by prenatal valproate exposure, a widely utilized model of autism spectrum disorder. Further on, the pro-social drug R-baclofen (0.25-1 mg/kg) reversed the autistic-like defects observed in Fawn-hooded rats, specifically the deficiency in ultrasonic vocalization, tactile sensitivity and social novelty discrimination endpoints. In conclusion, the asocial, hypersensitive and hyperactive phenotype as well as the responsivity to R-baclofen indicate this variant of the Fawn-hooded rat strain may serve as a model of autism spectrum disorder and could be useful in the identification of novel drug candidates.

Lien vers le texte intégral (Open Access ou abonnement)

47. Zafirovski K, Aleksoska MT, Thomas J, Hanna F. Impact of Gluten-Free and Casein-Free Diet on Behavioural Outcomes and Quality of Life of Autistic Children and Adolescents: A Scoping Review. Children (Basel);2024 (Jul 16);11(7)

BACKGROUND: Gluten- and casein-containing foods could aggravate the symptoms of children and adolescents with autism spectrum disorder (ASD), and subsequently impact their quality of life. However, there is a mixed opinion among researchers concerning the impact of alternative diet on reducing ASD symptoms. OBJECTIVE: This scoping review aimed at examining the impact of the « gluten-free, casein-free » (GFCF) diet on health outcomes and the quality of life among autistic children and adolescents. METHODS: A scoping review of the literature was performed following the Joanna Briggs Institute (JBI) guidelines. Four databases, including EbscoHost, Medline, CINAHL, and ProQuest, were used to obtain subject-specific studies relevant to the research question and published between July 2013 and March 2024. A comprehensive search using keywords such as « autism spectrum disorder », « gluten-free diet », and « casein-free diet » was conducted to obtain articles related to the research focus area. Only full-text, peer-reviewed, written in English articles were selected. Data extraction and data analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension to Scoping Review (PRISMA-ScR) protocol. RESULTS: From the initial 586 studies, a total of 27 articles were included in the final analysis of the review. The thematic analysis included « GFCF diet and improvement of the core autistic symptoms », « the gut-brain link », « dietary interventions and autism », « possible side effects due to the GCFC diet », and « inconclusive studies and mixed opinions ». A majority of the studies showed a positive effect of the GFCF diet on a variety of autistic symptoms, including positive changes in cognitive skills, behaviour, and gastrointestinal symptoms, while some showed conflicting evidence. CONCLUSIONS: The currently available evidence on the impact of the « GFCF » diet on the quality of life of autistic children and adolescents may warrant potentially effective interventions for alleviating symptoms of autism spectrum disorders. However, this scoping review highlights the need for more research to provide more reliable evidence on the health outcomes and quality of life of ASD sufferers to guide practice.

Lien vers le texte intégral (Open Access ou abonnement)

48. Zhuang S, Bougoure M, Leong DJ, Dean L, Reddrop S, Naragon-Gainey K, Maybery M, Tan DW, Magiati I. Examining an integrated path model of psychological and sociocultural predictors of camouflaging in autistic adults. Autism;2024 (Jul 27):13623613241262110.

Many autistic people use strategies known as ‘camouflaging’ to change how noticeable their autistic traits are in social situations. Previous research suggests that camouflaging is largely motivated by psychological and social factors. However, most studies so far have only looked at a few psychosocial factors related to camouflaging. In this study, we explored a model that included several individual psychological factors (such as fear of being negatively judged, self-esteem and autistic identity) and broader social and cultural factors (such as perceived stigma, negative life events, cultural emphasis on conformity and desire to fit in or stand out). We surveyed 225 autistic adults aged 18-77 years online. Our findings showed that several sociocultural factors were indirectly linked to camouflaging through individual psychological factors. Fear of being negatively judged emerged as a strong predictor of camouflaging. Specifically, autistic adults who perceived greater stigma, felt greater pressure to conform, had a lesser desire to stand out and a greater desire to fit in tended to experience a greater fear of being negatively judged and reported more camouflaging. In addition, those who experienced more negative life events were more likely to engage in camouflaging. Our study identifies key psychological and social factors as potential targets for social change. Our findings emphasise that our societies need to shift away from stigmatising attitudes towards accepting and including autistic people, which could reduce the pressure on autistic individuals to camouflage in social situations.

Lien vers le texte intégral (Open Access ou abonnement)