1. Afsharnejad B, Black MH, Falkmer M, Bölte S, Girdler S. The Methodological Quality and Intervention Fidelity of Randomised Controlled Trials Evaluating Social Skills Group Programs in Autistic Adolescents: A Systematic Review and Meta-analysis. Journal of autism and developmental disorders. 2023.

A systematic review and meta-analysis were utilised to explore the methodological quality, program fidelity, and efficacy of social skills group programs (SSGPs) aiming to support autistic adolescents in navigating their everyday social worlds. The study evaluated the methodological quality and theoretical fidelity of studies, with a random effect meta-analysis conducted to summarise the overall efficacy of SSGP and its effect on social communication and interaction, behavioural/emotional challenges, adaptive functioning, and autism characteristics. Although findings from the 18 identified studies indicated an adjusted medium overall effect with these programs successfully supporting autistic adolescents’ socialisation needs (g = 0. 60, p < 0.001), most studies demonstrated medium to low program fidelity despite their good methodological quality. Given the significant heterogeneity of SSGPs and variations in the design and measurement frameworks of efficacy studies, understanding the generalisability of the findings of this research is unclear.

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2. Alhuzimi TE, Alharbi MH. Perceptions of Parents on Management of Food Allergy in Children with Autism Spectrum Disorder (ASD) in Saudi Arabia. Children (Basel, Switzerland). 2022; 10(1).

BACKGROUND: Food allergy is one of the most serious health concerns spread across the globe. Its awareness and management are undervalued, especially in children with autism spectrum disorders (ASD). The aim of this study is to explore the perception of parents of autistic children from Saudi Arabia on the prevalence, knowledge, awareness and management of food allergens. METHODS: A cross-sectional exploratory self-administrated online survey was conducted in Saudi Arabia, where 125 parents of autistic children voluntarily took part in the survey from April to August 2022. RESULTS: This study indicates that less than one-fourth of autistic children suffering from food allergies, while most of them are allergic to proteins mainly. Examination of the knowledge level of these parents regarding food allergies, depending upon the score of correct answers given by them, showed that a majority of parents had a moderate level of knowledge on food allergy. Even though there was awareness about food allergens, the use of medical interventions was not employed much. However, the parents were mindful of food labeling and found it to be useful in avoiding known food allergies. Mediating effects of food allergy were observed in the relationship between food allergy knowledge and its management. Moreover, the source of information about food allergies was also found to be significantly associated with the knowledge score and the level of awareness regarding food allergies. This study provides evidence that there is a significant influence of food allergy knowledge of parents of autistic children on its management among autistic children from Saudi Arabia, with awareness of food allergies as the mediator. CONCLUSIONS: This is the first study where the prevalence, knowledge and management, along with awareness of food allergy, has been empirically explored through the perception of parents of autistic children.

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3. Alsubaiei SRM, Alfawaz HA, Almubarak AY, Alabdali NA, Ben Bacha A, El-Ansary A. Independent and Combined Effects of Probiotics and Prebiotics as Supplements or Food-Rich Diets on a Propionic-Acid-Induced Rodent Model of Autism Spectrum Disorder. Metabolites. 2022; 13(1).

The link between nutrition and autism spectrum disorder (ASD) as a neurodevelopmental condition, which is clinically presented as significant delays or deviations in interaction and communication, has provided a fresh point of view and signals that nutrition may play a role in the etiology of ASD, as well as playing an effective role in treatment by improving symptoms. In this study, 36 male albino rat pups were used. They were randomly divided into five groups. The control group was fed only a standard diet and water for the 30 days of the experiment. The second group, which served as a propionic acid (PPA)-induced rodent model of ASD, received orally administered PPA (250 mg/kg body weight (BW)) for 3 days, followed by feeding with a standard diet until the end of the experiment. The three other groups were given PPA (250 mg/kg body weight (BW)) for 3 days and then fed a standard diet and orally administered yogurt (3 mL/kg BW/day), artichokes (400 mL/kg BW/day), and a combination of Lacticaseibacillus rhamnosus GG at 0.2 mL daily (1 × 10(9) CFU; as the probiotic of yogurt) and luteolin (50 mg/kg BW/day; as the major antioxidant and anti-inflammatory ingredient of artichokes) for 27 days. Biochemical markers, including gamma-aminobutyric acid (GABA), reduced glutathione (GSH), glutathione peroxidase (GPx1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured in brain homogenates in all groups. The data showed that while PPA demonstrated oxidative stress and neuroinflammation in the treated rats, yogurt, Lacticaseibacillus rhamnosus GG as a probiotic, and luteolin as a prebiotic ingredient in artichokes were effective in alleviating the biochemical features of ASD. In conclusion, nutritional supplementation seems to be a promising intervention strategy for ASD. A combined dietary approach using pro- and prebiotics resulted in significant amelioration of most of the measured variables, suggesting that multiple interventions might be more relevant for the improvement of biochemical autistic features, as well as psychological traits. Prospective controlled trials are needed before recommendations can be made regarding the ideal ASD diet.

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4. da Silva ACF, Barbosa TS, Gavião MBD. Parental Perception of the Oral Health-Related Quality of Life of Children and Adolescents with Autism Spectrum Disorder (ASD). International journal of environmental research and public health. 2023; 20(2).

This study evaluated the parental perception of the oral health-related quality of life (OHRQoL) of children and adolescents with autism spectrum disorder (ASD) and their family functioning. Moreover, sociodemographic factors associated with parental ratings of OHRQoL were assessed. A hundred parents/guardians of children and adolescents aged 6 to 14 years with ASD (ASD group) and 101 unaffected children and adolescents (UCA group) participated. Data collection was carried out using a Google form, containing three sections: (1st) Socioeconomic data and health history; (2nd) Oral health assessment by parental report; (3rd) The short forms of the Parental-Caregiver Perceptions Questionnaire (16-P-CPQ) and the Family Impact Scale (4-FIS). The scores of 16-P-CPQ total and subscales and 4-FIS were significantly higher for the ASD group (p < 0.02), except for the oral symptoms subscale (p > 0.05). Older ages (OR = 1.24), brushing 0/1x day (OR = 2.21), teeth grinding (OR = 2.20), gingival bleeding (OR = 3.34), parents with an elementary school degree (OR = 0.314) and family incomes less or equal to the minimum wage (OR = 3.049) were associated with a worse OHRQoL. Parents in the ASD group had a worse perception of QHRQoL when compared to the UCA group. ‘Frequency of tooth brushing’, ‘gingival bleeding’, and ‘teeth grinding’ were predictors of the worst parental perception of their children’s OHRQoL. Families with low socioeconomic conditions were more strongly affected by the oral conditions of their children.

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5. Di Sarro R, Varrucciu N, Di Santantonio A, Natali F, Kaleci S, Bianco A, Cappai M, Lucchi F, Bertelli MO. Appropriateness of psychopharmacological therapies to psychiatric diagnoses in persons with autism spectrum disorder with or without intellectual disabilities: a cross-sectional analytic study. Expert opinion on drug safety. 2023.

BACKGROUND: Available observational studies have highlighted high rates of psychotropic medication in persons with Autistic Spectrum Disorder (ASD) with or without Intellectual Disability, which seems to be associated with the management of problem behaviors more than co-occurrent diagnoses of psychiatric disorders. The purpose of the study is to investigate psychopharmacology use and diagnoses of co-occurrent psychiatric disorder (PD) in a sample of persons with ASD attending a public mental health service in Emilia Romagna, Italy. METHODS: The present study is a multicenter, prospective cohort study. RESULTS: 275 persons out of 486 (56.5%) resulted to receive at least one psychotropic drug, compared to 74 persons (15.2%) that were diagnosed with a PD. 63.6% were on poly-pharmacotherapy (2-10 compounds), with 37.8% receiving 3 or more medications. Antipsychotics were the most frequently prescribed class of psychotropic drugs (89%), followed by antiepileptics/mood stabilizers/lithium (42.1%) and anxiolytics (BDZ) (38.5%). Most common psychiatric disorders were psychotic disorders (29.7%), followed by anxiety disorders (17.5%), bipolar disorders (12.2%), and depressive disorders (9.4%). CONCLUSIONS: Our findings support earlier research showing that many individuals with ASD receive pharmacotherapy without being diagnosed with a co-occurring psychiatric disorder, indicating that the main reasons for prescription and the type of compound frequently have little to no link with specific psychopathology.

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6. ElNakieb Y, Ali MT, Elnakib A, Shalaby A, Mahmoud A, Soliman A, Barnes GN, El-Baz A. Understanding the Role of Connectivity Dynamics of Resting-State Functional MRI in the Diagnosis of Autism Spectrum Disorder: A Comprehensive Study. Bioengineering (Basel, Switzerland). 2023; 10(1).

In addition to the standard observational assessment for autism spectrum disorder (ASD), recent advancements in neuroimaging and machine learning (ML) suggest a rapid and objective alternative using brain imaging. This work presents a pipelined framework, using functional magnetic resonance imaging (fMRI) that allows not only an accurate ASD diagnosis but also the identification of the brain regions contributing to the diagnosis decision. The proposed framework includes several processing stages: preprocessing, brain parcellation, feature representation, feature selection, and ML classification. For feature representation, the proposed framework uses both a conventional feature representation and a novel dynamic connectivity representation to assist in the accurate classification of an autistic individual. Based on a large publicly available dataset, this extensive research highlights different decisions along the proposed pipeline and their impact on diagnostic accuracy. A large publicly available dataset of 884 subjects from the Autism Brain Imaging Data Exchange I (ABIDE-I) initiative is used to validate our proposed framework, achieving a global balanced accuracy of 98.8% with five-fold cross-validation and proving the potential of the proposed feature representation. As a result of this comprehensive study, we achieve state-of-the-art accuracy, confirming the benefits of the proposed feature representation and feature engineering in extracting useful information as well as the potential benefits of utilizing ML and neuroimaging in the diagnosis and understanding of autism.

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7. Figuereo YF, Lewis J, Lee P, Walker SJ. Autism Spectrum Disorder in the Dominican Republic: A Mini Review of the Current Situation. Children (Basel, Switzerland). 2023; 10(1).

As the recognition of autism spectrum disorder (ASD) increases, and the prevalence estimates of ASD continue to rise throughout the world, it has become apparent that access to diagnostic and treatment services is highly dependent on geography. Even within countries such as the United States, which has received significant interest and investment in understanding, diagnosing, treating, and providing programs for those with ASD over the last 20+ years, access to information and services is uneven. In poorer countries such as the Dominican Republic (DR), where >40% of citizens live below the poverty level and access to quality healthcare overall continues to be a challenge, issues associated with ASD are not yet being adequately addressed. The objective of this review is to provide a realistic synopsis of the resources currently available to Dominicans who have a family member or loved one with ASD. We examine the challenges these families face in finding care, the stigma associated with ASD, and programs available for people with ASD. We conclude that while the DR is making progress in its efforts to address ASD, there is still much work to be done.

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8. Fucà E, Guerrera S, Valeri G, Casula L, Novello RL, Menghini D, Vicari S. Psychiatric Comorbidities in Children and Adolescents with High-Functioning Autism Spectrum Disorder: A Study on Prevalence, Distribution and Clinical Features in an Italian Sample. Journal of clinical medicine. 2023; 12(2).

This study investigated the prevalence and distribution of psychiatric comorbidities in a group of 472 children and adolescents with ASD aged 3-18 years. We examined differences in age, sex, IQ, adaptive skills, and ASD symptom severity by comparing participants with ASD (ASD group) with participants with ASD and a psychiatric disorder (ASD/PSY group). Overall, 32.2% of participants had a comorbid psychiatric condition. Attention deficit/hyperactivity disorder (ADHD) was the most frequent diagnosis among preschoolers (20.4%); among school-age children, ADHD and anxiety/obsessive-compulsive disorders were the most frequent conditions (21% and 10.6%, respectively); finally, adolescents exhibit higher prevalence of anxiety/obsessive-compulsive disorders (21.8%). The ASD/PSY group showed a higher percentage of males, they were older and showed lower adaptive skills than the group with ASD; moreover, their mothers exhibited higher stress levels than mothers of participants in the ASD group. The comparison between age groups in participants within ASD/PSY group revealed that preschoolers had lower IQ than school-age children and adolescents, and worse adaptive skills, more repetitive behaviors, and restricted interests than adolescents. This study highlights the importance of an accurate diagnosis of psychiatric comorbidities in children and adolescents with ASD, also considering individual and family impairment.

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9. Geng X, Fan X, Zhong Y, Casanova MF, Sokhadze EM, Li X, Kang J. Abnormalities of EEG Functional Connectivity and Effective Connectivity in Children with Autism Spectrum Disorder. Brain sciences. 2023; 13(1).

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that interferes with normal brain development. Brain connectivity may serve as a biomarker for ASD in this respect. This study enrolled a total of 179 children aged 3-10 years (90 typically developed (TD) and 89 with ASD). We used a weighted phase lag index and a directed transfer function to investigate the functional and effective connectivity in children with ASD and TD. Our findings indicated that patients with ASD had local hyper-connectivity of brain regions in functional connectivity and simultaneous significant decrease in effective connectivity across hemispheres. These connectivity abnormalities may help to find biomarkers of ASD.

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10. Hollestein V, Poelmans G, Forde NJ, Beckmann CF, Ecker C, Mann C, Schäfer T, Moessnang C, Baumeister S, Banaschewski T, Bourgeron T, Loth E, Dell’Acqua F, Murphy DGM, Puts NA, Tillmann J, Charman T, Jones EJH, Mason L, Ambrosino S, Holt R, Bölte S, Buitelaar JK, Naaijen J. Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure. Translational psychiatry. 2023; 13(1): 18.

The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.

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11. Horwitz E, Vos M, De Bildt A, Greaves-Lord K, Rommelse N, Schoevers R, Hartman C. Sex differences in the course of autistic and co-occurring psychopathological symptoms in adolescents with and without autism spectrum disorder. Autism : the international journal of research and practice. 2023: 13623613221146477.

There is an ongoing debate as to whether autism spectrum disorder (ASD) is expressed differently in women than men. Studies on sex differences in autistic symptoms and symptoms of other psychiatric problems present in individuals with autism generally do not include a general population comparison group, making it unclear whether differences are specific to autism or merely reflecting development in the general population. In this study, we compared sex differences in the course of autistic and at the same time present symptoms of other psychiatric problems in adolescents with milder forms of ASD to those in a group of the general population with an equal intelligence quotient (IQ) and socioeconomic status. Data of five assessment moments from ages 11 to 22 years were analyzed using a statistic procedure that allowed us to determine which factors affect the course of symptoms over time. We found that in adolescence, sex differences in the course of psychopathological symptoms specific for autism are confined to the repetitive stereotyped domains. Males had higher scores on the sensory/stereotypic and resistance to change domains, the latter difference disappeared during the course of adolescence due to an increase of these problems in autistic females. Other sex differences, among which an increase over time in mood and anxiety problems in females was the most outstanding, were also observed in females without autism. These sex-specific differences have relevance in the clinical care of autistic men and women, although they are subtle compared to differences between individuals with and without autism.

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12. Hosokawa R, Yoshino Y, Funahashi Y, Horiuchi F, Iga JI, Ueno SI. MiR-15b-5p Expression in the Peripheral Blood: A Potential Diagnostic Biomarker of Autism Spectrum Disorder. Brain sciences. 2022; 13(1).

BACKGROUND: Autism spectrum disorder (ASD), is a neurodevelopmental disorder that is known to have a high degree of heritability. Diagnosis of ASD is difficult because of the high heterogeneity of the clinical symptoms. MicroRNAs (miRNAs) can potentially be diagnostic biomarkers for ASD, and several studies have shown the relationship between miRNAs and ASD pathogenesis. In this study, we investigated ten miRNA and mRNA expression of target genes in peripheral blood to explore a diagnostic biomarker for ASD. METHODS: We recruited control and ASD subjects for the discovery cohort (n = 6, each) and replication cohort (n = 20, each). Using qPCR, miRNA and mRNA expression was measured using the SYBR green and probe methods, respectively. In-silico prediction was used for identifying target genes of miRNAs. An in vitro experiment using HEK293 cells was conducted to investigate whether miR-15b-5p modulates the predicted target genes (TGFBR3 and MYBL1). RESULTS: miR-15b-5p expression indicated an increased trend in the discovery cohort (p = 0.052) and a significant upregulation in the replication cohort (p = 0.021). In-silico analysis revealed that miR-15b-5p is relevant to cell development and Wnt signaling. The decreased trends of TGFBR3 and MYBL expression were the same as in previous RNA-seq data. MiR-15b-5p positively regulated TGFBR3 expression in in vitro experiments. CONCLUSIONS: Upregulated miR-15b-5p expression may represent a useful diagnostic marker of ASD subjects, and it may regulate TGFBR3 mRNA expression. These findings indicate a new perspective in the understanding of the pathogenesis of ASD.

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13. Huber JF, Loh A, Monga S, Esufali J, Shouldice M. Development of a Novel Multi-Disciplinary Specialized Care Service for Children and Adolescents with Autism Spectrum Disorder and/or Intellectual/Developmental Disability in a Tertiary Children’s Hospital Setting. Children (Basel, Switzerland). 2022; 10(1).

Children and adolescents with autism spectrum disorder (ASD) and/or Intellectual/Developmental Disability (IDD) are at greater risk of developing comorbid medical conditions, mental health diagnoses, behavioral challenges, and having overall poorer physical and mental health outcomes. Hospital environments present unique stressors and challenges for children and adolescents with ASD/IDD including a change in familiar environment, unpredictable routines, and exposure to sensory stimuli that may be overwhelming. While many school boards have specialized multi-disciplinary special needs support teams and services made up of professionals with expertise in supporting students with ASD/IDD, most hospitals do not have a formal multi-disciplinary ASD/IDD support team in place to support patients, families, and health care staff across the hospital. There is an emerging recognition of the need for specialized multi-disciplinary developmental-behavioral and mental health expertise in hospital inpatient settings. This paper describes the framework for the development of an innovative multi-disciplinary program to better support children and adolescents with ASD/IDD within a tertiary children’s hospital setting.

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14. Kang J, Fan X, Zhong Y, Casanova MF, Sokhadze EM, Li X, Niu Z, Geng X. Transcranial Direct Current Stimulation Modulates EEG Microstates in Low-Functioning Autism: A Pilot Study. Bioengineering (Basel, Switzerland). 2023; 10(1).

Autism spectrum disorder (ASD) is a heterogeneous disorder that affects several behavioral domains of neurodevelopment. Transcranial direct current stimulation (tDCS) is a new method that modulates motor and cognitive function and may have potential applications in ASD treatment. To identify its potential effects on ASD, differences in electroencephalogram (EEG) microstates were compared between children with typical development (n = 26) and those with ASD (n = 26). Furthermore, children with ASD were divided into a tDCS (experimental) and sham stimulation (control) group, and EEG microstates and Autism Behavior Checklist (ABC) scores before and after tDCS were compared. Microstates A, B, and D differed significantly between children with TD and those with ASD. In the experimental group, the scores of microstates A and C and ABC before tDCS differed from those after tDCS. Conversely, in the control group, neither the EEG microstates nor the ABC scores before the treatment period (sham stimulation) differed from those after the treatment period. This study indicates that tDCS may become a viable treatment for ASD.

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15. Kyvelidou A, DeVeney S, Katsavelis D. Development of Infant Sitting Postural Control in Three Groups of Infants at Various Risk Levels for Autism Spectrum Disorder. International journal of environmental research and public health. 2023; 20(2).

The purpose of this study was to examine the development of sitting postural control among two groups of infants at elevated risk for autism spectrum disorders (ASD) and a group of infants at typical risk for ASD and its association with cognitive, language and communication skills at a later age. We visited infants in their home environment from the onset of sitting until sitting independence and at 12 and 18 months of age. We collected data on sitting posture (center of pressure), through a portable force platform, as well as communication, cognitive and social behavior assessments at various time points. Our results showed that postural control differences at the onset of sitting, were present among the groups of infants but there were no statistically significant differences among the groups in the development of sitting posture. In addition, there were statistically significant communication differences among the groups and mostly the change in sample entropy in the anterior/posterior direction (posture measure) was significantly correlated with other skills at a later age. This study highlights the importance of investigating multiple at-risk groups to identify unique developmental pathways that may lead to an ASD diagnosis.

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16. Lee K, Mills Z, Cheung P, Cheyne JE, Montgomery JM. The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders. Pharmaceuticals (Basel, Switzerland). 2022; 16(1).

NMDA-type glutamate receptors are critical for synaptic plasticity in the central nervous system. Their unique properties and age-dependent arrangement of subunit types underpin their role as a coincidence detector of pre- and postsynaptic activity during brain development and maturation. NMDAR function is highly modulated by zinc, which is co-released with glutamate and concentrates in postsynaptic spines. Both NMDARs and zinc have been strongly linked to autism spectrum disorders (ASDs), suggesting that NMDARs are an important player in the beneficial effects observed with zinc in both animal models and children with ASDs. Significant evidence is emerging that these beneficial effects occur via zinc-dependent regulation of SHANK proteins, which form the backbone of the postsynaptic density. For example, dietary zinc supplementation enhances SHANK2 or SHANK3 synaptic recruitment and rescues NMDAR deficits and hypofunction in Shank3(ex13-16-/-) and Tbr1(+/-) ASD mice. Across multiple studies, synaptic changes occur in parallel with a reversal of ASD-associated behaviours, highlighting the zinc-dependent regulation of NMDARs and glutamatergic synapses as therapeutic targets for severe forms of ASDs, either pre- or postnatally. The data from rodent models set a strong foundation for future translational studies in human cells and people affected by ASDs.

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17. Luo T, Chen SS, Ruan Y, Chen HY, Chen YM, Li YM, Zhou W. Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway. Biochemical and biophysical research communications. 2023; 641: 168-76.

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe(2+), inhibited neuronal viability and downregulated GPX4 expression by inactivating the PI3K/Akt pathway. Ferroptosis inhibitors reversed the anti-survival effect of DDIT4, indicating that DDIT4 enhances ferroptosis through the PI3K/Akt pathway, thereby inhibiting neuronal viability. Further in vivo experiments found that autistic mice had high levels of ROS, MDA and Fe(2+), increased DDIT4 expression, and downregulated expression levels of GPX4, p-PI3K and p-Akt; after downregulation of DDIT4 expression, the accumulation of ROS, MDA and Fe(2+) was significantly reduced, while the expression levels of GPX4, p-PI3K and p-Akt were upregulated, indicating that DDIT4 knockdown reduces ferroptosis in autistic mice. In addition, DDIT4 downregulation, PI3K/Akt pathway activation, and ferroptosis inhibitors all improved social behavior deficits, repetitive stereotyped and compulsive behaviors, anxiety and exploratory behaviors in autistic mice, but PI3K/Akt pathway inhibitors significantly blocked the rescue of abnormal behaviors by DDIT4 downregulation in autistic mice. Therefore, downregulation of DDIT4 expression ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway, indicating that DDIT4, the PI3K/Akt pathway and ferroptosis have key roles in autism.

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18. Maksimović S, Marisavljević M, Stanojević N, Ćirović M, Punišić S, Adamović T, Đorđević J, Krgović I, Subotić M. Importance of Early Intervention in Reducing Autistic Symptoms and Speech-Language Deficits in Children with Autism Spectrum Disorder. Children (Basel, Switzerland). 2023; 10(1).

The intervention focused on starting treatment at an early age to develop the child’s full potential, which is known as early intervention. Given that autistic symptoms and language deficits occur at an early age and affect other areas of development in children with autistic spectrum disorder, we wanted to examine if early intervention is more effective in the reduction in autistic symptoms and language deficits in children aged 36-47 months old when compared to children 48-60 months old. The sample consisted of 29 children diagnosed with ASD who were admitted for integrative therapy. All participants were divided into two groups based on age: G1: 36-47 months old children, and G2: 48-60 months old children. To estimate the presence of autistic symptoms, we used the GARS-3, and for the assessment of speech-language abilities, we used the subscale Estimated Speech and Language Development (ESLD). Our results regarding the effect of the group on the difference in the scores at two time points showed that there was a statistically significant effect of the group on the reduction in autistic symptoms (p < 0.05) but no effect of the group on the differences in speech-language abilities between the two time points (p > 0.05). Our study highlights the importance of emphasizing the exact age when using the terms « early intervention » and « early development » in future studies and practice because it is necessary to determine and establish guidelines about which particular ages are crucial for starting treatment in certain developmental aspects.

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19. Noda Y, Fujii K, Mimura Y, Taniguchi K, Nakajima S, Kitahata R. A Case Series of Intermittent Theta Burst Stimulation Treatment for Depressive Symptoms in Individuals with Autistic Spectrum Disorder: Real World TMS Study in the Tokyo Metropolitan Area. Journal of personalized medicine. 2023; 13(1).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. While the symptoms of ASD are present from early childhood, there has been an increase in the number of adults with ASD in recent years who visit healthcare professionals to seek the treatment of depression due to maladjustment resulting from the core symptoms and are eventually diagnosed with ASD. Currently, no treatment is available for the core symptoms of ASD, and pharmacotherapy and psychotherapy are often provided mainly for secondary disorders such as depression and anxiety. However, the effectiveness of these therapies is often limited in individuals with ASD compared to those with major depression. In this context, neuromodulation therapies such as transcranial magnetic stimulation (TMS) have gained increasing attention as potential treatments. In this case series, we retrospectively analyzed 18 cases with ASD from the TMS registry data who had failed to improve depressive symptoms with pharmacotherapy and were treated with intermittent theta burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). We also explored the relationship between treatment efficacy and clinical epidemiological profile. Our results indicated that, despite the limitations of an open-label preliminary case series, TMS therapy in the form of iTBS may have some beneficial therapeutic effects on depressive symptoms in individuals with ASD. The present findings warrant further validation through randomized, sham-controlled trials with larger sample sizes.

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20. Orhan BE, Karaçam A, Özdemir AS, Gökçelik E, Sabuncu AA, Talaghir LG. Understanding the Families’ Perceptions of Adapted Physical Activity for Individuals with Autism Spectrum Disorder through Metaphors. Healthcare (Basel, Switzerland). 2023; 11(2).

The aim of this study was to understand the perceptions, understanding and experiences of the families of individuals with autism spectrum disorder (ASD) related to adapted physical activity (APA), and their educators, through their use of metaphors. The research was based on systematic content analysis in the qualitative research model. The data were collected based on metaphors. The participants included 85 families of individuals with ASD attending private institutions operating in Istanbul and Ankara. The metaphors used by the families were examined under two headings: adapted physical activities, and educators. When the metaphors used to describe APA were examined, four themes emerged, education, emotion, support and development, and these themes were divided into the categories of guidance, skill, affection, and care. When the metaphorical perceptions of educators were examined, three themes emerged: education, emotion, and social adaptation. These were further categorized as experience, knowledge, entertainment, independence, happiness, and treatment. The metaphors showed that experiences in APA support increased self-confidence for individuals with autism spectrum disorder and support the social adaptation of individuals who have the opportunity to apply knowledge and experience. This research shows that families have positive perceptions of APA educators and their lessons.

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21. Perzolli S, Bentenuto A, Bertamini G, Venuti P. Play with Me: How Fathers and Mothers Play with Their Preschoolers with Autism. Brain sciences. 2023; 13(1).

(1) Background: Children can develop cognitive and social skills during play. Most research has focused on mothers, but the paternal features in interaction with children with autism spectrum disorder (ASD) are mainly unexplored. This study aimed to compare fathers’ and mothers’ interactive behaviors with their children with ASD to identify similarities and differences during playful exchanges. (2) Methods: A total of 72 mothers and 72 fathers of paired children with ASD (chronological age: M = 44.61 months; SD = 13.37) took part in this study. Data were collected during 10 min of video-recorded semi-structured interactions with mothers and fathers separately in interaction with their children. (3) Results: Mothers showed more symbolic play (W = 3537; p < 0.001) than fathers, who displayed higher levels of exploratory play (t(139.44) = -2.52; p = 0.013) compared to mothers. However, child cognitive functioning impacts maternal play but not the father’s play characteristics. (4) Conclusions: Highlighting mother-child and father-child features may have important service delivery implications for implementing personalized parental-based interventions based on the strengths and weaknesses of both caregivers in a complementary system.

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22. Petazzi P, Jorge-Torres OC, Gomez A, Scognamiglio I, Serra-Musach J, Merkel A, Grases D, Xiol C, O’Callaghan M, Armstrong J, Esteller M, Guil S. Global Impairment of Immediate-Early Genes Expression in Rett Syndrome Models and Patients Linked to Myelination Defects. International journal of molecular sciences. 2023; 24(2).

Rett syndrome (RTT) is a severe neurodevelopmental disease caused almost exclusively by mutations to the MeCP2 gene. This disease may be regarded as a synaptopathy, with impairments affecting synaptic plasticity, inhibitory and excitatory transmission and network excitability. The complete understanding of the mechanisms behind how the transcription factor MeCP2 so profoundly affects the mammalian brain are yet to be determined. What is known, is that MeCP2 involvement in activity-dependent expression programs is a critical link between this protein and proper neuronal activity, which allows the correct maturation of connections in the brain. By using RNA-sequencing analysis, we found several immediate-early genes (IEGs, key mediators of activity-dependent responses) directly bound by MeCP2 at the chromatin level and upregulated in the hippocampus and prefrontal cortex of the Mecp2-KO mouse. Quantification of the IEGs response to stimulus both in vivo and in vitro detected an aberrant expression pattern in MeCP2-deficient neurons. Furthermore, altered IEGs levels were found in RTT patient’s peripheral blood and brain regions of post-mortem samples, correlating with impaired expression of downstream myelination-related genes. Altogether, these data indicate that proper IEGs expression is crucial for correct synaptic development and that MeCP2 has a key role in the regulation of IEGs.

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23. Rouphael M, Hojeij B, Ezzedine D, Mortada H, Sacre Y, Bitar T, Naim E, Hleihel W, Hoteit M. Assessment of Feeding Behaviors and Parents’ Frustrations of Children with Autism Spectrum Disorder in Lebanon: A Case-Control Study. Children (Basel, Switzerland). 2023; 10(1).

Children with autism spectrum disorder (ASD) exhibit restrictive and repetitive behaviors that affect their eating habits. The purpose of this study is to identify the behavioral feeding problems and eating habits among ASD children compared to typically developed (TD) children age/gender-matched controls, along with their parents’/caregivers’ strategies for dealing with them. It included 43 ASD children and 43 TD children aged two to eleven years. The analysis was performed based on two valid questionnaires: the Behavior Pediatrics Feeding Assessment Scale (BPFA) and « My Child Eating Habits » (MCEH). The BPFA and MCEH scores conceded three manifestations that fall into food selectivity and problematic mealtime behavior in both groups of children. Compared to TD children, children with ASD exhibited higher BPFA scores, which indicated food-related behavioral and skill-based problems (p = 0.004). Children with ASD were less likely to consume fruits, vegetables, and milk than TD children, which may lead to nutritional deficiencies (p = 0.003, p = 0.003, and p = 0.010, respectively). Parents of ASD children were concerned about their behavioral problems and expressed their intention of an early intervention. These findings highlight the importance of nutritional clinical routines that incorporate the evaluation of the nutritional status and feeding behaviors of ASD children.

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24. Singh R, Kisku A, Kungumaraj H, Nagaraj V, Pal A, Kumar S, Sulakhiya K. Autism Spectrum Disorders: A Recent Update on Targeting Inflammatory Pathways with Natural Anti-Inflammatory Agents. Biomedicines. 2023; 11(1).

Autism spectrum disorder (ASD) is a heterogeneous category of developmental psychiatric disorders which is characterized by inadequate social interaction, less communication, and repetitive phenotype behavior. ASD is comorbid with various types of disorders. The reported prevalence is 1% in the United Kingdom, 1.5% in the United States, and ~0.2% in India at present. The natural anti-inflammatory agents on brain development are linked to interaction with many types of inflammatory pathways affected by genetic, epigenetic, and environmental variables. Inflammatory targeting pathways have already been linked to ASD. However, these routes are diluted, and new strategies are being developed in natural anti-inflammatory medicines to treat ASD. This review summarizes the numerous preclinical and clinical studies having potential protective effects and natural anti-inflammatory agents on the developing brain during pregnancy. Inflammation during pregnancy activates the maternal infection that likely leads to the development of neuropsychiatric disorders in the offspring. The inflammatory pathways have been an effective target for the subject of translational research studies on ASD.

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25. Smith J, Rabba AS, Ali A, Datta P, Dresens E, Faragaab N, Hall G, Heyworth M, Ige K, Lawson W, Lilley R, Syeda N, Pellicano E. ‘Somali parents feel like they’re on the outer’: Somali mothers’ experiences of parent-teacher relationships for their autistic children. Autism : the international journal of research and practice. 2023: 13623613221146077.

Good relationships between parents and schools can improve autistic children’s school success. There are many reasons why families from different cultural backgrounds find it harder to develop good relationships with schools, such as language barriers, discrimination and unfamiliarity with education systems. We know little about what ‘good relationships’ look like for these families. Here, we worked with a team of autistic and non-autistic researchers as well as an Advisory Group of Somali parents to conduct interviews with 15 Somali mothers of kindergarten and school-age autistic children. We asked mothers about their experiences of their child’s education, communication with teachers and what a good relationship with schools would look like. We also asked how they felt the Somali community understood autism. We looked for common things that mothers said. We found that mothers were very proud of their children. They had high expectations, particularly about what children could do by themselves. Mothers found it frustrating that teachers had low expectations, that schools were not good at communicating with them and that autism-specific skills and experience were uncommon in schools. They also reported racist attitudes towards their children. Mothers experienced stigma and lacked resources, but support was gained from their daughters and their religion. Mothers themselves were proactively increasing community awareness and knowledge about autism in the hope that they and their autistic children would be valued and better supported. Our work has implications for how teachers and schools can work together with Somali parents to forge better futures for autistic children.

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26. Sulla F, Camia M, Scorza M, Giovagnoli S, Padovani R, Benassi E. The Moderator Effect of Subthreshold Autistic Traits on the Relationship between Quality of Life and Internet Addiction. Healthcare (Basel, Switzerland). 2023; 11(2).

People with sub-threshold autistic traits (SATs) are more prone to develop addictive behaviors such the ones linked to Internet abuse. The restrictions for anti-COVID-19 distancing measures encourage social isolation and, consequently, increase screen time, which may lead to Internet addiction (IA). However, a better quality of life (QoL) may have function as a protective factor against the development of IA. This study wanted to investigate the relation between SATs, QoL, and the overuse of the Internet in a group of 141 university students in the North of Italy. Participants completed a battery of tests. Results suggest that QoL is a predictive factor of IA and that the relationship between QoL and IA is significantly moderated by SATs. This could mean that SATs might represent a risk factor for IA, even when people have a better quality of life. Differences between female and male students are discussed, as well as possible implications for practice.

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27. Trajković J, Makevic V, Pesic M, Pavković-Lučić S, Milojevic S, Cvjetkovic S, Hagerman R, Budimirovic DB, Protic D. Drosophila melanogaster as a Model to Study Fragile X-Associated Disorders. Genes. 2022; 14(1).

Fragile X syndrome (FXS) is a global neurodevelopmental disorder caused by the expansion of CGG trinucleotide repeats (≥200) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. FXS is the hallmark of Fragile X-associated disorders (FXD) and the most common monogenic cause of inherited intellectual disability and autism spectrum disorder. There are several animal models used to study FXS. In the FXS model of Drosophila, the only ortholog of FMR1, dfmr1, is mutated so that its protein is missing. This model has several relevant phenotypes, including defects in the circadian output pathway, sleep problems, memory deficits in the conditioned courtship and olfactory conditioning paradigms, deficits in social interaction, and deficits in neuronal development. In addition to FXS, a model of another FXD, Fragile X-associated tremor/ataxia syndrome (FXTAS), has also been established in Drosophila. This review summarizes many years of research on FXD in Drosophila models.

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28. Turowetz J, Wiscons LZ, Maynard DW. Disorder or difference? How clinician-patient interaction and patient age shape the process and meaning of autism diagnosis. Sociology of health & illness. 2023.

This article follows Blaxter’s foundational call for a sociology of diagnosis that addresses the dual aspects of diagnosis-as-category and diagnosis-as-process. Drawing on video recordings from an autism clinic, we show how the process of attaching the diagnosis to a child involves interactions between clinicians, parents and children, and that in the course of such interactions, a diagnostic category officially defined in terms of deficits can instead be formulated in terms of valuable social and cognitive differences. More specifically, we show that the child’s age is crucial for how clinicians formulate the diagnosis: with younger children, clinicians treat autism exclusively as a deficit to be remedied, whereas with older children, clinicians may treat autism either as a deficit or as a social-cognitive difference. Further, because older children are often co-recipients of diagnostic news, we find that clinicians carefully manage the implications such news may have for their self/identity. Finally, we suggest that (1) the equation of a diagnostic category with dysfunction is achieved in interaction; (2) the meaning of a diagnosis may vary with characteristics of its recipients; and (3) that meaning can be worked up by clinicians and recipients in ways that centre difference rather than deficit.

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29. Turygin N, Matson JL, Adams H. Retraction notice to « Prevalence of co-occurring disorders in a sample of adults with mild and moderate intellectual disabilities who reside in a residential treatment setting » [Research in Developmental Disabilities 35/7 (2014) 1802-1808]. Research in developmental disabilities. 2023; 134: 104426.

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30. Vasilakis M, Polychronis K, Panagouli E, Tzila E, Papageorgiou A, Thomaidou L, Psaltopoulou T, Tsolia M, Sergentanis TN, Tsitsika AK. Food Difficulties in Infancy and ASD: A Literature Review. Children (Basel, Switzerland). 2022; 10(1).

PURPOSE: The aim of this literature review is to investigate the potential association between specific food difficulties and autism spectrum disorder (ASD) during the first two years of life. MATERIALS: The search was conducted in PubMed, Google Scholar, Embase and PsycInfo databases. RESULTS: Twenty-one studies were synthesized (3763 infants and children). Difficulties during breastfeeding, breast milk refusal and avoidance of taking solids have been linked to ASD. Infants with ASD have been referred to as picky eaters. Problematic mealtime behaviour during infancy has also been associated with ASD. CONCLUSIONS: The present review highlights the association between food difficulties, including problematic mealtime behaviours, food selectivity, breastfeeding difficulties and food refusal during infancy and ASD early during life, including the first months.

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31. Williams LN, Wieckowski AT, Dieckhaus MFS, Dai YG, Zhang F, Dumont-Mathieu T, Barton M, Fein D, Robins DL. Primary Care Clinician and Child Characteristics Impacting Autism Surveillance. Brain sciences. 2022; 13(1).

Early detection of autism provides access to early intervention and subsequently fewer lifelong challenges. However, disparities in screening have been associated with socioeconomic status (SES) and race, and disparities in surveillance have been associated with clinician knowledge and beliefs about autism identification. The present study examines associations between demographic variables and clinician beliefs, and agreement between screening results and clinician surveillance. Surveillance included activities used by the primary care clinicians (PCCs) to assess risk for autism. PCCs reported their beliefs about autism screening and identification, their sex, race, years in practice, and racial distribution of their patient population. Children’s demographic information was also collected. PCCs identified children as having, or not having, an increased likelihood of autism, and parents of children completed an autism screener. Agreement between screening and surveillance results were examined across PCC, practice, and child demographics. Higher confidence in autism knowledge and screening resources, female PCC sex, and majority White practice patient demographics all predicted agreement between screening and surveillance. Female child sex and higher maternal education also predicted agreement between screening and surveillance. These findings highlight the importance of PCC screening beliefs and child and PCC demographics on the autism identification process.

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32. Wongkittichote P, Chhay C, Zerafati-Jahromi G, Weisenberg JL, Mian A, Jensen LT, Grange DK. Novel LIAS variants in a patient with epilepsy and profound developmental disabilities. Molecular genetics and metabolism. 2023; 138(3): 107373.

Multiple mitochondrial enzymes employ lipoic acid as a coenzyme. Pathogenic variants in LIAS, encoding lipoic acid synthase (LIAS), are associated with autosomal recessive LIAS-related disorder (OMIM# 614462). This disorder is characterized by infantile-onset hypotonia, profound psychomotor delay, epileptic encephalopathy, nonketotic hyperglycinemia, and lactic acidosis. We present the case of a 20-year-old female who experienced developmental deficits at the age of 6 months and began to have seizures at 3 years of age. Exome sequencing revealed compound heterozygous novel variants in LIAS, designated c.277delC (p.Leu93Ter) and c.542A > T (p.Asp181Val). The p.Leu93Ter variant is predicted to cause loss of function due to the severe truncation of the encoded protein. To examine the p.Asp181Val variant, functional analysis was performed using Baker’s yeast (Saccharomyces cerevisiae) lacking LIP5, the homologue of human LIAS. Wild-type LIAS promoted oxidative growth of the lip5∆ yeast strain. In contrast, lip5∆ yeast expressing p.Asp181Val exhibited poor growth, similar to known pathogenic variants, p.Asp215Glu and p.Met310Thr. Our work has expanded the phenotypic and genotypic spectrum of LIAS-related disorder and established the use of the yeast model as a system for functional study of novel missense variants in LIAS.

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33. Xie Y, Wang H, Hu B, Zhang X, Liu A, Cai C, Li S, Chen C, Wang Z, Yin Z, Wang M. Dendritic Spine in Autism Genetics: Whole-Exome Sequencing Identifying De Novo Variant of CTTNBP2 in a Quad Family Affected by Autism Spectrum Disorder. Children (Basel, Switzerland). 2022; 10(1).

Autism spectrum disorder (ASD) affects around 1% of children with no effective blood test or cure. Recent studies have suggested that these are neurological disorders with a strong genetic basis and that they are associated with the abnormal formation of dendritic spines. Chromosome microarray (CMA) together with high-throughput sequencing technology has been used as a powerful tool to identify new candidate genes for ASD. In the present study, CMA was first used to scan for genome-wide copy number variants in a proband, and no clinically significant copy number variants were found. Whole-exome sequencing (WES) was used further for genetic testing of the whole quad family affected by ASD, including the proband, his non-autistic sister, and his parents. Sanger sequencing and MassARRAY-based validation were used to identify and confirm variants associated with ASD. WES yielded a 151-fold coverage depth for each sample. A total of 98.65% of the targeted whole-exome region was covered at >20-fold depth. A de novo variant in CTTNBP2, p.M115T, was identified. The CTTNBP2 gene belongs to a family of ankyrin repeat domain-containing proteins associated with dendritic spine formation. Although CTTNBP2 has been associated with ASD, limited studies have been developed to identify clinically relevant de novo mutations of CTTNBP2 in children with ASD; family-based WES successfully identified a clinically relevant mutation in the CTTNBP2 gene in a quad family affected by ASD. Considering the neuron-specific expression of CTTNBP2 and its role in dendritic spine formation, our results suggest a correlation between the CTTNBP2 mutation and ASD, providing genetic evidence for ASD spine pathology. Although the present study is currently insufficient to support the assertion that the de novo mutation M115T in CTTNBP2 directly causes the autism phenotype, our study provides support for the assertion that this mutation is a candidate clinically relevant variant in autism.

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34. Zappullo I, Conson M, Baiano C, Cecere R, Raimo G, Kirby A. The Relationships between Self-Reported Motor Functioning and Autistic Traits: The Italian Version of the Adult Developmental Coordination Disorders/Dyspraxia Checklist (ADC). International journal of environmental research and public health. 2023; 20(2).

BACKGROUND: We developed the Italian version of the adult developmental co-ordination disorders/dyspraxia checklist (ADC), providing reliability and concurrent validity data for the scale (Aim 1). In addition, we investigated the relationships between motor coordination difficulties and different autistic traits (Aim 2). METHODS: 498 participants (341 females; age range = 18-34) underwent the Italian version of the ADC, as well as a handwriting speed test, the autism spectrum quotient, the empathy quotient, and the systemizing quotient. RESULTS: The distinction between three main factors (A, B, and C) identified in the original version of the ADC was confirmed here. Internal consistency of the ADC subscales was adequate, as well as the correlation with the handwriting speed test used to assess concurrent validity. No substantial sex differences on the ADC scores were found. Furthermore, data revealed that poor autistic-related communication skills and lower levels of systemizing tendencies were, among all the investigated autistic traits, those more strongly associated with higher motor coordination difficulties. CONCLUSIONS: The Italian ADC seems a valuable tool for assessing motor coordination difficulties in adults and can reveal the nuanced impact exerted by different autistic traits on self-reported motor functioning.

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35. Zhang X, Shams SP, Yu H, Wang Z, Zhang Q. A Similarity Measure-Based Approach Using RS-fMRI Data for Autism Spectrum Disorder Diagnosis. Diagnostics (Basel, Switzerland). 2023; 13(2).

Autism spectrum disorder (ASD) is a lifelong neurological disease, which seriously reduces the patients’ life quality. Generally, an early diagnosis is beneficial to improve ASD children’s life quality. Current methods based on samples from multiple sites for ASD diagnosis perform poorly in generalization due to the heterogeneity of the data from multiple sites. To address this problem, this paper presents a similarity measure-based approach for ASD diagnosis. Specifically, the few-shot learning strategy is used to measure potential similarities in the RS-fMRI data distributions, and, furthermore, a similarity function for samples from multiple sites is trained to enhance the generalization. On the ABIDE database, the presented approach is compared to some representative methods, such as SVM and random forest, in terms of accuracy, precision, and F1 score. The experimental results show that the experimental indicators of the proposed method are better than those of the comparison methods to varying degrees. For example, the accuracy on the TRINITY site is more than 5% higher than that of the comparison method, which clearly proves that the presented approach achieves a better generalization performance than the compared methods.

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